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H F Pross

Publications and source records attributed to H F Pross.

48 records · Page 3Linked to original sources

Origin and partial characterization of Fc receptor-bearing cells found within experimental carcinomas and sarcomas.

A variety of murine connective and epithelial tissue tumors, including the SAD/2 and FS9 fibrosarcomas, the TA3/Ha and CAD/2 mammary carcinomas and a primary methylcholanthrene-induced sarcoma, were found to contain a high proportion of cells with receptors for the Fc portion of immunoglobulin G ("Fc receptors"). Experiments were undertaken to assess whether these cells were neoplastic, or whether they represented the infiltration into the tumor of non-malignant host cells such as macrophages or lymphocytes. It was found that long-term established in vitro cell lines of the TA3/Ha SAD/2 and CAD/2 tumors were entirely negative for the Fc receptor, whereas injection of these cells led to the formation of tumors containing a high proportion of Fc receptor-bearing cells. Many of these cells were actively phagocytic as assessed by ingestion of iron filings or antibody-coated erythrocytes. Injection of Fc receptor-negative cultured tumor cells into F1 hybrids, in which host cells could be distinguished from the tumor cells by anti-H2 sera, revealed that many or all of the Fc receptor-bearing cells in the resultant tumor were of host origin. In contrast to its effect on normal spleen cells, anti-theta serum treatment also partially inhibited Fc rosettes, suggesting a T-lymphocyte origin for some of the Fc receptor-bearing cells. Since almost all cells with potential anti-tumor activity bear Fc receptors, it is suggested that an index of host cell infiltration of carcinomas and sarcomas can quickly and easily be ascertained by enumeration of Fc receptor-bearing cells.

Animals↗

Cytotoxic lymphocytes from normal donors. A functional marker of human non-T lymphocytes.

A phenomenon we have termed spontaneous lymphocyte-mediated cytotoxicity (SLMC) by non-thymus-derived lymphocytes from normal donors has been described. The phenomenon can be demonstrated using human and xenogeneic (mouse) cell lines as the target cell in a microplate 51Cr release assay which is simple and reproducible. In this paper, SLMC against xenogeneic targets has been evaluated as a potential marker of lumphocytotoxic function with respect to: (a) the nature of the target cell; (b) the variability of the cytotoxic function of lymphocytes from different donors, and from the same donor tested on different days; (c) the nature of the effector cell. Using buoyant density centrifugation of iron plus magnetpurified lymphocytes forming rosettes with sheep red blood cells (SRBC) (T-cells) or SRBC-rabbit 19S anti-SRBC-mouse complement (complement receptor lymphocyte), it has been demonstrated that the cytotoxic activity lies in the non-T-lymphocyte fraction, and is probably caused by the complement receptor-bearing lymphocyte. The potential usefulness of this phenomenon as a functional marker of non-T-LYMPHOCYTE CYTOTOXIC Ability, and for the assessment of serological factors ehich may affect this cytotoxicity, has been discussed.

Animals↗

The immune response to sheep erythrocytes in the mouse. I. A study of the immunological events utilizing the plaque technique.

The direct and indirect plaque technique for the detection of antibody-forming cells against sheep erythrocytes was utilized for the investigation of a number of biological parameters of the primary and secondary immune response on a cellular level. The sequential pattern of 19S followed by 7S antibody formation was elicited in the primary response after a latent period of at least 1-2 days and 2-3 days respectively. The secondary response initiated 140 days after primary immunization, in contrast, was characterized by the simultaneous appearance of 19S and 7S antibody-forming cells after an observed latent period of 2-3 days. The cellular dynamics of the recruitment phase of the respective immunoglobulins in the primary and secondary response was interpreted as evidence for the derivation of the two classes of immunoglobulins from separate progenitors. The 19S antibody-forming cells were derived predominantly by a process of transformation and maturation and 7S antibody formers by a process of cellular division with a doubling time of about 12 hr. The draining lymph node exhibited maximal immunological reactivity due to its capacity to retain the particulate antigen. This capacity was considerably enhanced in the sensitized draining lymph node. Minimal cellular activity was also noted in distal lymphoid tissues which included the thymus. Focal cellular activity was observed in the draining lymph node for 60 days after immunization. Subsequently, very low level plaque-forming cellular activity was observed in association with persistence of maximal antibody activity. The appearance at 120 days of a generalized peak of cellular activity in lymphoid tissues throughout the host was considered an explanation for this discrepancy. The change in distribution of cellular antibody-forming activity, from a local to a generalized lymphatic response during the late phase of the immune response, implied a fundamental alteration in homeostatic mechanisms associated with maintenance of immune reactivity. Further manifestations of such an alteration were indicated by the appearance of 2-ME-sensitive 7S antibody nearly 3 months after primary intradermal immunization, which in the ensuing 5 months was associated with, and inversely related to, two major fluctuations in 2-ME-resistant 7S antibody. Evidence for the existence of immunological memory in the 19S system was not established in the present work. 19S anamnesis, for which evidence was derived from measurements of circulating antibody levels, was interpreted from cellular studies as the result of the substantial activity of previously uncommitted 19S lymphoid cells in distal lymphoid tissue associated with previously committed 19S cells contained in the draining lymph node.

