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Biomedical subjects

A G Morris

Publications and source records attributed to A G Morris.

At least 91 records · Page 5Linked to original sources
PubMed1985

Interleukin 2 receptor blockade by anti-Tac antibody inhibits IFN-gamma induction.

Anti-Tac antibody, which binds to the interleukin 2 (IL-2) receptor and thus blocks IL-2 binding to and activation of T lymphocytes, was used to investigate the role of IL-2 in interferon-gamma (IFN-gamma) production. Three T-cell mitogens (phytohemagglutinin, concanavalin A, and the pan-T monoclonal antibody OKT3) were used as IFN-gamma inducers. In each case, anti-Tac antibody clearly inhibited IFN-gamma production. This occurred even under conditions where cellular proliferation (as measured by incorporation of [3H]thymidine) was only slightly inhibited. The inhibitory effects of anti-Tac were reversed by the addition of purified IL-2. Therefore, endogenous production of IL-2 and its binding to the IL-2 receptor are needed for maximum IFN-gamma production.

Antibodies, Monoclonal↗
PubMed1985

The effect of interferon treatment of targets on susceptibility to cytotoxic T-lymphocyte killing: augmentation of allogeneic killing and virus-specific killing relative to viral antigen expression.

The effect on CTL lysis of treatment of CTL targets with IFNs has been investigated. Treatment of targets for alloreactive CTL with either IFN-alpha beta or IFN-gamma markedly augmented cytotoxicity. Cold competition experiments implied that CTL recognized the same target structure on both untreated and IFN-treated cells. This augmented lysis is presumably caused by IFN increasing expression of target MHC antigens. In the case of SFV-specific lysis of SFV-infected fibroblasts, IFN-alpha beta or IFN-gamma treatment somewhat reduced CTL lysis, but less so than Ab + C lysis which was abolished at moderate IFN concentrations; in the case of SFV-infected lymphoblastoid cells, CTL lysis remained the same or was slightly increased, whilst Ab + C lysis was reduced at moderate IFN concentrations and abolished at high IFN concentration; in the case of MSV/MLV-infected fibroblasts, CTL lysis was moderately increased whilst Ab + C lysis was decreased. IFN therefore increases virus-specific CTL cytotoxicity relative to viral antigen expression.

Animals↗
PubMed1984

Differences in the expression of the human interferon-gamma gene in fresh lymphocytes and cultured lymphoblasts.

Fresh human peripheral blood mononuclear lymphocytes and lymphoblasts that had been grown for a period in T-cell growth-factor containing medium were stimulated with staphylococcal enterotoxin A plus mezerein to produce interferon-gamma (IFN-gamma). Growing lymphoblasts produced peak levels of IFN-gamma much earlier after induction than fresh lymphocytes. Quantitation of the steady-state levels of IFN-gamma mRNA showed these to differ markedly between the two cell types over a period of time post-induction. In fresh lymphocytes the steady-state levels of IFN-gamma mRNA increased to a peak level over a period of 4 days while in growing lymphoblasts the peak level occurred after 8 hours. These differences in IFN-gamma mRNA production were shown to be not the result of gross alteration of RNA metabolism following blast transformation.

Cells, Cultured↗
PubMed1984

Production of type I (alpha/beta) interferon after virus infection of cloned, alloantigen-sensitized mouse T lymphocytes.

Mouse T lymphocytes sensitized to alloantigens were cloned by limiting dilution in the presence of interleukin 2. Clones were tested for surface markers Thy-1, Lyt-1 and Lyt-2, and for cytotoxic function. Production of interferon (IFN) by clones either (a) stimulated with allogeneic cells; (b) activated with concanavalin A (Con A); or (c) infected with Semliki Forest virus or Newcastle disease virus were assayed. All clones produced IFN upon Con A stimulation and most after virus infection. Analysis of the IFN produced by a single clone, using anti-IFN antisera, showed that while Con A stimulation induced production of type II IFN (IFN-gamma), the IFN produced after virus infection was type I IFN (IFN-alpha/beta).

