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At least 613 records · Page 34Linked to original sources
PubMed1975

Reversal by cyclophosphamide of tolerance in contact sensitization. Tolerance induced by prior feeding with DNCB.

Tolerance to DNCB induced by feeding guinea-pigs with the same hapten has been reversed by a single treatment with cyclophosphamide. This is paralleled by a return of the ability of T cells to proliferate in the draining lymph node following sensitization. Certain quantitative differences between this system and that previously described using intravenous DNBSO3 have been revealed. These may indicate some difference between these two mechanisms of tolerance induction.

Animals↗
PubMed2001

Post-load glucose measurements in oral glucose tolerance tests correlate well with 1,5-anhydroglucitol, an indicator of overall glycaemic state, in subjects with impaired glucose tolerance.

Using both cross-sectional and longitudinal methods, we investigated the relationship between post-load serum glucose concentration in a 75 g oral glucose tolerance test (OGTT) and overall glycaemic state in subjects with impaired glucose tolerance (IGT). Glycaemic state was assessed by measuring glycated haemoglobin (HbA1c) and the serum concentration of 1,5-anhydroglucitol (1,5-AG). In the cross-sectional study, the concentration of 1,5-AG, while remaining within a normal range, was reduced to a degree proportional to the post-load glycaemic level. Although the correlation between HbA1c and post-load plasma glucose was relatively weak (r=0.281, P<0.001), a significant inverse correlation (r=-0.824, P<0.0001) was found between 1,5-AG and mean post-load plasma glucose concentration in 211 subjects with IGT. Fasting plasma glucose (r=-0.539, P<0.0001) and 2 h plasma glucose (r=-0.621, P<0.0001) were correlated with 1,5-AG less strongly than was post-load glycaemia. Both 1,5-AG and HbA1c were correlated weakly but significantly with the fasting insulin concentration. In the longitudinal study we measured 1,5-AG and mean post-load plasma glucose with an OGTT once yearly for 10 years in 15 subjects with IGT. Strong inverse correlations were seen between 1,5-AG and mean post-load plasma glucose in each subject (range of r values among subjects of -0.584 to -0.978). These findings suggest a close relationship between post-load plasma glucose concentration measured by OGTT and overall glycaemic state in subjects with IGT.

Adult↗
PubMed1975

Depressive symptoms and the glucose tolerance test and insulin tolerance test.

Patients with severe depression have been observed previously to have a reduced rate of glucose utilization accompanied by elevated serum insulin levels during the intravenous glucose tolerance test (GTT) and a reduced metabolic responsiveness to exogenous insulin during the insulin tolerance test (ITT). These abnormalities were less obvious in patients with neurotic depression as compared to patients with severe endogenous or "psychotic" depression. To evaluate more fully the relationships of depressive symptomatology to these metabolic abnormalities, patients were rated by nursing staff on a short clinical rating scale (SCRS) and by a psychiatrist on the Brief Psychiatric Rating Scale (BPRS) at the time the metabolic measurements were made. Patients were given the GTT and the ITT once when they were off medication and symptomatic and then again 3 to 8 weeks later when symptoms had decreased following amitriptyline treatment. Fasting serum-free fatty acid levels (FFA) had a significant positive correlation to rating of anxiety. Fasting levels of glucose, insulin, and human growth hormone (HGH) did not significantly correlate to any of the ratings. A decreased rate of glucose utilization (k) correlated significantly with increased ratings of motor retardation, emotional withdrawal, and blunt affects, but not to other depressive symptoms. The responsiveness of FFA and HGH during the ITT was significantly less in patients with more severe symptomatology; responsiveness improved when those patients improved. Neither incorrelated to the ratings. These data suggest that within the sydrome of depression, increased FFA is realated to anxiety, decreased glucose utilization is related to motor retardation, emotional withdrawal, and blunt affect, and that decreased FFA and HGH responsiveness to insulin is a nonspecific correlate of the general depressive syndrome.

Anxiety↗
PubMed1992

Do impaired glucose tolerance and diabetes mellitus interfere with the interpretation of the growth hormone response to the oral glucose tolerance test?

