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Biomedical subjects

M Towle

Publications and source records attributed to M Towle.

8 recordsLinked to original sources
PubMed1990

Retroviral mediated transfer and expression of exogenous genes in primary lymphoid cells: assaying for a viral transactivator activity in normal and malignant cells.

In this report we describe the use of recombinant retroviruses to characterize the activity of an exogenous promoter in primary cells obtained from patients with lymphoproliferative disorders. The infection of a variety of cultured and primary lymphoid cells with a recombinant retrovirus containing a histone promoter-driven beta-galactosidase gene is shown to result in the expression of beta-galactosidase in 50% to 100% of the cells. A similar infection with a recombinant retrovirus containing the beta-galactosidase gene with an adenovirus E2 promoter, results in beta-galactosidase activity in a limited number of cultured and primary cells. Since the adenovirus E2 promoter has been well characterized and is known to be regulated by transactivators encoded by many viruses, the activity of this promoter in specific cell types is discussed in reference to both the biology of the cell and the possible presence of as yet undetected viral gene products.

Adenovirus Early Proteins↗
PubMed1990

Retroviral mediated gene transfer into bone marrow progenitor cells: use of beta-galactosidase as a selectable marker.

Recombinant retroviruses have been utilized as vectors for gene transfer in model systems of gene therapy. Since many of these model systems require the transplantation of genetically modified primary cells it is important to devise methods which will allow the rapid and efficient selection for transplantation of only the cells which are capable of expressing high levels of the transferred gene. This report describes the use of beta-galactosidase as such a selectable marker. Bone marrow progenitors are infected with a recombinant retrovirus encoding beta-galactosidase. Using a fluorescence assay for beta-galactosidase we demonstrate that it is possible to use cell sorting to enrich for cells which will form bone marrow colonies that express high levels of beta-galactosidase. This rapid and non-toxic selection of bone marrow cells may facilitate attempts to achieve gene therapy in a variety of model systems.

Animals↗
PubMed1984

Circulating monoclonal B lymphocytes in non-Hodgkin's lymphoma.

Using a sensitive flow cytometric method ("kappa-lambda analysis"), we have found monoclonal B lymphocytes in the blood of 71 of 91 patients with non-Hodgkin's lymphoma. The presence of the B lymphocytes was independent of the histologic subclassification of the patient's disease. When we performed simultaneous analysis of the surface light-chain type in tumor tissue obtained by biopsy, the apparent light-chain type of the blood monoclonal cells corresponded with that of the tumor in 21 of 23 patients (P = 0.03). There was no correlation of the presence of these cells in the blood with morphologic evidence of bone-marrow involvement by lymphoma, but there was a strong correlation with clinical staging. Studies performed during prolonged clinical remission showed that whereas 16 of 25 patients with nodular non-Hodgkin's lymphoma had persistence of monoclonal lymphocytes, none of the 14 patients with diffuse histiocytic lymphoma in remission had these findings (P less than 0.005). Our analysis for B-cell clonal excess demonstrates the persistence of circulating monoclonal lymphocytes during complete remission in patients with forms of lymphoma that have a high probability of relapse, but we did not find these cells in patients in remission from categories of lymphoma in which prolonged remission is associated with cure. It is possible that the circulating monoclonal lymphocytes in patients with lymphoma are malignant cells, and their disappearance or persistence after remission may have prognostic importance.

B-Lymphocytes↗
PubMed1981

Human B lymphocyte subsets. I. IgG-bearing B cell response to pokeweed mitogen.

The subset of B lymphocytes having IgG on their surfaces was purified from human spleen and blood using a fluorescence-activated cell sorter (FACS). This subset constituted about 15% of B lymphocytes. The remaining non-IgG-bearing B cells were also obtained for study. These two populations were examined for (a) their expression of other surface immunoglobulin isotypes, (b) their ability to give rise to IgG- and IgM-secreting (plaque-forming) cells in a pokeweed mitogen (PWM)-driven culture system, and (c) their ability to proliferate in response to PWM stimulation. The results of these studies indicate that most IgG-bearing B cells also express surface IgM and IgD. Less than 15% had only IgG. The IgG-positive cell gave rise to both IgG and IgM plaque-forming cells when driven by PWM, and in fact were responsible for most of the total plaque response in both the IgG and IgM classes. The non-IgG-bearing B cells were depleted of both IgG and IgM responsiveness. The failure of the non-IgG-bearing B cells to give a strong response to PWM did not appear to be due to either depletion of accessory cells or to any suppressive influence. Finally, proliferation studies indicated that both the IgG-bearing and the non-IgG-bearing cells proliferated in the presence of PWM with a somewhat stronger proliferative response in the IgG-bearing cells. These results demonstrate that the IgG-bearing cell is not irreversibly committed to IgG production but can also give rise to IgM-secreting cells, and that human PWM-driven immunoglobulin secretory responses are predominantly due to a numerically small subset of B cells.

B-Lymphocytes↗