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Allotype suppression in the chicken. IV. Deletion of B cells and lack of suppressor cells during chronic suppression.

Embryonally induced allotype suppression in M-1,G-1 heterozygous chickens was stable for at least 18 months after hatching. Suppression was established rapidly since injection of antigen only 4 days after anti-IgM-1 antiserum failed to abrogate its effect. Injected chickens had undetectable serum levels (i.e. less than 40 micrograms/ml) of the suppressed IgM-1 and low (0.3-0.6 mg/ml) levels of the linked IgG-1 allotype. This correlated with a complete depletion of cells bearing the relevant IgM-1 allotypes and a compensatory increase in the alternative nonsuppressed IgM-1 allotype-bearing cells in the spleen, peripheral blood and bursa. Cell transfer studies suggested that suppression could not be attributed to allotype-specific suppressor cells.

Animals↗

Individual differences in thought suppression. The White Bear Suppression Inventory: factor structure, reliability, validity and correlates.

The White Bear Suppression Inventory [WBSI; Wegner, D.M. & Zanakos, S. (1994), Journal of Personality, 62, 615-640] is a self-report questionnaire measuring people's general tendency to suppress unwanted negative thoughts. The current article describes two studies investigating the reliability, factor structure, validity, and correlates of the WBSI. Study 1 (n = 172) showed that the WBSI is a reliable instrument in terms of internal consistency and test-retest stability. Factor analyses of the WBSI revealed a 1-factor solution. Furthermore, the WBSI was found to correlate positively with measures of emotional vulnerability and psychopathological symptoms. In Study 2 (n = 40), the relationship between WBSI and levels of intrusive thinking was examined in more detail, using a thought suppression task. In general, results of this thought suppression experiment provided evidence for the validity of the WBSI. That is, subjects with high WBSI scores exhibited higher frequencies of unwanted intrusive thoughts than subjects with low WBSI scores.

Adolescent↗

Selective suppression of allotype expression induced in vitro: maintenance of suppression following adoptive transfer.

The question of the ultimate fate of lymphocytes subjected to treatment with anti-allotype antibody (Ab) has been investigated by means of an adoptive transfer system that uses noninbred rabbits matched for major histocompatibility antigens and mismatched for allotype. Suppression of b4 immunoglobulin (Ig) production was induced by incubating lymphocytes from b4b5 rabbits with anti-b4 in culture. Transfer of b4-suppressed cells to newborn recipients of allotype b6b6 resulted in stable chimerism of mixed donor-recipient allotypes, in which b4 Ig production remained suppressed. In recipients of non-Ab-treated cells, b4 Ig production predominated over b5, as had been the case in the intact donor. No evidence for stimulation of b4 Ig synthesis was seen, even when lymphocytes and serum from 1-week-old recipients were examined. When lymphoid cells of antigen-primed b4b5 donors were treated with anti-b4 in vitro and transferred, Ab production of the b4 type was specifically suppressed, with compensatory over-production by Ab-forming cells of the b5 type. The results reported here indicate that although anti-allotype Ab is not directly cytotoxic, a significant proportion of the b4-committed cells were irreversibly inactivated as a result of Ab pulse treatment.

Animals↗

Features of KLH-induced suppression in vivo: characterization of two pathways of suppression.

Keyhole limpet hemocyanin (KLH) given at high dose (4 mg ip) in mice induced a state of unresponsiveness related to the activation of suppressor T cells. An early pathway of suppression is observed within the first 24 hr following KLH injection and is characterized by its cyclophosphamide (CPM) sensitivity and by the specificity of its effector phase, at the level of KLH helper T cells. A late pathway of suppression occurs at Day 3 following KLH injection and is characterized by its CPM resistance and the nonspecificity of its effector phase acting at the B-cell level. Indeed the anti-FLu antibody response to FLu Ovalbumin or thymus-independent antigen FLu LPS were found altered when these antigens were given with TNP KLH. These two pathways of suppression were found to last 8 months. These results suggest that KLH can trigger in an independent manner two pathways of suppression characterized by different CPM sensitivity and different target cells.

