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Biomedical subjects

E Klein

Publications and source records attributed to E Klein.

At least 577 records · Page 32Linked to original sources

Spleen-cell reactivity against transplanted neurogenic rat tumors induced by ethylnitrosourea: uncovering of tumor specificity after removal of complement-receptor-bearing lymphocytes.

Spleen cells from BDIX-rats bearing either GVlAl-tumor (a syngeneic mixed glioma) or NVlAc-tumor (a cloned syngeneic neurinoma of the peripheral nervous system) were cytotoxic to both tumor cells in vitro. However, the tumors displayed individually distinct antigenic specificities by in vivo rejection tests. Their in vitro cross-reactivity disappeared when a particular subpopulation of the spleen cells was used. The procedure of lymphocyte purification included three consecutive steps: treatment with carbonyl iron and magnetism, passage through a nylon wool column, and finally removal of complement receptor-bearing cells present in the colum-excluded population. Cross-reactivity between the syngeneic tumors persisted after the first two steps of lymphocyte purification. In contrast, specific cytotoxic reactions were observed against each individual tumor subsequent to the removal of the remaining C3 receptor-positive but surface Ig-negative cells. While killer cells were present in normal spleen-cell populations, these were almost completely eliminated by passage through the nylon wool column.

Animals↗

Human tumor--lymphocyte interaction in vitro: blastogenesis correlated to detectable immunoglobulin in the biopsy.

Binding of radioiodinated anti-immunoglobulin (Ig) reagent assayed by acid elutable radioactivity was shown in 18 of 44 cell suspensions (41%) prepared from surgical specimens of human tumors. Aliquots of these biopsies were admixed to autologous lymphocytes and in 13 cases they induced stimulation of DNA synthesis. In only one of these 13 cases was the anti-Ig reagent bound, while among the 26 biopsies with low or no binding capacity 12 (46%) were stimulatory, indicating that immunoglobulin-containing biopsies are not stimulatory. Experiments on 32 lymphocyte preparations from different lymphoid organs suggest that the immunoglobulin detected in the tumor-cell suspension is not derived from the infiltrating lymphoid cells.

Adolescent↗

Are methylcholanthrene-induced sarcoma-associated, rejection-inducing (TSTA) antigens, modified forms of H-2 or linked determinants?

TA3Ha/MSWBS hybrid cells have been derived from the fusion of the TA3Ha ascites carcinoma (H-2a) and the methylcholanthrene-induced MSWBS ascites sarcoma (H-2s). MSWBS expresses a strong tumor-specific transplantation antigen (TSTA), capable of inducing a rejection reaction in the syngeneic A.SW host. The genetic determinants of the H-2 complex are known to be localized on chromosome No. 17. TA3Ha contributes two normal, telocentric chromosomes No. 17 to the hybrid. In contrast, both chromosomes No. 17 of MSWBS are localized on readily identifiable translocations (17/1 and 17/M1 ; see Wiener et al., 1974). We have previously shown that the chromosomes No. 17 of one parental strain, or the other (but not both) can be removed from the hybrid by selective passage in the opposite parental strain. The present paper examined the possibility, often suggested in the literature, that the MC-sarcoma-associated TSTA could be a modified form of H-2. MSWBS, unselected TA3Ha/MSWBS and YACIR/MSWBS hybrids were compared with TA3Ha/MSWBS-derived isoantigen loss variants, with regard to their immunogenicity in the TSTA test, i.e. their ability to induce rejection of MSWBS target cells in ASW mice. Whereas the unselected hybrids were as immunogenic as the parental MSWBS line itself, two strain A compatible and two strain A.SW compatible variants which had lost chromosome No. 17 of the opposite strain showed a residual, but clearly weakened immunogenicity. Since there was no systematic difference between the reciprocal types, it is concluded that the genetic determinant of TSTA is not localized on the chromosome No. 17 but that a proper balance of this chromosome is required for the full expression of immunogenicity in the TSTA system.

Animals↗

In vitro "education" on autologous human sarcoma generates non-specific killer cells.

The cytotoxic effects mediated by lymphocytes from cancer patients after in vitro "education" on autologous tumor cells have been investigated. Peripheral blood lymphocytes from three sarcoma patients were cultivated on autologous tumor-cell monolayers and tested thereafter in a micro-cytotoxicity assay against tumor and fibroblast cells. This procedure led to the progeny of non-specific killer cells. As the phenomenon did not occur when the same lymphocytes were co-cultivated with autologous fibroblasts, the generation of non-specific effector cells may have been caused by specific antigenic triggering. The presence of autologous serum during "education" was found to inhibit the manifestation and/or the generation of killer cells. The same serum was without effect when added during the cytotoxicity assay only.

Antigen-Antibody Reactions↗

"Natural" killer cells in the mouse. I. Cytotoxic cells with specificity for mouse Moloney leukemia cells. Specificity and distribution according to genotype.

In the spleens of young, adult mice there exist naturally occurring killer lymphocytes with specificity for mouse Moloney leukemia cells. The lytic activity was directed against syngeneic or allogeneic Moloney leukemia cells to a similar extent, but was primarily expressed when tested against in vitro grown leukemia cells. Two leukemias of non-Moloney origin were resistant and so was the mastocytoma line P815. Although killer activity varied between different strains of mice, the specificity of lysis was the same as indicated by competition experiments using unlabeled Moloney or other tumor cells as inhibitors in the cytotoxic assays. Capacity to compete and sensitivy to lysis by the killer cells were found to be highly positively correlated. Analysis of the kinetics of the cytotoxic assay revealed a rapid induction of lysis within one to four hours, arguing against any conventional in vitro induction of immune response. No evidence was found of soluble factors playing any role in the cytolytic assay.

