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Biomedical subjects

T Hoffman

Publications and source records attributed to T Hoffman.

At least 109 records · Page 6Linked to original sources
PubMed1983

Interferon-induced differentiation of U937 cells. Comparison with other agents that promote differentiation of human myeloid or monocytelike cell lines.

Effects of human fibroblast (beta) or leukocyte (alpha) interferon (IFN) on differentiations of a human histiocytic lymphoma-derived cell line (U937) or promyelocytic leukemia-derived cell line (HL-60) were studied. When cultured with beta-IFN (400-1,000 U/ml), U937 cells showed gross morphologic and microscopic changes consisting of clumping, increased cytoplasmic-to-nuclear ratio, enhanced prominence of cytoplasmic granules, and membrane ruffling. After culture with beta-IFN, the number of U937 cells reactive with B43.4.1 monoclonal antibody, which is specific for human monocytes, natural killer cells, and neutrophils, increased from less than 10% of U937 cells to 47% beta-IFN treatment also enhanced antibody-dependent cellular cytotoxicity against chicken erythrocytes by U937 cells. The same morphologic, phenotypic, and functional changes were also observed when U937 were treated with recombinant or natural alpha-IFN. The effects of alpha-IFN were totally abolished by anti-alpha-IFN serum. In contrast, HL-60, which differentiates toward cells of the monocyte lineage in response to phorbol 12-myristate 13-acetate (based on the above criteria), and toward granulocytes in response to dimethyl sulfoxide, did not differentiate when cultured with alpha- or beta-IFN. No consistent relationship between induction of differentiation and changes in phospholipid methylation were observed.

Antigens↗
PubMed1983

Augmentation of human peripheral blood natural killer activity by methisoprinol.

Methisoprinol (MIP) was found to augment natural killer (NK) activity of peripheral blood mononuclear cells (PBMC), as measured in a 4-h 51Cr release assay using K562 cells as targets. Overnight incubation of PBMC with 0.1 microgram/ml MIP, followed by removal of the drug, resulted in significant increases in the NK activity of all 17 donors studied. Augmentation of NK, expressed as lytic units (LU)/10(7) effector cells, was generally two- to fourfold, and was manifest as early as 1 h after incubation with the drug, but was maximal after 4 h. The effect of MIP was dose dependent up to 0.1 microgram/ml and remained at a plateau up to 10 micrograms/ml, where cytotoxicity to the effectors was observed. The effect of MIP was exerted on the effector cells and was not due to an increased susceptibility of target cells to lysis. In addition, this phenomenon was probably independent of interferon (IFN) production. Binding and killing at the single-cell level were shown to be unaffected by prior treatment with MIP. Rather, the analysis of the kinetics of NK activity indicated that MIP increased the recycling ability of NK effector cells. Augmentation of NK by MIP was dependent on the presence of adherent cells in PBMC fractions. Populations depleted of plastic adherent cells or populations enriched for adherent cells themselves could not undergo boosting by MIP, indicating that MIP did not act to recruit functional cells from inactive precursors. These studies suggest that the observed antiviral and/or immunoregulatory actions of MIP might be mediated through an increased NK cell activity.

Cell Adhesion↗
PubMed1983

Inhibition of human natural killer (NK) activity and antibody dependent cellular cytotoxicity (ADCC) by lipomodulin, a phospholipase inhibitory protein.

A highly purified preparation of lipomodulin, a phospholipase-inhibitory protein from rabbit neutrophils treated with glucocorticoids, inhibited NK and antibody-dependent cellular cytotoxicity (ADCC) activities of human peripheral blood lymphocytes in a dose-dependent manner. The presence of lipomodulin during the early period of the cytotoxicity assay was necessary to obtain maximal inhibition. The inhibition of NK or ADCC activity by lipomodulin was greater when effector cells were treated with lipomodulin than when target cells were incubated with lipomodulin. As lipomodulin did not block binding of effector cells to target cells, our results suggest that lipomodulin inhibits the cytolytic phase of NK and ADCC activities after binding to target cells, and imply that phospholipase(s) may be involved in NK and ADCC activities.

Annexins↗
PubMed1983

Activation of human monocyte cytotoxicity by natural and recombinant immune interferon.

