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Biomedical subjects

R Palacios

Publications and source records attributed to R Palacios.

At least 181 records · Page 10Linked to original sources
PubMed1981

Cimetidine abrogates suppressor T cell function in vitro.

Cimetidine increased the [3H] thymidine incorporation of normal human mononuclear cells in culture both when unstimulated or when under the stimulus of phytohemagglutinin or pokeweed mitogen (PWM). It also increased their supernatant immunoglobulin production under PWM stimulus. These effects were higher when the cells were preincubated with cimetidine than when it was added simultaneously. To determine if this effect of cimetidine reflects an abrogation of suppression we studied concanavalin-A-induced suppressor function of normal mononuclear cells using both [3H] thymidine incorporation and immunoglobulin synthesis as indicator systems and found that preincubation with cimetidine caused significant decrease in suppressor cell function in both systems.

Cimetidine↗
PubMed1981

Cyclosporin A abrogates proliferation of T cells and generation of suppressor and cytotoxic T-cell function induced by Epstein-Barr virus.

Cyclosporin A (CYA) promotes the outgrowth in vitro of Epstein-Barr-virus(EBV)-infected cells of immune donors. In the present study, the effects of CYA on the T-cell responses developed to an in-vitro EBV infection were studied. Cyclosporin A, by acting on the responder cells and not on stimulator cells, strongly inhibited the proliferation of T cells normally induced by EBV-infected autologous cells. Moreover, T cells from cultures not exposed to CYA exerted suppression on both alloantigen-induced DNA synthesis and PWM-stimulated immunoglobulin producton of autologous peripheral blood mononuclear cells. In contrast, T cells from cultures treated with CYA exhibited significantly less or no suppressor activity as determined in both indicator system. Finally, CYA abrogated the generation of cytotoxic T cells against EBV-infected autologous cells, whereas non-CYA -treated T cells killed the virus-transformed target cells. Both suppressor and cytotoxic T-cell functions are known to play an essential role in the control of EBV infection by limiting the continuous growth of the virus-infected cells. These results, therefore, stongly suggest that cyclosporin A promotes the outgrowth of EBV-infected cells by abrogating the T-cell responses to the Epstein-Barr virus.

Animals↗
PubMed1981

Human post-thymic precursor cells in health and disease. III. Role of the autologous rosette-forming T cells in the generation of spontaneous killer cells in the autologous mixed lymphocyte reaction.

Adult peripheral blood T lymphocytes activated in autologous mixed lymphocyte reactions (AMLR) exerted cytotoxicity on both phytohaemagglutinin-stimulated cells and Epstein-Barr virus-transformed cells. When autologous rosette-forming T cells were removed from total T lymphocytes, there was no generation of cytotoxicity. Re-addition of autologous rosette-forming T cells (Tar cells) to a population of T cells depleted of Tar cells restored the cytotoxic activity. Treatment of Tar cells with mitomycin C before their activation in AMLR caused loss of their capacity to give rise to killer cells. Furthermore, resting Tar cells did not show any cytotoxic activity as determined in the two different types of target cells used. Since Tar cells are able to differentiate into T gamma cells and since T gamma cells possess spontaneous cytotoxic activity, it is likely that Tar cells participate in the generation of spontaneous killer cells in AMLR as precursors of cytotoxic effector cells.

Cell Separation↗
PubMed1981

HLA-DR antigens render interleukin-2-producer T lymphocytes sensitive to interleukin-1.

