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Biomedical subjects

E T Bloom

Publications and source records attributed to E T Bloom.

At least 73 records · Page 4Linked to original sources
PubMed1987

Life events, depressive symptoms, and immune function.

Because both bereavement and depression have been associated with impaired immune responses, the authors studied two indicators of immune function, natural killer (NK) cell activity and measures of T cell subpopulations, in 37 women who differed in the magnitude of recent life events. Women who had experienced major life changes had lower NK cell activity than women who had few changes. Severity of depressive symptoms in these women was associated with an impairment of NK cell activity, an absolute loss of suppressor/cytotoxic cells, and an increase in the ratio of T helper to T suppressor/cytotoxic cells.

Adult↗
PubMed1986

Monocyte-mediated augmentation of human natural killer cell activity: conditions, monocyte and effector cell characteristics.

The characteristics of the effector cells and monocytes, and conditions required for the monocyte-mediated augmentation of human natural killer (NK) cell activity were investigated. Enriched null cell populations were further fractionated by Percoll centrifugation and used as effector cells. The LGL-enriched fraction was less susceptible than either the unfractionated cells or the other Percoll fractions to the monocyte augmentation when mixed with monocytes in the chromium-release assay and when precultured with monocytes for 12 hr, retrieved by carbonyl iron treatment, and tested for NK activity against K562. This differential susceptibility was reflected at the single cell level. The LGL-enriched Percoll fraction did not display the increase in target-binding cells with lytic activity that was exhibited by the other effector cell preparations after culture with monocytes. No differences in Leu-7 and Leu-11 phenotypes were detected between enriched null cells that had been cultured with and without monocytes for 12 hr. At the monocyte level, it was shown that pretreatment of the monocytes with LPS did not alter their NK-augmenting activity appreciably. Glutaraldehyde-fixed monocytes were not effective, and actinomycin D-treated monocytes were less effective than untreated or irradiated monocytes when mixed with enriched null cells in the assay. Actinomycin D-treated monocytes did not augment and possibly suppressed NK activity tested after 12-hr culture, and irradiated monocytes were less effective for augmenting NK activity than untreated cells. Monocyte-mediated augmentation could be detected when the medium used for null cell-monocyte coculture was supplemented with a) different lots of fetal bovine serum, b) human AB serum, c) autologous serum, or d) no serum. Polymyxin B and indomethacin did not alter the monocyte effect. Finally, the monocyte-mediated augmentation of human NK was not MHC restricted, since allogeneic combinations were also effective. These results suggest that 1) lymphocytes other than LGL participate in the monocyte-mediated augmentation of NK activity, 2) the augmentation is probably activational rather than maturational, 3) the monocytes must be viable to be effective when mixed with null cells during the assay, 4) de novo RNA and/or protein synthesis by the monocytes is required for the monocytes to induce augmented activity in null cells after 12-hr coculture, 5) prostaglandin synthesis and endotoxin are probably not involved in the augmentation, 6) the phenomenon is not MHC restricted, and 7) monocytes may express augmentative and suppressive activities concurrently.

Adult↗
PubMed1986

Increased susceptibility of old mice to plasmacytoma induction.

Because multiple myeloma is a malignancy that appears in aging humans, the murine plasmacytoma model was selected to investigate the association between tumor formation, age, and immunity. Plasmacytomas were induced in young, middle-aged, and old BALB/c mice by intraperitoneal injections of pristane. Old mice were more vulnerable than middle-aged mice who were more vulnerable than young mice to histopathologically documented plasmacytoma formation. The difference between old and young mice was significant (p less than .05). The increased frequency of plasmacytomas was associated with decreased in vitro immune parameters in pristane-treated mice compared with age-matched saline-treated controls. The decrease was especially marked with T cell responses (mitogenic responses to concanavalin A, phytohemagglutinin, or allogeneic spleen cells) and natural killer (NK) cell activity. It was less striking with the predominantly B-cell parameters of mitogenic response to lipopolysaccharide (LPS) and LPS-induced plaque-forming cells. These findings support the hypothesis that old mice have increased vulnerability to plasmacytoma formation because of diminished NK and T cell activities.

Age Factors↗
PubMed1985

Monocyte-mediated augmentation of human natural cell-mediated cytotoxicity.

