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D W Weiss

Publications and source records attributed to D W Weiss.

At least 37 records · Page 2Linked to original sources

Patterns of fibronectin deposition in normal and neoplastic fibroblasts and mammary tissue.

Deposition of fibronectin (FN) was studied by indirect immunofluorescent staining, employing monospecific rabbit anti-human FN antibody, in the following 3 systems: cultures of cells derived from Rous sarcomas of chickens and of normal chick fibroblasts; frozen sections of chicken Rous sarcomas; and frozen sections of mouse and human mammary tissue, normal and neoplastic. The normal fibroblasts produced a well-oriented, delicate, fibrillar FN network. The sarcoma cells in culture also formed a FN-positive matrix, but one very different in appearance, consisting of coarse, unoriented strands. FN was also present abundantly between the cells of the sarcomas in vivo. In normal mammary tissue, FN was localized predominantly in the basal lamina region, well delineated from the surrounding FN-reactive stroma. The epithelial cells were generally, but not always, FN-negative. In apparently normal tissue areas of the breasts of mammary carcinoma patients, epithelial cells with highly reactive cell peripheries were frequently seen; the stroma surrounding the positive cells was often poor in FN and the basal lamina region lacked the substance. Mammary carcinoma cells were almost always negative, but it was characteristic of these tumours that the surrounding stroma displayed FN richly.

Animals↗

Intralesional injection of interleukin-2-expanded autologous lymphocytes in melanoma and breast cancer patients: a pilot study.

The clinical effect of intralesional injection of interleukin-2 (IL-2)-cultured autologous lymphocytes was assessed in seven patients with cutaneous, recurrent tumor nodules (12 melanoma and 8 mammary cancer lesions). Each tumor nodule was injected 3-10 times, once weekly, with IL-2-cultured lymphoid cells (CLC), 40-400 million cells at each injection. Lymphoid cells obtained from buffy coats were separated on Ficoll-Paque, cryopreserved in liquid nitrogen, thawed, and cultured for 1-2 weeks in the presence of crude IL-2 (containing phytohemagglutinin) before injection. CLC were tested for sterility, percent E-rosette-forming cells, and cytotoxicity against K562, allogeneic melanoma, and breast cancer cell lines and autologous tumor cells. Enhanced cytotoxicity was expressed by IL-2 CLC, as compared with nonstimulated peripheral blood lymphocytes (PBL). Arrest of tumor growth (compared with untreated lesions) was observed in eight lesions and partial regression in three lesions. Moreover, complete regression was noted in one large melanoma lesion treated with low-dose irradiation prior to intralesional administration of CLC and in three small intracutaneous melanoma lesions treated with CLC only. Histopathological findings of responding lesions showed infiltration with lymphoid cells and macrophages, with the tumor cells sparsely dispersed. No untoward side effects of CLC injections were observed. The present study points to the feasibility of trials of adoptive immunotherapy in cancer patients as indicated by the following: (a) response of lymphoid cells to IL-2 adequate--although reduced--in patients with metastatic disease, including those after chemo- or radiotherapy; (b) possibility of cryopreservation of PBL and repeated culturing in IL-2 after thawing, with cytotoxic activity unimpaired; (c) demonstrably enhanced cytotoxicity in vitro of IL-2 CLC; (d) demonstrable--although limited--clinical response to in situ treatments with IL-2 CLC; (e) good tolerance of treatment with CLC.

Breast Neoplasms↗

Differential inhibition of contact sensitivity by suppressor T cells and suppressor factor induced by combined treatment with dinitrobenzenesulphonate and dinitrofluorobenzene.

Suppressor T cells acting on the efferent phase (Ts-eff) of dinitrofluorobenzene-contact sensitivity (DNFB-CS) were induced in BALB/c mice by injection of dinitrobenzenesulphonate (DNBSO3) and subsequent painting (sensitization) with DNFB. Ts-eff cells released a suppressor factor, antigen and strain specific, which was active in vivo in sensitized recipients. Administration of DNBSO3 alone generated suppressor T cells, which acted only on the afferent phase (Ts-aff). Suppressor T cells could not be detected in mice painted with DNFB and desensitized later by injection of DNBSO3.

Animals↗

Mouse macrophage functions under the influence of factors released by spleen cells preincubated with the methanol extraction residue (MER) tubercle bacillus fraction.

Exposure of mouse peritoneal macrophages in vitro to the nonspecific immunomodulator MER (methanol extraction residue fraction of phenol killed, acetone washed tubercle bacilli) failed to heighten their phagocytic and bacteriostatic activities toward Staphylococcus albus, even when amounts of the agent below the threshold of gross toxicity were employed. In contrast, exposure of such macrophages to supernatants of whole splenocyte suspensions that had been obtained from normal donors and were incubated with MER resulted in consistent potentiation of both phagocytosis and bacteriostasis. The findings suggest that the MER effect on macrophages function is mediated, in this system, by soluble lymphocyte product(s).

Animals↗

Cell-surface shedding by fibroblasts in culture.