1. The ability of glucose to suppress growth hormone (GH) secretion is well known and the glucose test is widely used for the diagnosis of acromegaly. However, when suspected acromegaly is associated with diabetes mellitus (DM) or impaired glucose tolerance (IGT) the interpretation of the GH response to the oral glucose tolerance test (OGTT) may be difficult. Recently, Hattori et al. (Journal of Clinical Endocrinology and Metabolism, 70: 771-778, 1990), using a highly sensitive (1.5 ng/l) polyclonal antibody-based immunoenzymometric assay, found no differences in the GH response to glucose load among control, IGT and DM patients. 2. We employed a less sensitive (100 ng/l) but monoclonal antibody-based immunoenzymometric assay to measure the serum GH levels of 19 normal subjects, 11 patients with DM and 11 patients with IGT to determine the effect of glucose intolerance on the GH response to the OGTT. 3. Complete suppression of GH (< 0.1 microgram/l) was achieved in 73% of the controls with a mean nadir of 0.17 +/- 0.16 microgram/l (range, < 0.1-0.6 microgram/l). GH was completely suppressed in 82% of the diabetics with a mean nadir of 0.58 +/- 1.21 micrograms/l (range, < 0.1-4.0 micrograms/l). However, complete suppression occurred in only 27% of the IGT patients with a nadir of 1.09 +/- 2.08 micrograms/l (range, < 0.1-7.0 micrograms/l), which was statistically higher than observed for controls and diabetics. 4. We conclude that plasma GH levels after glucose loading of IGT patients should be interpreted with caution because an abnormal response can be detected when some sensitive immunometric assays are employed.

Adolescent↗
PubMed1992

Tolerance and cross-tolerance to the activating effects of 3,4-methylenedioxymethamphetamine and a 5-hydroxytryptamine1B agonist.

Previous studies indicate that 3,4-methylenedioxymethamphetamine (MDMA) produces locomotor hyperactivity in rats by increasing the presynaptic release of serotonin (5-HT). Interactions between MDMA and 5-HT receptor antagonists suggest that the activating effects of MDMA are mediated via 5-HT1-like receptors. In order to assess the contribution of particular 5-HT receptor subtypes to the behavioral effects of MDMA, the present studies examined the development of tolerance and cross-tolerance to the behavioral effects of MDMA and selective 5-HT receptor agonists. In the first study, rats were pretreated with saline, a 5-HT1A receptor agonist (8-hydroxy-2-(di-n-propylamino)tetralin, 1.0 mg/kg), a 5-HT1B receptor agonist [5-methoyx-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole butane dioate (RU24969), 2.5 mg/kg] or a 5-HT1C/5-HT2 receptor agonist (2,5-dimethoxy-4-iodoamphetamine, 1.0 mg/kg) twice daily for 3 days. The behavioral response to S-MDMA (3.0 mg/kg) was assessed 36 hr after the last pretreatment injection. Pretreatment with RU24969 antagonized the activating effects of S-MDMA. In contrast, pretreatment with 2,5-dimethoxy-4-iodoamphetamine did not alter the response to S-MDMA, and pretreatment with 8-hydroxy-2-(di-n-propylamino)tetralin reduced the activity of both control and S-MDMA-treated animals. In the second study, rats were pretreated with saline or RS-MDMA (10 mg/kg), twice daily for 4 days. The behavioral response to saline, S-MDMA (3.0 mg/kg), RU24969 (2.5 mg/kg) or S-amphetamine (1.0 mg/kg) was assessed 36 hr after the last pretreatment injection.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Methylenedioxyamphetamine↗
PubMed1992

[How tolerant are partial dose values? Some additional remarks on the concept of a tolerance dose].

By means of the NSD formula and its modifications (CRE, TDF) evaluated from radiotherapy experience by Ellis, it is possible to estimate the acceptance of applied radiotherapy and fractionation scheme. Because the parameters of the Ellis formula are calculated from patients data, they show a dispersion as usually in biological systems. These dispersions are considered as entrance error. In mathematical transformations errors are multiplied according to the principle of superposition of errors. Especially when judging tolerance values of organs of risk the dispersion is quite important. The problem of dispersion of resulting partial tolerance values is demonstrated by some examples of clinical cases.

Algorithms↗
PubMed1988

Spinal infusion of opiate and alpha-2 agonists in rats: tolerance and cross-tolerance studies.