Human T cell hybridomas were established by fusion of SH9 cells, the 6-thioguanine-resistant mutant line of human T lymphoma Hut 102-B2, with concanavalin A-stimulated human peripheral blood lymphocytes. Hybridoma line L38 produced a macrophage activating factor (MAF) with the ability to activate human peripheral blood monocytes to show enhanced cytotoxicity against human colon adenocarcinoma HT-29 cells in a 72-hr 125iododeoxyuridine-release assay. The L38 line was then cloned by the limiting dilution technique and two sublines, L38B and L38D, were found to produce high levels of MAF constitutively. Interferon activity was also detected in L38B and L38D supernatants. When interferon activity was neutralized with specific antiserum to purified human immune interferon (IFN-gamma), MAF activity was abrogated. To confirm that the MAF activity is indeed due to IFN-gamma, IFN-gamma was purified from the culture supernatant of another human T cell hybridoma, L265K2, a cell line known to produce high levels of IFN-gamma. Two highly purified IFN-gamma fractions with m.w. of 20,000 and 25,000, respectively, were obtained by NaDodSO4/polyacrylamide gel electrophoresis (SDS-PAGE). Similar fractions were obtained from IFN-gamma derived from human peripheral blood lymphocyte (PBL) cultures induced with 12-0-tetradecanoylphorbol-13-acetate (TPA) and phytohemagglutinin (PHA). In comparison, Escherichia coli-derived recombinant human IFN-gamma separated by SDS-PAGE yielded two major active fractions with m.w. of 17,000 and 34,000. With all three types of preparations, a close correlation was found between the presence of IFN-gamma activity demonstrable in an antiviral assay and MAF activity in individual fractions. Substantial quantitative differences were observed in the ability of various human IFN to activate monocytes. Although no MAF activity was detected with IFN-alpha and IFN-beta at concentrations up to 200 U/ml, both natural and recombinant IFN-gamma showed marked MAF activity at concentrations as low as 0.3 to 1 U/ml.

Antigens, Surface↗
PubMed1982

Effect of interferon on phospholipid methylation by peripheral blood mononuclear cells.

The effect of human interferon (IFN) preparations on the metabolic pathway leading to the synthesis of phosphatidylcholine (PC) by a stepwise addition of methyl groups to phosphatidylethanolamine (PE) was investigated in human peripheral blood mononuclear (PBMN) cells. An inhibition of the synthesis of PC via this pathway was regularly observed with both alpha- (recombinant or natural) and beta-IFN. This inhibition was apparent within the first 5 min of treatment, reached its maximum between 15 min and 1 hr, and persisted at the same level until 6 hr, the last time point examined. Each of the transmethylated products of PE underwent a similar inhibition, as measured by the turnover rate of individual products. The intracellular pool of the methyl donors, methionine and S-adenosyl-methionine (SAM), was shown to be unaffected. The methyltransferase activity of IFN-pretreated cell extracts was unchanged. These findings support the hypothesis that IFN induces a functional change in phospholipid methylation at the level of organized membrane-bound phospholipid methyltransferase enzymes in intact cells.

Cell Membrane↗
PubMed1981

Phospholipid methylation and phospholipase A2 activation in cytotoxicity by human natural killer cells.

The role of phospholipid methylation and phospholipase A2 (phosphatide 2-acylhydrolase, EC 3.1.1.4) in natural killer (NK) function by human peripheral blood mononuclear cells was studied. Pretreatment of effector cells with a methyltransferase inhibitor, 3-deazaadenosine, in the presence of homocysteine thiolactone, reduced cytotoxicity in a dose-dependent fashion. This effect was closely associated with inhibition of methylation of lipids but not of nucleic acids or proteins. The suggestion for a role of phospholipid methylation was supported by the observation that the interaction between NK-susceptible tumor targets and peripheral blood mononuclear cells caused increased phospholipid methylation only when susceptible target cells were used. Phospholipase A2 was also implicated in human NK activity. Inhibitors of the enzyme such as tetracaine, mepacrine, Rosenthal's inhibitor, and corticosteroids impaired NK function. Rosenthal's inhibitor was also shown to exert an inhibitory effect on a purified NK-cell population obtained by the isolation of large granular lymphocytes on Percoll gradients. Peripheral blood mononuclear cells were also directly shown to display phospholipase A2-like activity, as measured by the decrease in radioactive arachidonate from prelabeled phospholipids, specifically phosphatidylcholine, in effector cells. These data suggest that enhanced phospholipid methylation occurs during the recognition function of NK cells. Consequent activation of phospholipase A2 might be involved in the mechanisms leading to lytic events within the target cell.

