Robert J. Marder

Immunohistologic identification of phenotypic antigens associated with Hodgkin and reed‐sternberg cells. A paraffin section study

A combination of two monoclonal antibodies, designated LN‐1 and LN‐2, were used in an attempt to identify the corresponding antigens in Hodgkin and Reed‐Sternberg cells. The LN‐1 antibody has been shown in previous studies in our laboratories to identify follicular center cells, whereas LN‐2 marks certain B‐cell subpopulations as well as interfollicular histiocytes. Utilizing the perioxidase‐antiperioxidase (PAP) technique, paraffin‐embedded sections were examined representing 39 cases of various histologic subgroups of Hodgkins lymphoma following immunostaining with LN‐1, LN‐2, and the antibody to S‐100. Of these 39 cases, the LN‐2 antibody was found to consistently mark the majority of Hodgkin and Reed‐Sternberg cells. LN‐1 was found to identify Hodgkin and Reed‐Sternberg cells in a smaller number of cases. In no instance were Hodgkin or Reed‐Sternberg cells found to mark for the S‐100 protein. The use of LN‐1 and LN‐2 antibodies facilitated the identification of Hodgkin and Reed‐Sternberg cells and produced additional information regarding the phentotypic nature of these cells.

Maternal serum α-fetoprotein screening: Low and high values for detection of genetic abnormalities

In initiating a maternal serum alpha-fetoprotein screening program, we pursued not only elevated values for the detection of neural tube defects but also low values to detect trisomic fetuses. We detected neural tube defects (0.2%) as expected but were surprised by the efficacy with which low serum alpha-fetoprotein values identified aneuploid fetuses. In 1421 pregnant women, 132 (9.3%) showed maternal serum alpha-fetoprotein values less than 0.4 multiple of the median. After repeat sampling, 57 women still had low values. These 57 women and six others who were too anxious for repeat sampling underwent level I ultrasound examination with the following results: gestational age overestimated by 2 weeks (n = 8), fetal death (n = 1), and no explanation (n = 54). Of the 54, 49 underwent amniocentesis with detection of three aneuploid fetuses: trisomy 18 (n = 2) and trisomy 21 (n = 1); maternal ages were 27, 29, and 31 years, respectively. Autosomal aneuploidy did not occur in other women screened. We conclude that low maternal serum alpha-fetoprotein values could efficiently detect aneuploid fetuses, perhaps with greater sensitivity than previously predicted.

Low maternal serum α-fetoprotein and perinatal outcome

Abstract Pregnancy outcome was followed prospectively in women showing maternal serum α-fetoprotein values 0.05). Women with a viable pregnancy who show low maternal serum α-fetoprotein values have a more favorable prognosis than previously claimed.

Heterogeneity among the non‐Hodgkin's lymphomas. implications for autologous bone marrow transplantation with in vitro Purging using monoclonal antibodies

To investigate the possible implications of heterogeneity among the non‐Hodgkins lymphomas for bone marrow purging using complement‐fixing monoclonal antibodies to lymphoma‐associated antigens, a panel of large cell lymphoma cell lines of diverse phenotypes was treated with monoclonal antibodies DLC‐48 and LN‐1. An association was demonstrated between the percentage of suppression of colony formation by the cell line and both the percentage of cells staining with the antibody and the intensity of its binding. Flow cytometric analysis of cells surviving treatment with antibody and complement demonstrated that the population that escaped lysis showed weak immunofluorescent staining. Similarly, 40% of the clones derived from cells surviving treatment with antibody and complement stained weakly compared with the parent cell line. For a given fluorescence intensity, cells differed in their susceptibility to treatment. Some cells with moderate to strong staining survived incubation with antibody and complement. In five cases, treatment of bone marrow contaminated with malignant lymphoma cells resulted in complete eradication of even cells with weak staining. In two cases, a population of cells that stained dimly survived treatment with either antibody. DNA‐content analysis showed that the cell cycle distribution of cells surviving treatment with DLC‐48 or LN‐1 and complement was similar to that of cells treated with control antibody 46‐1G7 and complement. Phenotypic heterogeneity may hinder efforts to purge malignant lymphoma cells from human bone marrow with complement‐fixing monoclonal antibody reagents. Relative resistance to complement‐mediated lysis may underlie differences in the susceptibility of cells to treatment and also limit the effectiveness of this technique.

The elimination of malignant B lymphocytes from human bone marrow using monoclonal antibodies DLC-48 and LN-1 and human serum: A preclinical study

Monoclonal antibodies DLC-48 and LN-1 were evaluated for use in purging malignant lymphoma cells from human bone marrow. Using a 51Cr-release assay and sensitive clonogenic assay for the SU-DHL-2 and -4 cell lines, it was established that greater than four logs of malignant lymphoid cells can be eliminated from human bone marrow autografts with three treatments of antibody and autologous human serum at a final cell concentration of 1 X 10(7) cells/ml. A combination of DLC-48 and LN-1 was more effective than either antibody alone. Treatment with antibody and autologous serum had no effect on the growth of human hematopoietic progenitor cells. The clinical effects of marrow treatment with DLC-48 and LN-1 will be evaluated in upcoming clinical trials.