Animals↗

Plasma lipoproteins can suppress accessory cell function and consequently suppress lymphocyte activation.

The low density classes of plasma lipoproteins (d less than or equal to 1.063 g/ml) suppress mitogenic activation and proliferation of peripheral blood T lymphocytes. Here we demonstrate that lipoprotein suppression can be directed against the accessory cells (greater than 85% monocytes) required for optimal activation of lymphocytes by polyclonal mitogens. Preincubation of accessory cells for 24 h with very low (VLDL) and low (LDL) density lipoproteins suppressed their ability to enhance lymphocyte activation, whereas preincubation of T lymphocytes with lipoproteins did not alter their responsiveness to mitogens. The phenotypic distribution of the accessory cell population was not specifically altered by the lipoproteins, nor did loss of viability account for the suppressive effect of the lipoproteins. Furthermore, the lipoprotein-preincubated accessory cells did not secrete stable inhibitory substances, nor was their ability to produce interleukin 1 diminished. The results of mixing experiments indicate that VLDL-incubated accessory cells had not differentiated into suppressor cells. The lipoprotein-incubated accessory cells appeared to induce the interleukin 2-responsive state in the mitogen-activated lymphocytes, but could not deliver a signal or signals required for the further progression of the activated lymphocytes through the cell cycle. These important findings define at least two types of accessory cell function in the in vitro activation of T lymphocytes.

Cell Survival↗

Suppression of mouse killing by lateral hypothalamic infusion of atropine sulfate in the rat: a general behavioral suppression.

Male hooded rats which had been induced to kill mice by food deprivation had intracranial cannulas implanted into the lateral hypothalamus. Injections of 3 microliter to each side of the brain blocked mouse killing in 12 out of 15 animals when the injected substance was the general blocking agent lidocaine. Atropine sulfate produced a significant suppression of mouse killing at a dose of 15 microgram to each hemisphere but not with doses of 1.8 or 6.0 microgram. The 15 microgram but not the 1.8 microgram dose also suppressed food intake. It is argued that the cholinergic antagonist atropine sulfate only suppresses mouse killing at high doses which produce a general suppression of behavior.

Aggression↗

Suppressive characteristics of the cultured umbilical cord blood lymphocytes: enhanced suppression of non specific MLR by short term cultured peripheral blood and rosetted lymphocytes.

We have used the mixed leukocyte reaction assay (MLR) to compare the non-specific suppressor activity of fresh and short-term cultured peripheral blood rosetted lymphocytes from human umbilical cord blood. To a one way MLR between adult responders and irradiated adult stimulator cells, we added adult or cord blood mononuclear cells. Cord-blood derived mononuclear cells were more potent suppressors of the MLR than the adult peripheral blood mononuclear cells. When the fresh cord blood T cell fraction was separated from non-T cells by rosetting, the frequency and capacity of suppression fell, suggesting a role of non-T cells in this phenomenon. However, short-term culture (up to nine days) of cord blood derived T cells in the absence of mitogen resulted in a significant increase in their suppressive characteristics. Maternal cells were not used in any of these assays and the suppression was non specific. There was no HLA restriction to the response. The cord blood lymphocytes responded poorly to alloantigen when compared to the adult lymphocytes. In addition, there was a correlation between the allogeneic proliferative response and the suppressive capacity of the cord blood cells. Such a correlation was not found with the adult peripheral blood lymphocytes.

Adult↗

Suppression of F-VEP during isoflurane-induced EEG suppression.

We recorded visual evoked potentials (VEPs) to flash stimuli in moderately deep anaesthesia when EEG showed burst suppression pattern. Flash VEPs could consistently be recorded in all 8 test subjects during bursts but not during suppressions. We conclude that during isoflurane-induced EEG suppression VEPs to flash stimuli are also suppressed. This effect should be taken into account in evoked potential testing during anaesthesia.