Intrathecal morphine or ST-91, an alpha-2 agonist, produce potent antinociception in a number of animal models. Using osmotic minipumps and a new Y-catheter technique, we show that chronic intrathecal (i.t.) infusion of morphine (2, 6 or 20 nmol/microliter/hr) or ST-91 (3, 10 or 30 nmol/microliter/hr) in rats produces a dose-dependent increase in hot-plate latency 1 day after pump implant. By 4 to 5 days after initiation of chronic infusion of either drug, hot-plate latencies do not differ from saline-infused controls. Rats rendered tolerant to one of the three chronic i.t. morphine doses (2, 6 or 20 nmol/microliter/hr) and tested at 7 days after initiation of infusion with a bolus i.t. dose of morphine, show a dose-dependent rightward shift in hot-plate dose-response curves. The two lower doses of chronic i.t. infusions of morphine produce parallel shifts of the subsequent i.t. administered morphine dose-response curves, but the highest chronic i.t. dose of morphine (20 nmol/microliter/hr) produces a significantly greater slope of the subsequent i.t. administered morphine dose-response curve. Animals exposed to chronic i.t. infusion of one of three doses of ST-91 (3, 10 or 30 nmol/microliter/hr) display a parallel, dose-dependent rightward shift to a subsequent bolus i.t. injection of ST-91. Rats rendered tolerant to chronic i.t. infusions of ST-91 showed no difference in the response to i.t. administered morphine hot-plate dose-response curves as compared to saline infused controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1979

Role of self carriers in the immune response and tolerance. IV. Active T cell suppression in the maintenance of B cell tolerance to a "T-independent" antigen.

Previous studies indicated that T cells are required for tolerance induction by hapten-modified syngeneic spleen cells (TNP-SC) in vivo. The role of T cells in the maintenance of this unresponsive state has been examined herein. By three criteria--limiting dilution precursor analysis, removal of T cells by anti-Thy-1 + C, and direct mixing experiments--we show that T cells are required for the continued suppression of the B cell response to the T-independent antigen, TNP-POL. Suppressor cells can also be induced by TNP-teratoma cells, which lack detectable H-2 antigens. Both anti-Ly-1 + C and anti-Ly-2 + C treatment reversed suppression induced by TNP-SC. These results demonstrate that normal B cell reactivity is present in the spleens of mice rendered tolerant by haptenated self, but that Ly-1,2,3 or Ly-1 + Ly-2,3 suppressor T cells prevent their responsiveness.

Animals↗
PubMed1982

Induction of transplantation tolerance in guinea pigs by spleen allografts. II. Responses in the mixed leukocyte reaction correlate with the tolerant state.

We have developed a model for the induction of transplantation tolerance in the guinea pig by vascularized spleen allografts. Spleen allografts from strain 13 to strain 2 hosts frequently survived in healthy recipients without clinical GVHD or induced clinical GVHD. (2 x 13)F1 to strain 2 spleen allografts survived indefinitely without inducing GVHD. In contrast, strain 2 spleen allografts were rejected by strain 13 hosts. An excellent correlation was observed between the clinical course and the degree of reactivity to donor strain stimulator cells in the MLR. Animals that had rejected their grafts had normal or enhanced proliferative responses in the MLR. Strain 2 hosts with long-term surviving strain 13 or (2 x 13)F1 grafts had markedly suppressed anti-13 responses. Animals with GVHD had a suppressed MLR toward donor strain stimulator cells with simultaneous reactivity to host strain stimulator cells. Cells capable of suppressing the response of normal host strain cells to donor strain stimulators were present in some long-term surviving animals and may be responsible in part for the maintenance of the tolerant state.

Animals↗
PubMed1984

Tolerance and the H-Y antigen: Requirement for male T cells, but not B cells, to induce tolerance in neonatal female mice.

Transplantation tolerance of the H-Y antigen may be induced and transferred by lymphoid cells, but not by nonlymphoid cells. In this study we have demonstrated that amongst lymphoid cells, T cells--but not B cells or macrophages--are capable of inducing transplantation tolerance. In contrast, all three populations express sufficient amounts of immunogenic H-Y antigen to sensitize adult female mice to a subsequent male skin graft, as demonstrated by the second-set reaction.

Animals↗
PubMedDate not supplied

Development of tolerance to benzodiazepines. II. Baclofen effect on the activity of rats during tolerance to the sedative action of nitrazepam and oxazepam.

It was demonstrated that baclofen, a GABA-ergic agent, exerted a sedative effect in rats with tolerance to the sedative action of oxazepam and nitrazepam induced by administration of these drugs during several weeks. After one dose baclofen alone reduced the motor activity of rats without potentiating the effects of benzodiazepines. During long-term administration of baclofen tolerance developed also to its sedative action.