The metabolic fate of cell-surface components was studied by labeling the surface of cultured chick embryo cells with [14C]glucosamine for 24 h, or by lactoperoxidase-catalyzed radioiodination. The cells were then cultured further in label-free medium for 24 h. At different time intervals thereafter, cells and culture medium were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The radioactivity profile of the metabolically labeled material in the medium was similar to that of the [125I]lactoperoxidase-labeled cells. The rate of disappearance of labeled macromolecular components from the cell surface was a mirror image of the rate of accumulation of these components in the medium. Analysis on 7 to 20% acrylamide gradient slab gel revealed that most of the labeled macromolecules in the medium comigrate with the surface micromolecules obtained from intact cells. It thus appears that at least some cell-surface components are shed in undegraded form. The possible biomedical implications of the detection of intact cellular membrane components in the circulation are discussed.

Animals↗

In vitro induction of cytotoxic effector cells against human neoplasms. I. Sensitization conditions and effect of cryopreservation on the induction and expression of cytotoxic responses to allogeneic leukemia cells.

Peripheral blood lymphocytes (PBL) from normal human donors were sensitized in vitro against allogeneic human acute myelocytic leukemia (AML) cells by means of an unidirectional mixed lymphocyte-tumor cell culture (MLTC) technique. The cytotoxic responsiveness of the sensitized lymphocytes, as determined in vitro by the 51Cr-release assay, varied among individual lymphocyte donors and was greatly dependent on the sensitization culture conditions. Induction of cytotoxic effector cells was augmented appreciably by adding to the cultures minute amounts of the immunopotentiating agent MER-BCG. Responding lymphocytes and stimulating leukemia cells cryopreserved for several weeks in liquid nitrogen were as effective as fresh cells in generating effector lymphocytes; the cytotoxic capacity of already sensitized lymphocytes was fully retained by cryopreservation. The implications of these findings for possible clinical employment of in vitro sensitized lymphocytes in adoptive immunotherapy of cancer are discussed.

Adult↗

Effect of the MER tubercle bacillus fraction on the responsiveness of mice to T-independent antigens.

The effect of treatment with the methanol extraction residue (MER) mycobacterial fraction on the immunological responsiveness of BALB/c mice to the T-independent antigens pneumococcal polysaccharide type III (SIIII) and trinitrophenyl-lipopolysaccharide conjugate (TNP-LPS) was ascertained. Pretreatment with MER prevented the establishment of immunological paralysis by threshold doses (10 or 15 microgram) of SIII and by a paralyzing dose of 100 microgram TNP-LPS. The induction of immunological paralysis by SIII was unaffected by treatment with the bacterial adjuvant Corynebacterium parvum and with the B cell mitogens PPD, LPS (Escherichia coli lipopolysaccharide), and dextran sulfate.

Animals↗

In vitro induction of cell-mediated immunity to murine leukemia cells. III. Effect of methanol extraction residue fraction of BCG on the generation of cytotoxic lymphocytes against leukemia.

Effects of the methanol extraction residue (MER) fraction of tubercle bacilli (BCG) on the generation of cytotoxic lymphoid cells were studied in vitro with the use of unidirectional mixed lymphocyte-tumor cell cultures. These cultures consisted of splenocytes of lymph node cells from normal donor C57BL/6, BALB/c, and strain A mice and mitomycin C-inactivated leukemia cells of both syngeneic and allogeneic origin. Addition of small amounts of MER (0.2-5 microgram/ml) to the cultures potentiated appreciably the elicitation of cytotoxic reactivity (as measured by the 51Cr-release assay) of the sensitized cells, whereas higher quantities (10-40 microgram/ml) had a strong suppressive effect. MER also induced some cytotoxic capacity in normal murine and human lymphoid cells not exposed to specific tumor cell stimulation. The stimulatory and suppressive effects were noted only when MER was present during the initial 24-48 hours of the 6-day culture. With the nylon wool fractionation technique, it was apparent that MER affected primarily the nonadherent cell population. MER could also prevent the generation of nonspecific suppressor cells by splenocytes maintained for 3-6 days in tissue culture.

Animals↗

Effects of prophylactic treatment with the methanol extraction residue fraction of tubercle bacilli (MER) on the development of Rous sarcomas of chickens following challenge with the Rous sarcoma virus.

Three-month-old chickens were treated with the methanol extraction residue fraction of tubercle bacilli (MER) under different conditions, and subsequently challenged with living Rous sarcoma virus. The birds developed progressively growing sarcomas following viral challenge. A substantial proportion of the hosts which had been pretreated with MER under optimal circumstances (38 to 58%) showed complete and long-lasting regression of the neoplasms, and the survival of many of the animals that did succumb to progressively growing tumors was prolonged. An absolute condition for prophylactic efficacy of MER treatment in this model system was injection of the agent into the same body area (wing) into which subsequent viral challenge was introduced. The quantity of MER employed and the timing of the prophylactic administration were also decisive variables.

Animals↗