Monoclonal anti-HLA-DR antibodies inhibited the production of interleukin-2 (IL-2) when added from the initiation of autologous (AMLR) and allogeneic (MLR) mixed lymphocyte reactions, but not 60 h later. The inhibitory activity of the anti-DR sera became apparent 8 h after initiation of the cultures and was maintained throughout the culture period. Interleukin-1 (IL-1) added to cultures carried out in the absence of the anti-DR antibodies significantly enhanced the production of IL-2, whereas addition of IL-1 to anti-DR-treated AMLR and MLR cultures did not restore or increase the synthesis of IL-2. However, when the anti-DR antibodies were added to IL-1-supplemented AMLR and MLR cultures 60 h or more after initiation of the reactions, the antiserum no longer inhibited the capacity of IL-1 to promote the synthesis of IL-2 or the production of IL-2. Finally, resting T cells were unresponsive to IL-1 and did not produce IL-2. It thus seemed that the anit-DR antibodies inhibited production of IL-2 in AMLR and MLR by rendering the IL-2 producer T cells unresponsive to IL-1. Cyclosporin-A, a drug that abrogates activation of T cells by blocking their receptors for HLA-DR antigens, also rendered IL-2 producer T cells unresponsive to IL-1 and abrogated the production of IL-2 in AMLR and MLR. Since resting T cells cells do not respond to IL-1 or produce IL-2, it is concluded that HLA-DR antigens of the stimulator cells participate in the production of IL-2 in AMLR and MLR by enabling the IL-2 producer T lymphocytes to respond to IL-1. Interleukin-1 promotes the production of IL-2 by IL-1-sensitive T cells. Once the IL-2-producer T cells become sensitive to IL-1, there is no further requirement for HLA-DR antigens.

Adult↗
PubMed1981

Human postthymic precursor cells in health and disease. VII. Immunoregulatory circuits of the peripheral blood mononuclear cells from patients with progressive systemic sclerosis.

The study of T cell subpopulations and their immunoregulatory circuits in 9 patients with progressive systemic sclerosis (PSS) and 9 age/sex matched controls showed: 1. Normal postthymic precursor autologous rosette-forming T cells (Tar cells). 2. Normal T cells with receptors for the Fc portion of IgG(Ty). 3. Decreased T cells with receptor for Fc portion of IgM(Tmu). 4. Normal function of postthymic precursors. 5. Normal Concanavalin-A-induced and spontaneously-expanded suppressor cell functions. 6. Abnormally increased T helper cell function. These findings suggest that the primary immunoregulatory aberration in PSS is at the level of Tmu cells and their helper function. Relationship between this T cell disturbance and fibroblast function may explain the pathogenesis of PSS.

B-Lymphocytes↗
PubMed1981

Human post-thymic precursor cells in health and disease. I. Characterization of the autologous rosette-forming T cells as post-thymic precursors.

Human autologous-rosette-forming T cells (Tar cells) have many of the characteristics of post-thymic precursor cells. Thus, they bind to sheep erythrocytes but have neither receptors for the Fc portion of IgG nor for that of IgM. They include a subpopulation that binds peanut agglutinin which suggests that they are immature and, as opposed to T cells with either receptors for the FC portion of IgM (T mu) or of IgG (T gamma), Tar cells adhere to nylon wool, another possible indicator of immaturity, as is their extreme sensitivity to hydrocortisone both in vitro and in vivo. There are more Tar cells in cord blood than in the peripheral blood of young adults and there are more Tar cells in the peripheral blood of young adults than in the peripheral blood of elderly subjects. By co-culturing T mu and B cells, or T mu, or Tar and B cells in the presence of pokeweek mitogen (PWM) we were able to determine that these cells cause feedback inhibition, a function considered characteristic of post-thymic precursors. In co-cultures in which we placed mononuclear cells (MNC) or MNC plus Tar cells, or MNC depleted of Tar cells or MNC depleted of Tar cells plus Tar cells stimulated with PWM, we determined that Tar cells play a role in the generation of suppression thereby confirming that human Tar cells are precursor cells. We also found that Tar cells proliferated and generated T gamma and T mu cells both spontaneously and in greater numbers, under the effect of serum thymic factor.

Adult↗
PubMed1981

Human postthymic precursor cells in health and disease. II. Their loss and dysfunction in systemic lupus erythematosus and their partial correction with serum thymic factor.