Adult↗

Two-tone suppression in inner hair cell responses: correlates of rate suppression in the auditory nerve.

Inner hair cell (IHC) recordings were made from second turn of the guinea pig cochlea where characteristic frequencies are approximately 4000 Hz. In order to compare IHC responses with rate suppression measured in the auditory nerve, suppressors were introduced that produced little or no response in the hair cell. The effects of a variable-frequency suppressor on a constant-frequency probe, placed near characteristic frequency, were also investigated since this paradigm is commonly used in single unit experiments. Resulting magnitude changes were measured in the fundamental component of the ac receptor potential and/or in the total dc produced in the region of temporal overlap between the two stimulus inputs. This latter component is especially important when considering how changes in IHC responses relate to decreases in discharge rate in single auditory nerve fibers. Since the ac receptor potential is filtered by the hair cell's basolateral membrane, the dc component probably controls transmitter release at the characteristic frequency of these second-turn IHCs. Based on results from these and previous experiments, a proposal is advanced to explain the evolution of two-tone suppression in the peripheral auditory system. The paper also discusses the use of excitatory versus non-excitatory suppressors and includes a description of two-tone suppression areas at the mechanical, IHC and single unit levels. The explanation of low-side suppression areas is of special interest since hitherto they have been difficult to model (Kim, 1985).

Acoustic Stimulation↗

Estrogen-induced suppression of collagen arthritis. III. Adult thymectomy does not affect the course of arthritis or the estrogen-mediated suppression of T-cell immunity.

Type II collagen-induced arthritis is dependent on the activation of T-helper cells and is modulated by female sex hormones. It is shown that treatment of castrated female DBA/1 mice with beta-estradiol decreases the incidence (32% vs 88%) as well as the severity of the disease. The estrogen-induced suppression of both the development of collagen arthritis and T-cell immunity were not dependent on the thymus. Thus, estrogen treatment of thymectomized and castrated female mice suppressed the incidence (21% versus 100% in controls) and severity of arthritis. Similarly, estrogen treatment of thymectomized and castrated female mice suppressed both antigen-specific delayed-type hypersensitivity and T-cell proliferative responses. These data suggest that the estrogen-mediated suppression of arthritis and T-cell immunity is not dependent on the presence of an intact thymus.

Animals↗

Agonists that suppress M-current elicit phosphoinositide turnover and Ca2+ transients, but these events do not explain M-current suppression.

The hypothesis that acetylcholine, substance P, and LHRH suppress M-current by activating phospholipase C was tested. Each agonist caused turnover of phosphoinositide, as measured by release of inositol phosphates, and a modest transient rise in intracellular free Ca2+ ([ Ca2+]i), as determined with fura-2. Active phorbol esters depressed M-current only 50% and did not prevent further suppression by LHRH. M-current, its control by agonists, and its depression by phorbol esters were not affected by adding inositol trisphosphate or Ca2+ buffers with high or low Ca2+ to the whole-cell, voltage-clamp pipette. We conclude that phospholipase C activation does occur but does not mediate the suppression of M-current by agonists. Caffeine produced large [Ca2+]i transients and acted as an agonist to suppress M-current.

Acetylcholine↗

Combination of suppressed and non-suppressed ion chromatography with atmospheric pressure ionization mass spectrometry for the determination of anions.

Non-suppressed and suppressed ion chromatography in combination with atmospheric pressure ionization mass spectrometry are compared with special respect to sensitivity for the analysis of low-molecular-mass anions. Iodate, bromate, bromide, sulfate, thiosulfate and bromide could be separated by non-suppressed ion chromatography using a low-capacity anion-exchange column and ammonium citrate as mobile phase. Absolute detection limits between 0.4 and 0.7 ng could be achieved; employing a column requiring a flow-rate of 1 ml/min for optimum performance, splitting was necessary so that only 120 microliters/min entered the interface of the mass spectrometer resulting in detection limits between 0.03 and 0.06 mg/l. The same stationary phase (packed into a narrow-bore column which allowed operation without splitting) was suitable for the separation of oxyhalides in the suppressed mode with detection limits of 0.5 microgram/l (50 pg) with sodium carbonate as eluent. The method was applied to the analysis of drinking water for oxyhalides. The sample pretreatment for the removal of matrix anions (sulfate, chloride and hydrogencarbonate) is described.