Animals↗
PubMed1984

Role of the E receptor in interferon-gamma expression: sheep erythrocytes augment interferon-gamma production by human lymphocytes.

The E receptor is found on virtually all human T cells and is defined by its ability to bind to sheep erythrocytes (SRBCs). It was recently shown that a monoclonal antibody (MoAb) binding to the E receptor regulates interferon-gamma (IFN-gamma) production and lymphocyte activation. Here the effects of SRBCs on IFN production is examined since these bind to the E receptor. IFN-gamma production induced by phytohemagglutinin (PHA) in both fresh peripheral blood mononuclear leukocytes ( PBML ) and T-lymphocyte lines was augmented by 5- to 10-fold when cultured with SRBCs. The SRBCs increased IFN by interacting with the E receptor since its augmenting effect was blocked by the E-receptor MoAb 9.6. The augmenting effect of SRBCs was independent of blastogenic events since DNA synthesis was not similarly augmented by SRBCs and because IFN-gamma production was only increased after blastogenesis had occurred (in already differentiated lymphoblasts or in PBML 2-3 days after induction). Since it was found that only a short pulse of SRBCs was required for their action, this suggests that the studies employing SRBC rosetting as a fractionation technique for investigating the cell source of IFN-gamma should be viewed with caution.

Animals↗
PubMed1984

Gamma interferon production and cytotoxicity of spleen cells from mice infected with Semliki Forest virus.

Interferon (IFN) production by spleen cells from normal mice, mice acutely infected with Semliki Forest virus (SFV) or mice immune to SFV was measured after stimulation in vitro with either infectious or inactivated SFV. All three classes of spleen cells made IFN-alpha beta in response to infectious SFV. Spleen cells taken from mice late, but not early, after infection, or from immune mice, made IFN-gamma in response to inactivated SFV. Amounts of INF-gamma and IFN-alpha beta were similar. Normal spleen cells made no IFN (of any type) in response to inactivated SFV. The cell type producing IFN-alpha beta appeared to be the macrophage, whilst both T-lymphocytes and macrophages were necessary for IFN-gamma production. During the acute infection, the ability of spleen cells to lyse both virus-infected and uninfected target cells arose earlier than the ability to produce IFN-gamma. However, cytotoxicity towards uninfected cells fell to near background levels by day 7, whilst cytotoxicity towards infected targets remained high at that time, when IFN-gamma production was at its peak. IFN-gamma production is therefore temporally associated with cytotoxicity specifically directed against virus-infected targets, and the ability to produce IFN-gamma is a late response to SFV infection.

Animals↗
PubMed1984

Gamma-interferon induction in human lymphoblasts compared with fresh mononuclear leucocytes: earlier synthesis, rapid shut-off and enhancement of yields by metabolic inhibitors.

The mechanisms of gamma-interferon (IFN-gamma) induction in fresh human peripheral blood mononuclear leucocytes (PBML) and proliferating lymphoblasts were compared. Cotreatment with mitogen (Staphylococcal enterotoxin A) and tumour promoter (mezerein) was used to induce maximum IFN-gamma production and thus to study the induction process under optimum conditions. Total IFN yields were about the same from both cell types. Proliferating lymphocytes produced IFN much earlier and more transiently than fresh PBML. Experiments with actinomycin D indicated that de novo synthesis of RNA was required for IFN-gamma production in both PBML and lymphoblasts, but that for maximal IFN-gamma production, lymphoblasts required RNA synthesis for a shorter period (1 hr) after induction than did fresh PBML (greater than 15 hr). Appropriate schedules of treatment with metabolic inhibitors actually increased IFN production in lymphoblasts. This 'superinduction' could not be demonstrated for fresh PBML, implying differences in the turn-off of IFN-gamma production in these two cell types. Taken together, these results indicate that IFN-gamma expression is regulated differently in quiescent and activated lymphocytes.

Dactinomycin↗
PubMed1983

Production of interferons during experimental African trypanosomiasis.