Animals↗
PubMed1983

Tolerance to d-amphetamine and lack of cross-tolerance to other drugs in rats under a multiple schedule of food presentation.

Rats were trained under a multiple fixed-ratio 30-response, fixed-interval 5-min schedule of food presentation. Dose-response curves for d-amphetamine, pentobarbital, chlordiazepoxide, ethanol, morphine, phencyclidine and delta 9-tetrahydrocannabinol were determined. At low doses, pentobarbital and chlordiazepoxide produced small increases in response rates, whereas other drugs had no effect. At high doses, all drugs produced decreases in both fixed-ratio and fixed-interval rates of responding. With the exception of ethanol, all drugs produced decreases in fixed-ratio rates at lower doses than those which decreased fixed-interval rates. After the initial dose-response determinations, all animals received a single daily dose of d-amphetamine (10 mg/kg) after the behavioral session for 112 d-amphetamine (10 mg/kg) after the behavioral session for 112 consecutive days. Chronic postsession treatment with d-amphetamine produced a progressive decrease in rate of responding. Dose-response curves for all the drugs were redetermined after 2 weeks of chronic d-amphetamine treatment. During chronic d-amphetamine treatment, there was tolerance to the rate-decreasing effects of d-amphetamine. No cross-tolerance was observed for the other drugs tested.

Animals↗
PubMed1981

Mice tolerant to nitrous oxide are not tolerant to barbiturates.

Mice continuously exposed to 50% nitrous oxide for 2 weeks or more become tolerant to nitrous oxide, as measured by an 8% to 19% increase in their nitrous oxide ED50 (the dose required to abolish the righting reflex in 50% of the animals). Control mice tolerant to nitrous oxide were given intraperitoneal injections of secobarbital (50 mg/kg), phenobarbital (120 mg/kg), or pentobarbital (55 or 65 mg/kg). Sleep onset times, sleep times, and serum levels of barbiturates upon awakening did not differ between the two groups. These results suggest that nitrous oxide and barbiturates do not share a common mechanism of action.

Anesthesia, Inhalation↗
PubMed1995

Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases.

Approximately 10% of peripheral CD4+ cells and less than 1% of CD8+ cells in normal unimmunized adult mice express the IL-2 receptor alpha-chain (CD25) molecules. When CD4+ cell suspensions prepared from BALB/c nu/+ mice lymph nodes and spleens were depleted of CD25+ cells by specific mAb and C, and then inoculated into BALB/c athymic nude (nu/nu) mice, all recipients spontaneously developed histologically and serologically evident autoimmune diseases (such as thyroiditis, gastritis, insulitis, sialoadenitis, adrenalitis, oophoritis, glomerulonephritis, and polyarthritis); some mice also developed graft-vs-host-like wasting disease. Reconstitution of CD4+CD25+ cells within a limited period after transfer of CD4+CD25- cells prevented these autoimmune developments in a dose-dependent fashion, whereas the reconstitution several days later, or inoculation of an equivalent dose of CD8+ cells, was far less efficient for the prevention. When nu/nu mice were transplanted with allogeneic skins or immunized with xenogeneic proteins at the time of CD25- cell inoculation, they showed significantly heightened immune responses to the skins or proteins, and reconstitution of CD4+CD25+ cells normalized the responses. Taken together, these results indicate that CD4+CD25+ cells contribute to maintaining self-tolerance by down-regulating immune response to self and non-self Ags in an Ag-nonspecific manner, presumably at the T cell activation stage; elimination/reduction of CD4+CD25+ cells relieves this general suppression, thereby not only enhancing immune responses to non-self Ags, but also eliciting autoimmune responses to certain self-Ags. Abnormality of this T cell-mediated mechanism of peripheral tolerance can be a possible cause of various autoimmune diseases.

Animals↗
PubMed1994

Oral tolerance in humans. T cell but not B cell tolerance after antigen feeding.