Anions↗

Fosfomycin (FOM: 1 R-2S-epoxypropylphosphonic acid) suppress the production of IL-8 from monocytes via the suppression of neutrophil function.

We investigated the influence of fosfomycin (FOM) on the production and the mRNA expression of interleukin-8 (IL-8) by monocytes. In the incubation of whole blood stimulated by N-Formyl-Met-Leu-Phe (FMLP), FOM significantly suppressed the production and the mRNA expression of IL-8 by monocytes and its inhibitory action was concentration-dependent (FOM: 50-200 microg/ml). However, FOM did not influence the production and the mRNA expression of IL-8 in the incubation of fractionated mononuclear cell stimulated by FMLP. The supernatant of FMLP-stimulated polymorphonuclear leukocyte (PMNL) could induce the mRNA expression of IL-8 by monocyte. The supernatant of FMLP-stimulated PMNL which was pre-treated with FOM significantly (P < 0.05) inhibited the expression of IL-8 mRNA by monocyte. Moreover, FOM suppressed the production of leukotriene B4 (LTB4) from neutrophil in a concentration-dependent manner. When LTB4 was added to the fractionated mononuclear cells directory, the expression of IL-8 mRNA was enhanced (P < 0.05). The present study indicated that FOM suppress the production of LTB4 from neutrophils and suppress the expression of IL-8 mRNA by LTB4 from monocytes. It was also demonstrated that LTB4 produced by neutrophil is one of the factor which promotes the expression of IL-8 mRNA in monocytes.

Anti-Bacterial Agents↗

Paradoxical lateral suppression in the dolphin's auditory system: weak sounds suppress response to strong sounds.

A paradoxical phenomenon was found in the auditory system of dolphins: weak sounds suppressed the brain responses to much stronger sounds. This occurred when the brain evoked potentials to rhythmic sound amplitude modulations were recorded. The response was markedly suppressed by addition of another sound of higher frequency and down to 40 dB lower intensity than the amplitude-modulated signal. Only the sustained rhythmic response was suppressed while transient on-response was not, thus indicating that the suppression influenced the ability of evoked potentials to follow rapid amplitude modulations. This prevents weak sounds from being masked by stronger ones. It may help a dolphin to perceive weaker echo-signals in the background of stronger emitted pulses.

Acoustic Stimulation↗

CER suppression, passive-avoidance learning, and stress-induced suppression of drinking in the Syracuse high- and low-avoidance strains of rats (Rattus norvegicus).

The Syracuse strains of Long-Evans rats were selectively bred for good (SHA) or poor (SLA) avoidance learning in a two-way shuttle box, which resulted in a phenotypic difference that is correlated with behavior patterns indicative of emotional reactivity, SLA animals showing evidence of greater emotional reactivity than SHA animals. The first three experiments examined conditioned suppression of bar pressing and compared paired and unpaired conditioned- and unconditioned-stimulus presentations to evaluate the influence of conditioning versus primary aversive stimulation on baseline responding. SLA animals acquired conditioned suppression faster than SHA animals and also showed greater suppression of baseline responding than SHA animals. In Experiment 4, SLA animals learned a passive-avoidance task faster than SHA animals. In Experiment 5, SLA animals showed greater stress-induced suppression of drinking a weak quinine solution than SHA animals. These data are consistent with the hypothesis that SLA animals are more emotionally reactive than SHA animals.

Animals↗

DNA damage-induced expression of p53 suppresses mitotic checkpoint kinase hMps1: the lack of this suppression in p53MUT cells contributes to apoptosis.