African trypanosomiasis is associated with profound changes in the function of the immune system. In this study we find that alpha/beta and gamma interferon (IFN) are released into the serum of mice infected with Trypanosoma brucei. The parasite-induced rise in serum IFNs is associated with a detectable parasitaemia, but the serum IFN peak precedes the peak parasitaemia in some cases. Unlike other protozoan interferon inducers, no parasite-dependent IFN production was observed in the pre-patent period of infection; while the most virulent clone induced very high IFN levels, no clear difference in stimulation was noted in the first waves of semi-acute and chronic T. brucei clones. However, subsequent IFN augmentation more closely reflected the host parasite load and virulence of infection. The nature of the stimulatory parasite component is as yet unknown, and the parasite surface glycoprotein had no effect on serum IFN. Injection of large quantities of lethally irradiated, but intact organisms did not stimulate IFN production; however this treatment significantly impaired antibody responses to the heterologous antigen SRBC. This suggests that the more severe effects of an actual trypanosome infection are required for induction of IFN synthesis, and that the presence of measurable serum IFN is not a prerequisite for parasite-induced suppression of host antibody responses.

Animals↗
PubMed1982

Lawrence Herbert Wells and the history of anatomical illustration.

The pre-Vesalian history of anatomical illustration, including its ancient Greek and Roman periods, is surveyed. While dissection was abandoned in Alexandria under the Romans, it was revived in Italy during the Renaissance, and the invention of printing prompted the avalanche of documents which has cascaded ever since. The considerable contribution of the late Professor Lawrence H. Wells to the history of anatomical illustration is emphasized and his interest in 'fugitive sheets', popular in the 15th and 16th centuries, is indicated.

Anatomy↗
PubMed1982

Spontaneous production of gamma interferon and induced production of beta interferon by human T-lymphoblastoid cell lines.

Two human T-lymphoblastoid cell lines, CCRF/CEM and Molt 4, produced beta interferon (IFN-beta) upon infection with Sendai virus. Molt 4, but not CCRF/CEM, spontaneously produced up to 300 U of IFN-gamma per ml, apparently not contaminated with IFN-alpha or -beta. Phytohemagglutinin, a T-cell mitogen, did not stimulate IFN production in these lines. A third T-lymphoblastoid line, CCRF/HSB2, produced no IFN either spontaneously or after infection with Sendai virus or treatment with phytohemagglutinin. The Molt 4 cells contained an mRNA which could be translated by oocytes to give IFN-gamma. Molt 4 cells therefore provide a convenient source of human IFN-gamma and its mRNA for experimental purposes.

Bromodeoxyuridine↗
PubMed1981

Neoplastic transformation of mouse fibroblasts by murine sarcoma virus: a multi-step process.

Infection of cultures of three different normal rodent cell lines with murine sarcoma virus (MSV) resulted in very rapid loss of contact inhibition of growth and morphological transformation. In the case of two of these lines, anchorage dependence of growth was also rapidly lost but with the 3rd, C3H10T1/2 C1.8, an established line of mouse embryo fibroblasts, there was a delay of many cell generations before the cells became anchorage independent. This was despite 100% successful infection, as assessed by focus assays of the infected cells. The acquisition of anchorage independence was correlated with a substantial increase in tumorigenicity. A number of MSV-infected clones, isolated at random from C3H10T1/2 C1.8 cultures immediately after infection with MSV, also showed a progressive increase in anchorage independence and tumorigenicity, indicating that the progressive transformation of the uncloned cells could not be entirely due to selection of rare anchorage-independent, tumorigenic clones. It was concluded that neoplastic transformation of C3H10T1/2 C1.8 cells by MSV is a multi-step process.

Animals↗
PubMed1981

Partial reversion of the transformed phenotype of murine sarcoma virus-transformed cells in the presence of interferon: a possible mechanism for the anti-tumour effect of interferon.