Normal human monocytes can significantly and rapidly augment natural cell-mediated cytotoxicity (NCMC) against K562 target cells. Approximately 50% augmentation was observed after direct mixture of monocytes with autologous null cells in the 4-hr chromium-release assay. This effect was dependent on the number of monocytes, and B cells and granulocytes were not effective. Coculture of null cells with monocytes and subsequent recovery of null cells for use as effector cells also produced significantly elevated cytolytic activity. This effect was dependent upon the number of monocytes, the length of time of coculture, and the cell donor. Augmentation of NK activity was rapid and observed after 0.5-12 hr of coculture, but suppression was observed after 36 hr; augmentation was observed with high monocyte:null cell (1:1, 1:2) ratios, and no effect was generally observed with lower ratios (1:8). At the single-cell level, the augmentation was associated with an increase in the proportion of target-binding cells which were lytically active. The augmentation of NK activity by monocytes required close cellular proximity, was mediated by a factor which was active or induced only in close proximity of the effector and producer cells, and/or was mediated by a soluble factor with a molecular weight greater than 50,000. This new demonstration that monocytes can augment as well as suppress NCMC may represent another avenue by which NK cell activity may be modulated in vivo.

Cell Communication↗
PubMed1985

Concentration-dependent augmentation of anti-K562 activity following short-term culture of null cell-enriched human blood lymphocyte populations.

The increase in natural cell-mediated cytotoxicity against K562 cells following short-term culture (e.g. 12 hours) of null cells was dependent upon the concentration of cells during incubation. The increased lytic activity by cells cultured at higher concentrations was associated with increased numbers of target-binding cells. It occurred with a variety of serum supplements in the medium. The augmentation of natural killer activity required close cellular proximity or contact and was not associated with detectable increased release of interferon or interleukin 2, although the participation of these molecules cannot be excluded. The lower recovery of lytic activity from cells incubated at lower concentrations was not associated with increased PGE synthesis.

Cell Communication↗
PubMed1983

Rapid kinetics of lysis in human natural cell-mediated cytotoxicity: some implications.

The entire lytic process of natural cell-mediated cytotoxicity against sensitive target cells can occur rapidly, within minutes. This was demonstrated by 51chromium release and in single-cell assays. At the cellular level, most of the target cell lysis occurred within 15-30 min after binding to effector cells. The enriched natural killer cell subpopulation of lymphocytes obtained Percoll density gradient centrifugation (containing greater than 70% large granular lymphocytes (LGL)) was the most rapidly lytic population by 51chromium release. However, in the single-cell assay, the rate of lysis of bound target cells was quite similar for the LGL-enriched effector subpopulation and the higher density subpopulation of effector cells recognized previously. Both the light and dense effector cells contained similar numbers of target binding cells. Therefore, that the light subpopulation effected lysis more rapidly and to a greater extent than the dense subpopulation suggested that the low-density effector cells probably recycled more rapidly than those of higher density. This was corroborated by the finding that when conjugates were formed at 29 degrees C for the single-cell assay, a significant number of dead unconjugated targets could be observed only on the slides made with the LGL-enriched effector cells but not on those made with dense effector cell. Lysis continued to increase in the chromium-release assay probably because of recycling, recruitment, and/or heterogeneity of the effector cells, and/or because of heterogeneity or delayed death of the target cells.

Chromium Radioisotopes↗
PubMed1983

Quantification of natural cytotoxicity by human lymphocyte subpopulations isolated by density: heterogeneity of the effector cells.

Natural cell mediated cytotoxicity has been expressed as percent cytotoxicity, as the slope of the titration curve obtained by testing different effector: target cell ratios, and as lytic units. Objections can be raised to each method as used. The present report involves the study of cytotoxicity by subpopulations of lymphocytes obtained by Percoll density gradient centrifugation. The subpopulations vary greatly in cytotoxic activity, making accurate comparisons by traditional means difficult. A method was therefore developed for making objective comparisons between activities of subpopulations of lymphocytes. Cytotoxicity titration curves, which were sigmoidal on linear-linear plots, were found to best fit the sigmoidal curves described by the Von Krogh equation. A best fitting scale family of curves having the identical maximum cytotoxicity and shape parameter was fitted simultaneously to cytotoxicity measurements obtained by titrating all subpopulations of effector cells obtained from each patient. Values expressing relative cytotoxicities were obtained from the ratios of the scale parameters of the different curves or by obtaining lytic units from the fitted curves. In addition to the enriched natural cytotoxic activity found among the lighter cells obtained by Percoll density gradient centrifugation, activity was also increased among cells sedimenting at the very bottom of the gradient. This was found in subpopulations of cells obtained from 16/21 gradients in tests against K562 and in subpopulations obtained from both of 2 gradients in tests against Daudi cells. These findings are consistent with the existence of at least 2 subpopulations of lymphocytes which can mediate natural cytotoxicity, and which are separable by density.

Cell Separation↗
PubMed1983

Natural cell-mediated cytotoxicity among A-bomb survivors residing in the United States.