We have recently described that human autologous rosette-forming (Tar) cells have the characteristics of postthymic precursor cells. Herein we report that we found circulating Tar cells significantly diminished in 32 patients with untreated systemic lupus erythematosus (SLE) as compared to 32 age/sex matched controls. Pretreatment of peripheral blood mononuclear cells (MNC) from SLE patients with serum from young normal adults or wtih serum thymic factors (FTS) increased their percentages of Tar cells significantly but reached near normal values in only 3 patients with inactive disease. Patients and normal subjects had similar percentages of Tar cells binding peanut-agglutinin. Characteristic functions of postthymic precursor cells are feedback inhibition and generation of suppressor cells which we studied in systems where we depleted or added Tar cells to Tmu and B cells, or MNC, respectively, using as indicators the production of immunoglobulins measured in culture supernatants or 3H-thymidine incorporation. We found both functions diminished in SLE patients despite using the presence of a qualitative as well as quantitative defect. In two SLE patients studied both of these functions corrected partially when their Tar cells were pretreated with FTS. In 20 SLE patients we studied Tgamma and Tmu cells as well as Concanavalin-A-induced, spontaneously-expanded suppression and found Concanavalin-A-induced, spontaneously-expanded suppressor function and Tgamma cells diminished. However only the reduction of Tgamma and of spontaneously-expanded suppressor function were found to relate to disease activity. On the other hand, Tmu cells were found to be similar in numbers in SLE patients and normal controls.

Adult↗
PubMed1981

Human post-thymic precursor cells in health and disease. IX. Immunoregulatory T cell circuits in peripheral blood of patients with rheumatoid arthritis.

We studied T cell subpopulations and their immunoregulatory circuits in the peripheral blood of 16 patients with rheumatoid arthritis (RA) who were receiving no medications that might interfere with the results. We found normal T cells with receptors for the Fc portion of IgG or IgM as well as autologous rosette-forming T cells (Tar cells), a subpopulation of T cells we have found to have the properties of human post-thymic precursors. We also found that peripheral blood cells of RA patients have normal concanavalin A-induced or spontaneously-expanded suppressor cell functions. Also normal were the characteristic functions of the Tar cells; feedback inhibition and the generation of suppression. The normal state of these T cell subpopulations and immunoregulatory circuits in the peripheral blood of patients with RA contrasts with their various abnormalities in other connective tissue diseases. This may either mean that the immunoregulatory aberration in RA involves primarily B cells, or, if it involves T cells, that it does so primarily in the synovial membrane.

Arthritis, Rheumatoid↗
PubMed1980

Heterogeneity of glutamine synthetase polypeptides in Neurospora crassa.

Purified preparations of Neurospora crassa glutamine synthetase contain two nonidentical polypeptides that can be separated by acrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and 7 M urea. These polypeptides are synthesized both in vivo and in a heterologous cell-free protein-synthesizing system. The data presented indicate that both polypeptides contain an active site for glutamine synthetase activity and suggest that there is not a precursor-product relationship between them.

Glutamate-Ammonia Ligase↗
PubMed1980

Autologous rosette-forming T cells as the responding cells in human autologous mixed-lymphocyte reaction.

Autologous rosette-forming cells (Tar cells) have surface and functional characteristics of post-thymic precursors and among these characteristics there are some that have been identified in the responsive cell of the autologous mixed-lymphocyte reaction (AMLR). We therefore did AMLR with circulating mononuclear cells from normal subjects using as responding cells either total T cells, T cells depleted of Tar cells, or purified Tar cells. The response of Tar cells in AMLR was significantly greater than that of total T cells and these responded significantly more than Tar-depleted T cells. Conversely, Tar cells responded less than total T cells or T cells depleted of Tar cells in allogeneic mixed-lymphocyte reactions. Increasing numbers of Tar cells gave significantly greater AMLR responses both alone and when added to diminishing proportions of Tar-depleted T cells to keep the number of T cells constant in the system. Tar cells are the responding cells in AMLR but not in allogeneic mixed-lymphocyte reactions.