Adrenal Cortex Hormones↗
PubMed1980

Natural killer funciton in systemic lupus erythematosus.

Peripheral blood lymphocytes from patients with systemic lupus erythematosus (SLE) demonstrated significantly less cytotoxicity against two different lymphoblastoid cell lines and one myeloid cell line than peripheral blood lymphocytes from normal individuals. Short-term culture and other attempts to remove interfering immune complexes failed to restore low natural killer (NK) function. Six day culture in fetal calf serum resulted in increased cytotoxicity by mononuclear cells from normal individuals and some SLE patients, but this effect was shown to be dependent on Fc-, not Fc+, effector cells. Suppressor cells were not demostrable as a cause for decreased NK activity.

Antigen-Antibody Complex↗
PubMed1980

Enzyme-linked immunosorbent assay for screening monoclonal antibody production: use of intact cells as antigen.

An enzyme-linked immunosorbent assay (ELIZA) was developed for screening production of monoclonal antibodies with specificity for surface membrane components on human mononuclear cells. Whole cells used as antigen were desiccated under vacuum in flexible polyvinyl chloride plates or in rigid plates coated with protein-detergent solution. Rabbit or goat anti-mouse IgG conjugated with peroxidase was used as indicator after affinity column purification. Under these conditions, the sensitivity of ELISA proved comparable to other binding techniques or microcytoxicity and allowed rapid, reproducible, and efficient detection of antibody producing hybridomas.

Animals↗
PubMed1979

Single or combination therapy of staphylococcal endocarditis in intravenous drug abusers.

Staphylococcus aureus is the commonest cause of acute endocarditis in intravenous drug abusers. In-vitro and in-vivo animal studies have found increased killing of organisms with the combination of a beta-lactam antibiotic and an aminoglycoside. These findings have created a controversy about the use of such combination therapy. We randomly treated 25 episodes of S. aureus endocarditis in intravenous drug abusers with either single or combination antibiotic regimens. Mean days to defervescence were similar in both groups: 6.3 d (SEM, 1.49 d) for the single drug group and 6.6 d (SEM, 1.02 d) for the group treated in combination with an aminoglycoside. There were no bacteriologic failures or relapses in either group. No patients needed valvular surgery, and the mortality rate was zero. Thus, it appears that single drug therapy with an appropriate beta-lactam antibiotic is adequate and appropriate in intravenous drug abusers with S. aureus endocarditis.

Adult↗
PubMed1979

Comparison of various tests for Fc receptors on different human lymphocyte sub populations.

Six different immune complex test systems for the detection of IgG Fc receptors were applied to the study of various human lymphocyte populations. The extent of binding varied widely according to the system and the cell type employed. Two systems bound preferentially to a high proportion of B lymphocytes from peripheral blood or tonsils, one of which bound with only a very few T cells. In contrast, four other test systems which bound well with the Fc receptors on T lymphocytes gave weaker reactions with Fc receptors on B cells. The reactivity of Fc receptors on null or third population lymphocytes was similar to that of the Fc-positive T cells. Pronase digestion experiments showed a graded selective loss of reactivity with the different Fc reagents. No one system was optimal for all of the lymphocyte populations, although aggregated IgG exhibited the broadest spectrum of reactivity. A pronounced effect of temperature was evident on the binding reactions, and native IgG showed strong binding at 4 degrees C, particularly to the Fc receptors on T cells.

Antigen-Antibody Complex↗
PubMed1978

Surface markers of complement receptor lymphocytes.

Normal blood lymphocytes bearing complement receptors (CRL) were divided into two populations, one expressing both CR1 (C4b-C3b receptor) and CR2 (C3d receptor) and a second expressing only CR1. Nearly all of the population that expressed both CR1 and CR2 also bore membrane surface immunoglobulins (Ig) and Ia antigens. The majority of cells that had only CR1 lacked detectable surface Ig. These Ig- CR1+ CR2- cells could be distinguished from the majority of monocytes and immature granulocytes, in that the latter ingested latex particles and expressed CR2 as well as CR1. The Ig- CR1+ cells were further subdivided into an Ia-bearing subpopulation and another that lacked Ia. Among the Ig- Ia- CR1+ cells, one third formed spontaneous rosettes with sheep erythrocytes while all of the remaining CRL were erythrocyte-rosette negative. Essentially all CRL in normal blood had IgG Fc receptors, but a qualitative heterogeneity in the Fc receptors of Ia+ CRL vs. Ia- CRL was observed in their binding of different immune complex systems.