Animals↗

P-glycoprotein-mediated multidrug resistance and cytotoxic effector cells.

Multidrug resistance (MDR) is one of the major obstacles to successful cancer chemotherapy. MDR is a complex and multifactorial phenomenon. One important and common mechanism used by cancer cells as a defense against cytotoxic drugs is a 170-kD plasma membrane glycoprotein, P-glycoprotein (P-gp). P-gp confers resistance by actively pumping cytotoxic drugs out of cancer cells. Paradoxically, P-gp overexpression on tumor cells is frequently associated with enhanced susceptibility to lymphokine-activated killer cell activity. This enhanced susceptibility is not observed with P-gp- MDR cells, nor is susceptibility to natural killer cells increased. The physiologic, evolutionary and immunologic concepts with regard to the P-gp and the possible intervention of the function of the P-gp in cancer therapy are reviewed.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Peripheral blood mononuclear cells express antigens associated with multidrug resistance in a small cell lung cancer cell line.

H69AR is a multidrug resistant small cell lung cancer (SCLC) cell line that does not overexpress P-glycoprotein, the plasma membrane drug efflux pump usually associated with this type of resistance. Monoclonal antibodies (MAbs) were previously raised against H69AR cells, and three of these MAbs, 2.54, 3.50, and 3.186, cross-reacted with peripheral blood mononuclear cells. T cells (CD3+), B cells (CD19+), NK cells (CD16+) and monocytes (CD14+) expressed each of the three antigens, but to differing degrees. Immunoprecipitation and partial proteolytic mapping experiments demonstrated that the antigens detected by MAbs 2.54 and 3.186 are identical in H69AR cells and PBMCs. SCLC cells are known to express many hematopoietic antigens; however, this is the first report of SCLC multidrug resistance-associated antigens being expressed on hematopoietic cells.

Antibodies, Monoclonal↗

Role of natural killer cells in cancer.

This paper reviews recent publications and presents data dealing with natural killer (NK) cell activity in the tumor-infiltrating lymphocytes (TIL) and peripheral blood (PBL) of patients with solid tumors and leukemia. Cells with NK markers or function are not a prominent feature of lymphoid infiltrates in solid tumors and, when present, do not appear to correlate with other prognostic variables. Nevertheless, NK cells among IL-2-activated TIL mediate antitumor cytotoxicity. Many studies indicate that NK activity is reduced in patients with advanced cancer. In some of these studies, low NK activity has been shown to be an unfavorable prognostic variable. PBL, splenic and bone marrow NK activity in patients with acute myelogenous leukemia (AML) is also decreased. However, adherent IL-2-activated lymphocytes composed primarily of NK cells were found to be cytotoxic against AML blasts and could be generated from patients in remission and relapse. The question of whether low NK activity in solid tumors and leukemia is the result of the disease state or contributes to it, remains unanswered. Data are also presented here showing that treated, apparently disease-free patients with high PBL NK activity have a significantly longer metastasis-free survival time than those with low NK activity (n = 91, p < 0.026, Cox proportional hazards test).

Cytotoxicity, Immunologic↗

Lymphokine-activated killer cell susceptibility and multidrug resistance in small cell lung carcinoma.

Intrinsic or acquired resistance to anticancer drugs necessitated the search for different treatment modalities. The sensitivity of tumor cells to lysis by natural killer (NK) and lymphokine-activated killer (LAK) cells was studied in multidrug resistant (MDR) small cell lung carcinoma (SCLC) by 51Chromium (51Cr) release and conjugate formation assays. The following observations were made: P-glycoprotein positive (P-gp+) MDR SCLC cell line variants were lysed by human LAK cells to a greater extent than were their drug sensitive counterparts. In contrast, P-gp, multidrug resistance protein positive (MRP+) variants of the same line did not exhibit an increased susceptibility to LAK cells. Differential LAK susceptibility is not due to a generalized increase in target fragility to cellular immunity, because NK sensitivity was not increased. Moreover, the P-gp+ MDR SCLC cells showed a higher frequency of binding to LAK cells than did the drug-sensitive parental line. These observations may lead to new insights on combining chemotherapy with immunotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