Humans↗
PubMed1979

Glutamine metabolism in nitrogen-starved conidia of Neurospora crassa.

During nitrogen deprivation, de novo synthesis of glutamine synthetase was induced in non-growing conidia of Neurospora crassa. When ammonia or glutamine was added to conidia which had been deprived of nitrogen, glutamine and arginine accumulated at a higher rate than in condia not deprived of nitrogen. The degradation of exogenous glutamine to glutamate is apparently a necessary step in the accumulation of glutamine and arginine within the conidia. In non-growing conidia, a cycle probably operates in which glutamine is degraded and resynthesized. The advantages of such a cycle would be that the carbon and nitrogen could be used to synthesize amino acids in general, as well as for the synthesis and accumulation of arginine and/or glutamine in particular.

Arginine↗
PubMed1979

Immunochemical characterization of glutamine synthetase from Neurospora crassa glutamine auxotrophs.

Glutamine synthetase derived from two Neurospora crassa glutamine auxotrophs was characterized. Previous genetic studies indicated that the mutations responsible for the glutamine auxotrophy are allelic and map in chromosome V. When measured in crude extracts, both mutant strains had lower glutamine synthetase specific activity than that found in the wild-type strain. The enzyme from both auxotrophs and the wild-type strain was partially purified from cultures grown on glutamine as the sole nitrogen source, and immunochemical studies were performed in crude extracts and purified fractions. Quantitative rocket immunoelectrophoresis indicated that the activity per enzyme molecule is lower in the mutants than in the wild-type strain; immunoelectrophoresis and immunochemical titration of enzyme activity demonstrated structural differences between the enzymes from both auxotrophs. On the other hand, the monomer of glutamine synthetase of both mutants was found to be of a molecular weight similar to that of the wild-type strain. These data indicate that the mutations are located in the structural gene of N. crassa glutamine synthetase.

Genes↗
PubMed1978

Nitrogen regulation of glutamine synthetase in Neurospora crassa.

A higher activity of glutamine synthetase (EC 6.3.1.2) was found in Neurospora crassa when NH4+ was limiting as nitrogen source than when glutamate was limiting. When glutamate, glutamine or NH4+ were in excess, a lower activity was found. Immunological titration and sucrose gradient sedimentation of the enzyme established that under all these conditions enzyme activity corresponded to enzyme concentration and that the octamer was the predominant oligomeric form. When N. crassa was shifted from nitrogen-limiting substrates to excess product as nitrogen source, the concentration of glutamine synthetase was adjusted with kinetics that closely followed dilution by growth. When grown on limiting amounts of glutamate, a lower oligomer was present in addition to the octameric form of the enzyme. When the culture was shifted to excess NH4+, glutamine accululated at a high rate; nevertheless, there was only a slow decrease in enzyme activity and no modification of the oligomeric pattern.

Culture Media↗
PubMed1978

Genetics and physiology of Neurospora crassa glutamine auxotrophs.

This work reports on the isolation and characterization of two glutamine auxotrophs in Neurospora crassa. The mutations responsible for the glutamine-requiring phenotype were very closely linked, and one of them proved to be recessive to wild type. The mutations impaired the conversion of glutamic acid to glutamine and resulted in changes of both the activity and oligomeric structure of the enzyme glutamine synthetase.

Ammonia↗
PubMed1978

Nitrogen source regulates glutamine synthetase mRNA levels in Neurospora crassa.

Neurospora crassa glutamine synthetase mRNA was measured by its capacity to direct the synthesis of the specific protein in a cell-free system derived from rabbit reticulocytes. N. crassa cultures grown on glutamate as the sole nitrogen source had higher mRNA activities than did those grown on glutamine. The differences were about 10-fold when polysomal RNA was used for translation and about 5-fold when either total cellular RNA or polyadenylic acid-enriched cellular RNA was used. These data indicate that in exponentially growing N. crassa, the nitrogen source regulates glutamine synthetase by adjusting specific mRNA levels.

Cell-Free System↗