The effect of interferon (IFN) on a series of cellular properties which characterize the transformed state was studied, using normal mouse fibroblasts (both established lines and embryo cells) and cloned derivatives transformed by murine sarcoma virus. It was found that the transformed cells behaved in a more normal fashion in the presence of IFN. This was indicated by reduction in saturation density, decreased DNA synthesis in crowded cultures, decreased formation of foci on monolayers of normal cells, and decreased growth in soft agar. These effects were not due to generalized inhibition of cell growth, since IFN had little effect on the growth and cloning efficiency of the cells used. In the presence of IFN, cellular morphology also appeared more normal. These results suggest that growth control of transformed cells may be at lease partly restored by IFN, an effect which could in part account for the anti-tumour effect of IFN

Animals↗
PubMed1981

Saccades of hyperactive and normal boys during ocular pursuit.

Eye movements of hyperactive and normal boys were compared on a visual pursuit task in three experiments. In the first series of tests, irregular pursuit occurred more often in hyperactive than in normal boys. Hyperactive boys made more saccadic movements, their average saccades were larger, and they looked away from the pursuit path more frequently than the normal boys. In a second series of tests three years later, the differences between normal and hyperactive boys still existed. In a third set of experiments the effects of an attention task, different stimulus velocities and stimulant medication were studied in another group of control and hyperactive boys. With or without the attention task, hyperactive boys not receiving stimulant medication made more saccades than normal boys. Differences were greatest at lower target velocities and decreased at higher stimulus velocities. Differences between hyperactive and normal boys disappeared when the former received both stimulant medication and the attention task. The findings were the same in the two groups of hyperactive boys: they had more saccades superimposed on ocular pursuit than did normal boys. Differences between the groups may be related to their relative ability to attend to the target. The differences are of a magnitude that might make them useful as an adjunct for diagnosis of hyperactivity or for evaluating the effects of treatment.

Adaptation, Physiological↗
PubMed1980

Interferon inhibits transformation by murine sarcoma viruses before integration of provirus.

Neoplastic transformation by C-type retroviruses requires synthesis of a DNA copy (the provirus) of the RNA genome and its integration into the host cell DNA. We have previously shown that interferon (IFN) can stably prevent transformation of murine fibroblasts by the Kirsten strain of murine sarcoma virus (KiMSV), a murine leukaemia virus (MLV). A series of cell clones (IFN clones), isolated in the presence of IFN (10(4) U ml-1) from cultures of NIH-3T3 cells which had been treated with IFN, and then infected with KiMSV (KiMLV) in conditions where every cell was infected, were shown to be phenotypically untransformed. These untransformed cells did not produce virus or contain rescuable KiMSV. However, cells isolated using an identical procedure, but in the absence of IFN, were uniformly transformed and all produced KiMSV (KiMLV) or contained rescuable KiMSV. It was concluded that IFN either prevents synthesis or integration of the provirus, or else that in the presence of IFN the provirus is integrated such that it is not expressed. We now show that five representative clones contain no detectable KiMSV proviral DNA, and also that the initial stages of infection by KiMSV (KiMLV) are inhibited by IFN treatment. IFN seems to act before integration, preventing either the synthesis or the integration of proviral DNA.

Animals↗
PubMed1979

An interferon-sensitive early step in the establishment of infection of murine cells by murine sarcoma/leukaemia virus.

NIH 3T3 mouse cells were infected at very high multiplicity with murine sarcoma/leukaemia virus (MSV/MLV) and then cloned. All of the 48 clones obtained were morphologically transformed, all but one showed anchorage-independence of growth, typical of MSV-transformed NIH 3T3 cells and most (91%) produced MSV/MLV. When cells which had been pre-treated with 10(4) units/ml of purified interferon (IF) were infected under the same conditions and then cloned in the presence of the same amount of IF, only 6 of a total of 63 clones were morphologically transformed. All but these 6 showed a degree of anchorage-independence typical of the uninfected parental cells and very few (2.4%) produced virus. Furthermore, the MSV genome could not be rescued in any of the 23 clones tested and only 1 out of 10 clones produced tumours. The properties of these clones remained stable over a period of 10 to 20 passages in the absence of interferon. We conclude that interferon can irreversibly block an early step in the MSV/MLV infectious process.

Animals↗