Antigens, Surface↗
PubMed1978

Association of blue rubber bleb nevus syndrome with chronic lymphocytic leukemia and hypernephroma.

A male patient with clinical and pathologic features of blue rubber bleb nevus syndrome is described. Multiple hemangiomata were disseminated throughout the skin and gastrointestinal tract, and typical findings of B cell chronic lymphocytic leukemia and renal cell carcinoma were evident. This case demonstrates a unique instance of associated neoplasia in blue rubber bleb nevus syndrome.

Adenocarcinoma↗
PubMed1977

Parallel synthesis of immunoglobulins and J chain in pokeweed mitogen-stimulated normal cells and in lymphoblastoid cell lines.

The synthesis of intracellular J chains was found to be closely associated with that of intracellular immunoglobulin, regardless of its class, during the process of B-cell differentiation. This parallelism between the synthesis of J chain and immunoglobulin was particularly evident in their coincident appearance in serial observations of pokeweed mitogen (PWM)-stimulated lymphocytes. The intensity of J-chain staining by fluorescent reagents in the stimulated cells synthesizing IgG was similar to that found in cells synthesizing IgA or IgM. Evidence was obtained that the presence of J chain in the IgG-producing cells did not reflect antecedent synthesis of IgA or IgM. T cells stimulated by phytohemagglutinin and PWM failed to show J-chain synthesis. Observations on lymphoid cell lines showed a similar parallelism between intracellular Ig and J-chain synthesis; no relation to surface Ig was found.

B-Lymphocytes↗
PubMed1977

Receptors for IgM on certain human B lymphocytes.

A receptor for IgM was demonstrated on the surface of human B lymphocytes by using a rosette technique with ox erythrocytes coated with rabbit IgM antibody (EAM). Lymphocytes forming rosettes with EAM did not bind sheep red cells, had membrane Ia-like antigens and, in some instances, surface immunoglobulin. The specificity of EAM rosettes was confirmed by inhibition experiments with purified human Ig. IgM but not IgG molecules inhibited the rosette reaction. In addition, inhibition of EAM rosettes with IgM fragments showed that the receptor has affinity for a part of the molecule located in the Fc portion. By analogy with the receptors previously found on certain human T cells, receptors for IgM were not detected on freshly isolated B cells, but were expressed after overnight culture in IgM-free media. Studies on different human lymphoid tissues showed that IgM receptors are expressed on a limited percentage of both circulating and noncirculating B cells. In addition to normal B cells, the malignant B cells of a majority of cases of chronic lymphocytic leukemia expressed the receptors for IgM.

Animals↗
PubMed1976

Studies with B-cell allo- and hetero-antisera: parallel reactivity and special properties.

The expression of B-cell antigens on various cell populations was studied through the use of human alloantisera and with heteroantisera raised to preparations of the alloantigen bearing molecules isolated from B-cell lines. The allo-and hetero-antisera competed with each other in blocking experiments and gave closely parallel results, reacting with normal and leukemic B lymphocytes, monocytes, E-rosette-negative acute lymphatic leukemias, all acute and certain chronic myelogenous leukemias, and a minor population of cells in fetal spleen and liver. These highly immunogenic surface components appeared to comprise the dominant B- cell specific plasma membrane determinants. Neither type of antiserum reacted with any but a minor population of normal or pokeweed-mitogen-transformed T cells, fetal thymic lymphocytes, E-rosette-positive acute lymphatic leukemias, or Sezary-cell leukemia. Through the use of these antisera evidence was obtained that Fc-receptor-bearing Ig-negative lymphocytes were divisible into two groups according to the presence or absence of the B-cell antigens. Both hetero- and allo-antisera blocked binding of immune complexes or antibody-coated ox erythrocytes to Fc receptors on B cells. F(ab')2 fragments of the heteroantibodies strongly inhibited antibody-dependent cell-mediated killing.

Animals↗