Animals↗

"Natural" killer cells in the mouse. II. Cytotoxic cells with specificity for mouse Moloney leukemia cells. Characteristics of the killer cell.

Normal mice contain cytolytic cells with specificity for in vitro grown mouse Moloney leukemia cells. Such killer cells are most frequent in the spleens; lymph node and bone marrow contain less and thymus virtually no killer activity. Peak activity is found around one to three months of age. Spleen cells from genetically athymic mice are as active killer cells as those from normal mice of the same strain. Treatment with anti-theta serum plus complement followed by removal of adherent and surface Ig positive cells by filtration through anti-Ig columns will leave between 1-5% of the original spleen cell population from a normal mouse. These cells have the morphology of small lymphocytes and perhaps contain all of the total original killer activity of the spleen against the Moloney leukemia cells. Such killer enriched cells are devoid of T and B lymphocytes and largely fail to function in antibody induced, cell-mediated lysis against antibody-coated chicken erythrocytes. It is concluded that the spontaneous selective cytotoxic activity of normal mouse spleen cells against Moloney leukemia cells is exerted by small lymphocytes of yet undefined nature.

Age Factors↗

The role of thymus on autosensitization against syngeneic normal and malignant cells.

Mouse lymphocytes were exposed to syngeneic fibroblasts and tumor cells in Millipore chambers inserted into the peritoneal cavity of intact and thymectomized mice. Autosensitization to fibroblasts occurred only if the chambers were carried by thymectomized mice. Sensitization to tumor-specific antigens also took place in intact mice. If thymic extract was administered to thymectomized mice autosensitization in the chambers was inhibited.

Animals↗

Surface markers on human B and T lymphocytes. VII. Rosette formation between peripheral T lymphocytes and lymphoblastoid B-cell lines.

Almost 100% of peripheral T lymphocytes are shown to have the capacity to form rosettes with human lymphoblastoid B-cell lines, predominantly at 4 degrees C and with lines having surface-bound IgG. Blast-transformed T cells retained this capacity and formed rosettes even at 37 degrees C. Unstimulated T cells bound less readily to B-cell blasts, stimulated by pokeweed mitogen for 72 hr. Even though rosettes, formed at 4 degrees C, were stable for several hours at 37 degrees C, no T-cell-mediated cytotoxicity could be detected during overnight incubation. Extreme pH values and trypsinization decreased rosette formation, whereas neuraminidase treatment enhanced the reaction. Rosette formation was independent of bivalent cations and unimpaired in the presence of inhibitors (NaF, NaN3), undiluted human or fetal calf sera, protein A, sonicated sheep erythrocyte membranes, and normal or heat-aggregated human IgG. Anti-Ig, anti-beta2-microglobulin, or anti-T cell sera did not influence rosette formation.

Animals↗

Sensitivity of volume of isoflow in the detection of mild airway obstruction.

The relative sensitivity of volume of isoflow test for detecting obstruction was compared to that of other tests, including flow at 60 per cent of total lung capacity, closing volumes, and frequency dependence of dynamic lung compliance. The volume of isoflow was measured in a waterless spirometer after 3 vital capacity inspirations of a mixture of 80 per cent oxygen. We studied 22 asymptomatic, healthy smokers (18 men and 4 women, 32.5 +/- 7.2 years of age, who smoked 5 to 20 pack-years). Thirteen smokers had an abnormal volume of isoflow, yet only 4 had an abnormal flow at 60 per cent of total lung capacity and 2 had an abnormal closing volume. Abnormal frequency dependence of dynamic lung compliance was demonstrated in 3 of 7 smokers tested with an abnormal volume of isoflow; none was detected in 7 smokers tested with normal volume of isoflow. Static pressure-volume curves and diffusing capacity were normal in all smokers with an abnormal volume of isoflow, and after bronchodilator inhalation, volume of isoflow improved in one half of the subjects. These results suggest reversible, intrinsic airway obstruction in the presence of normal flow at 60 per cent of total lung capacity and closing volume. Furthermore, volume of isoflow was a more sensitive test that flow at 60 per cent total lung capacity, closing volume, or frequency dependence of dynamic lung compliance.

Adult↗

Regression of cutaneous neoplasms following delayed-type hypersensitivity challenge reactions to microbial antigens or lymphokines.

Induction of delayed-type hypersensitivity challenge reactions to microbial antigens at sites of neoplasms involving the skin resulted in regression of mycosis fungoides, reticulum cell sarcoma, superficial basal cell carcinoma and adenocarcinoma of the breast. Similar reactions induced by lymphokine preparations also resulted in regression of lesions of mycosis fungoides and superficial basal cell carcinoma. The role of the large monomuclear cells in the inflammatory infiltrate of the delayed hypersensitivity reaction in eliciting the tumor regression is discussed. It is proposed that these large mononuclear cells represent the effectors in a primitive surveillance mechanism for neoplastic cells.

Adenocarcinoma↗