Natural cell-mediated cytotoxicity (NCMC) by lymphocytes from Japanese atomic bomb survivors now living in the United States was measured. Seventy-one individuals were exposed to an estimated '0.00' Gy ('0 rads') (S0 group) and 58 to greater than '0.00 Gy' (S+ group) at the time of the bomb. Of this 58, 51 (88 per cent) received less than 0.50 Gy and 30 (52 per cent) received less than 0.10 Gy. NCMC was measured against 51Cr-labelled K562 target cells. Activity by lymphocytes from S+ group donors was significantly greater than that for the S0 group (p = 0.028 by the stratified Wilcoxon rank-sum test). This difference between the S+ and S0 populations was detected 35 years after exposure to the bomb. It is therefore feasible and important to examine appropriate biologic parameters to elucidate the effects of low doses of radiation in humans.

Aged↗
PubMed1983

Immune function in aging atomic bomb survivors residing in the United States.

Immunologic parameters were studied among survivors of the 1945 atomic bombs who now reside in the United States. Of all known survivors living in the U.S., about 40% (n = 189) participated in this study. Of those survivors on whom radiation exposure information was available (n = 168), 96% were exposed to less than 50 rad at the time of the bomb (ATB). Survivors were divided into two groups; those exposed to varying low doses of radiation (S+ group, exposed at less than or equal to 2500 m from the hypocenter) were compared with those exposed to "O rad" (S0 group, exposed at greater than 2500 m from the hypocenter). Of the former group, 92% were exposed to less than 100 rad and 89% to less than 50 rad ATB. Cellular immune responses, including natural cell-mediated cytotoxicity (NCMC), interferon production, and the mitogenic response to PHA, tended to be higher among S+ individuals, although only the difference for NCMC was statistically significant. This was suggestive of a trend which was consistent with the higher serum interferon levels and lower frequencies of detectable immune complexes and antimitochondrial antibodies among the S+ group, although these differences were not statistically significant. Other immunologic parameters which showed no trend included frequency of antinuclear antibodies, rheumatoid factor, levels of serum immunoglobulins, levels of isoantibodies and heteroantibodies, and the magnitude of the mixed lymphocyte reaction.

Adolescent↗
PubMed1981

Effector cells in natural cytotoxicity against human bladder cancer cell lines.

Human peripheral blood mononuclear cells obtained by ficoll-hypaque sedimentation were depleted of Fc-receptor-bearing (FcR+) cells. Cytotoxicity (direct killing of target cells by effector cells), tested in a 40 h assay, was significantly decreased against a variety of target cells. Tests in which no FcR+ cells could be detected were also positive for "natural killing" (NK) against a spectrum of target cells from normal donors. NK in this system was mediated by more than one subpopulation of lymphocytes. Monocytes probably did not play a significant role. Decreasing the FcR+ cells in peripheral blood mononuclear cells in patients with bladder cancer and in controls did not reveal specific antitumor activity.

Cell Line↗
PubMed1977

Antigen(s) on human transitional cell carcinoma detected by a xenogeneic antiserum.

In studies concerning human bladder cancer, antisera were raised in rabbits against human tumours, normal tissue, and cell lines derived from human tumours and were analysed by absorption and complement dependent microcytotoxicity tests. No significant selective cytotoxicity was discernible with any unabsorbed antisera. After absorption of A53, (an antiserum against the transitional cell carcinoma derived cell line T24) with peripheral blood cells and normal adult tissues, it was cytotoxic to two bladder cancer cell lines (T24 and J82) but not to four other cell lines. This activity was removed by absorption with each of two specimens of transitional cell carcinoma but not by normal bladder and by absorption with T24 or J82 but not with four other non-bladder cell lines. This functional specificity for transitional cell carcinomas could be due to a tumour associated antigen, a significant quantitative difference between tumour and normal cells, or an embryonic specificity re-expressed on the tumor. Further experiments are necessary to investigate these alternatives.

Absorption↗
PubMed1976

Disease and non-disease-related cell-mediated cytotoxicity in humans.

The human bladder cancer/T24 system was used to investigate disease and non-disease-related cell-mediated cytotoxicity (CMC). CMC was determined in a modification of the microcytotoxicity assay of Takasugi and Klein. Analysis of data of groups of patients confirmed previous findings that effector cells (EC) from bladder cancer patients were more cytotoxic against T24 than were EC from normal individuals or from patients with other genitourinary cancers. Differences between patients with bladder cancer and other patients were not observed for other target cells. During the course of these experiments, non-disease-associated CMC by EC from individual normal donors and patients was observed. This phenomenon was investigated to determine its reproducibility and its relationship to different methods of preparing EC. Reproducibility of non-disease-related CMC was ascertained using EC prepared from heparinized blood by centrifugation over Ficoll-Hypaque (FH). A total of 126 experiments were performed in which 18 normal donors were tested 2 to 7 times each against 4 target cell lines. Of the resulting 46 combinations or groups of repeated assays, only 7 showed significant variability. Each normal donor had consistent CMC with differences from others being reproducible. CMC was therefore not due to crowding or physical effects. CMC mediated by EC prepared in this manner was then compared to that mediated by EC prepared by other methods in simultaneous tests.

Cell Line↗