DNA damage induced by the topoisomerase I inhibitor irinotecan (CPT-11) triggers in p53(WT) colorectal carcinoma cells a long term cell cycle arrest and in p53MUT cells a transient arrest followed by apoptosis (Magrini, R., Bhonde, M. R., Hanski, M. L., Notter, M., Scherübl, H., Boland, C. R., Zeitz, M., and Hanski, C. (2002) Int. J. Cancer 101, 23-31; Bhonde, M. R., Hanski, M. L., Notter, M., Gillissen, B. F., Daniel, P. T., Zeitz, M., and Hanski, C. (2006) Oncogene 25, 165-175). The mechanism of the p53-independent apoptosis still remains largely unclear. Here we used five p53WT and five p53MUT established colon carcinoma cell lines to identify gene expression alterations associated with apoptosis in p53MUT cells after treatment with SN-38, the irinotecan metabolite. After treatment, 16 mitosis-related genes were found to be expressed at least 2-fold stronger in the apoptosis-executing p53MUT cells than in the cell cycle-arrested p53WT cells by oligonucleotide microarray analysis. One of the genes whose strong post-treatment expression was associated with apoptosis was the mitotic checkpoint kinase hMps1 (human ortholog of the yeast monopolar spindle 1 kinase). hMps1 mRNA and protein expression were suppressed by the treatment-induced and by the exogenous adenovirus-coded p53 protein. The direct suppression of hMps1 on RNA level or inhibition of its activity by a dominant-negative hMps1 partly suppressed apoptosis. Together, these data indicate that the high expression of mitotic genes in p53MUT cells after SN-38 treatment contributes to DNA damage-induced apoptosis, whereas their suppression in p53WT cells acts as a safeguard mechanism preventing mitosis initiation and the subsequent apoptosis. hMps1 kinase is one of the mitotic checkpoint proteins whose expression after DNA damage in p53MUT cells activates the checkpoint and contributes to apoptosis.

Antineoplastic Agents, Phytogenic↗

Immune suppression in vivo with antigen-modified syngeneic cells. I. T-cell-mediated suppression to the terpolymer poly-(Glu, Lys, Phe)n.

The palmitoyl derivative of the linear polypeptide of poly-(L-Glu-L-Lys-L-Phe)n (GLphi) can be coupled to spleen cells directly. The intravenous administration of 2 X 10(5)--3 X 10(7) GLphi-coupled syngeneic spleen cells induces GL-phi-specific suppressor T cells in C57BL/6 nonresponder mice. The suppression is antigen specific and can be detected by the inhibition of the primary GLphi plaque-forming cell response to challenge with GLphi-fowl gamma globulin. The number of inducer cells required for suppression carry less than 0.1 microgram of antigen. Spleen cells from tolerized mice can transfer suppression to normal syngeneic recipients. The suppression is cyclophosphamide sensitive and the suppressor cells bear the Thy 1.2 marker. This method of inducing antigen-specific suppressor cells may be generally applicable to other antigen systems.

Animals↗

Feedback suppression of the immune response in vitro. II. IgVH-restricted antibody-dependent suppression.

Feedback suppression of the primary humoral immune response to sheep erythrocytes (SRBC) in vitro was induced with cell-free supernate material derived from antigen-(SRBC) activated B (sIg+) cells. This soluble products bears Ig determinants and binds to the eliciting antigen (SRBC). The activity of this antibody in suppressing anti-SRBC plaque-forming cell responses is restricted to spleen cell cultures containing B cells sharing VH genes with the B cells producing the suppressive antibody. The anti-hapten (trinitrophenyl) response to derivatized SRBC is not affected by antigen-primed B cells or their products. These data are compatible with suppression being mediated by anti-antigen antibody, either (a) via blockade of different SRBC epitopes recognized by a limited set of B cell clones in each mouse strain, (b) via triggering of an anti-idiotypic response, either antibody or suppressor T cell in nature, restricted to activity in cultures containing B cells sharing VH structures with the original antibody, or (c) via interference by preformed antibody with T cell help directed at idiotype bearing B cells.

Animals↗