A-80 is a mucin-like glycoprotein associated with exocrine differentiation that shows little or no expression in normal exocrine cells and typical adenomas, but is upregulated in dysplasia and adenocarcinoma of certain organs. Its expression has not been systematically examined in prostatic adenocarcinoma and its putative precursor, prostatic intraepithelial neoplasia (PIN). The authors applied a mouse monoclonal antibody against A-80 in paraffin-embedded sections from 103 cases of prostatic carcinoma, 26 cases of nodular hyperplasia, 7 autopsy samples from normal young adult prostates, and 12 fetal prostates. All but one cancer reacted, although expression was heterogeneous; 75 of 103 stained extensively (> 3+ on a 0 to 5+ scale) and strongly. Staining extent and intensity were independent of tumor grade, and tended to be strong even when focal. Seventy-seven of 84 foci (92%) of high-grade PIN and 38 of 52 foci (73%) of low-grade PIN stained for A-80; reactions were most extensive and intense in high grade PIN. Only 5 of 26 cases (19%) of hyperplasia reacted, and this consisted of weak to moderate staining in sporadic cells; the remainder were negative. Normal adult prostatic epithelium did not express A-80 except for weak and inconsistent staining in foci of inflammation and infarction; atrophic glands were negative. Fetal prostate showed focally strong reactivity. These results indicate that A-80 is selectively expressed in most cases of intraepithelial neoplasia and prostate cancer, but is usually absent in benign and hyperplastic epithelium. The upregulation of glycoprotein A-80 in PIN and adenocarcinoma parallels observations in other organs, such as the breast and colon, suggesting that this is a significant oncodevelopmental molecule with potential clinical applications.

A murine monoclonal antibody designated 4B5 was raised against the high molecular weight fraction of pooled sputum from patients with non-small cell lung cancer [NSCLC]. Immunohistochemical staining indicated that 4B5 binds to histologically normal bronchial epithelium distant from tumor in 72% (39 of 54) of patients with NSCLC, but it binds to the primary cancer in only 13% [7 of 54] of the same patients. The antibody reacted less intensely with the bronchial epithelium in 16.6% [3 of 18] of autopsied patients without significant lung disease. The antigen recognized by 4B5 is a high molecular weight glycoprotein of more than 400 kilodaltons, judged by gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blot analysis. Antigenic activity persisted after heating and resisted treatment with neuraminidase, but it was destroyed using protease and periodate. Multiple epitopes were present on each molecule recognized by 4B5. The determinants recognized by this antibody deserve additional study as possible markers of premalignant change in patients with NSCLC.

Under the appropriate in vitro test conditions, intactE. coli strain K-12 was shown to be susceptible to the effects of platelet-derived β-lysin preparations. Enhanced β-lysin activity induced by variations in the initial log phase growth temperatures ofE. coli is presumed to be due to alterations in outer membrane fluidity. Treatment ofE. coli with ethylenediaminetetraacetate (EDTA) or ethyleneglycoltetraacetate (EGTA) appeared to promote enhanced outer membrane permeability, which was reflected by an increase in the susceptibility of EDTA- and EGTA-treated cells to platelet β-lysin. Restoration of outer membrane integrity was apparent when EDTA- or EGTA-treated cells were incubated in the presence of either CaCl2 or MgCL2 prior to β-lysin treatment and subsequently showed resistance to β-lysin bactericidal activity.

A solid phase assay for radiolabeled antibody synthesizedde novo in vitro has been described (1). The solid phase consists of antigen covalently bound to bromacetyl cellulose, a useful but difficult to prepare immunoadsorbent. Herein, we describe the preparation of polyamide resin immunoadsorbent and the procedure for coupling antigen to the polymer. Data are presented that show that polyamide resin-Ag‡ conjugates can replace bromacetyl cellulose-Ag conjugates. The usefulness of this easily prepared and inexpensive immunoadsorbent is discussed.

Keyhole limpet hemocyanin (KLH)-primed lymph node cell (LNC) populations were incubated with various amounts of KLH and the cellular incorporation of tritiated thymidine ([3H]TdR) or tritiated N6, O2′ dibutyryl cyclic AMP ([3H]DbcAMP) was determined. T LNC responded more vigorously than did complement receptor lymphocytes (CRL), i.e., B cells, at all KLH concentrations, during all time intervals examined, and in the presence or absence of normal rabbit serum (NRS). The depletion of adherent cells from KLH-primed LNC resulted in no significant decrease in KLH-induced incorporation of either [3H]TdR or [3H]DbcAMP in any of the LNC populations. Thus it appeared that variation among LNC populations in the incidence of macrophages did not account for the marked variation in their responses. Cultures containing equal numbers of T and CRL were induced to incorporate more [3H]TdR or [3H]DbcAMP than either population cultured separately or the sum of their individual responses. It was concluded that KLH-induced incorporation of these substances into primed, isolated LNC, was primarily manifested in the T-cell population. The synergism seen in cultures containing mixtures of T and CRL suggested that B cells are induced to incorporate [3H]TdR or [3H]DbcAMP in the presence of antigen and T-cell product(s). KLH-induced incorporation of [3H]TdR into KLH-primed LNC was inhibited by cholera enterotoxin (CT) and DbcAMP as previously reported. However, CT or DbcAMP inhibited this incorporation into T LNC to a greater extent than into CRL or unfractionated LNC.

The ultimate objective of the newer immunology is to understand various immune responses and reactions in cellular and molecular terms. The relevant molecules include various antigenic determinants, receptors and antigen-binding molecules on lymphocytic surfaces, molecules produced and secreted by lymphocytes, and lymphocytic surface molecules that recognize and are triggered by helper and/or regulatory molecules produced by other cells (Cold Spring Harbor Symposia, 1976). These cellular and molecular mechanisms have been illuminated by studies with hapten-protein and synthetic peptide systems in inbred strains of mice. Beginning in the early 1970’s Goodman utilized glucagon, Benjamini Tobacco mosaic virus protein and then Levy ferredoxin to obtain much new information about the relationships between antigenic structure of these proteins and their peptides and the capacity of these molecules to induce various immune reactions. We assumed that many questions about such relationships could be approached incisively with peptides derived from proteins of known molecular and antigenic structure. It was also hoped that the complexity of immune responses would be reduced by studying the results of adding single peptides to lymphocytes; this was based on the assumption that some of this complexity was due to the response of different clones of T and/or B lymphocytes to the different antigenic determinants on a protein. We proposed to utilize small peptides approximating in size one antigenic determinant, i.e., a tetrapeptide (Schechter et al., 1966) because such peptides would not effect the cross-linkage of receptors considered necessary for lymphocytic activation (Fanger et al., 1970).