The purpose of this study was to investigate whether oral tolerance, defined as Ag-specific immunologic unresponsiveness after Ag feeding, could be induced in humans after prolonged Ag ingestion. Eight adult volunteers ingested a total dose of 0.5 g of keyhole limpet hemocyanin (KLH) followed by subcutaneous immunization with KLH. Eight controls received only the subcutaneous immunization. In the group fed KLH, there was a significant reduction in KLH-specific T cell proliferation (p = 0.04) and delayed skin test responses (p = 0.07) to KLH. KLH ingestion alone did not induce significant levels of Abs in either serum or secretions. However, after the subsequent subcutaneous immunization, the number of circulating IgG and IgM anti-KLH-producing cells, the titers of serum IgG, IgA, and IgM anti-KLH Abs, and the titers of IgA anti-KLH Abs in saliva and intestinal secretions were significantly greater in the KLH-fed group than in the nonfed group. We conclude that KLH feeding induced systemic T cell tolerance, but B cell priming, at both systemic and mucosal sites. These studies support the concept of using Ag feeding as a treatment for certain immune-mediated diseases.

Administration, Oral↗
PubMed1994

Tolerance to rat liver allografts. I. Differences between tolerance and rejection are more marked in the B cell compared with the T cell or cytokine response.

Liver allografts in the fully allogenic combination of LEW donor liver to DA recipient (LEW-->DA) are spontaneously tolerated (TOL) with no requirement for immunosuppression, while DA-->LEW allografts are rejected in 12-15 days (REJ). We investigated the mechanism of tolerance induction by identifying differences between TOL and REJ grafts from day 1 to day 9 after transplantation and in normal livers and syngeneic liver graft controls. Infiltrating cell populations were counted after immunohistochemical staining of liver graft sections. There were occasional minor differences between TOL and REJ grafts in the T cell or CD11b/c+ (monocyte/macrophage/granulocyte) infiltrate. In contrast, there was a major difference in B cell infiltrate between TOL and REJ liver grafts. Membrane IgD+ cells were significantly greater in TOL (1796 +/- 225) versus REJ (569 +/- 281) (P = 0.004) portal tracts, as were B220+ cells (1086 +/- 100 vs. 181 +/- 105, P = 0.0004) and CD45RC+ cells (2317 +/- 456 vs. 597 +/- 194, P = 0.004). IgG1, IgG2a, IgM, and IgD deposition in liver allografts, identified by immunohistochemical staining of tissue sections, revealed no IgG or IgD in normal rat liver and low levels of IgM. Deposition of IgG1 was observed in REJ but not in TOL liver on days 7 and 9. IgM was increased in both TOL and REJ liver and appeared to be associated mainly with hepatocytes in REJ and with infiltrate in TOL liver. There was a parallel increase in IgG1-expressing plasma cells in the spleen and lymph nodes of REJ but not TOL animals. Cytokine mRNA was analyzed by reverse transcription and semiquantitative polymerase chain reaction amplification of liver RNA. Increased levels of IL-2, IL-4, IL-6, IL-10, TNF-alpha, transforming growth factor-beta, and IFN-gamma were observed, with similar levels of expression in TOL compared with REJ liver. Cytokine mRNA in syngeneic grafts was not different from normal except for IL-6 and transforming growth factor-beta, which were increased. There is no major difference in the T cell component of the infiltrate or in the extent of upregulation of cytokine mRNA between TOL and REJ grafts. There is a major difference in the B cell compartment, with more B cells in TOL livers and deposition of IgG1 in REJ grafts.

Animals↗
PubMed1979

Immunologic tolerance to allergenic protein determinants: properties of tolerance induced in mice treated with conjugates of protein and a synthetic copolymer of D-glutamic acid and D-lysine (D-GL).

Conjugates of proteins and the synthetic copolymer of D-glutamic acid and D-lysine (protein-D-GL) reproducibly induce significant unresponsiveness to the protein antigens in experimental mice. Proteins studied include ovalbumin and antigen E of ragweed extract, the major allergen of ragweed pollen. The unresponsive state 1) can be induced in both unsensitized and previously sensitized experimental animals, 2) is selectively confined to responses of the IgE antibody class, 3) is long lasting, and 4) is highly antigen specific. IgE antibody responses can also be suppressed by administering comparable doses of unconjugated protein alone; however, the unresponsive state induced in this manner is only transient and rebound production of IgE antibody is often observed. Results from the studies of the cellular basis of the protein-D-GL induced unresponsiveness demonstrate that 1) protein-D-GL conjugates do not induce unresponsiveness at the level of protein-specific B cells, 2) tolerance is not induced by virtue of a detectable antigen-specific suppressor T cell mechanism, 3) tolerance is most probably induced in the antigen-specific helper T cell populations. The significant IgE-selective and antigen-specific tolerogenic activity of protein-D-GL conjugates make these compounds potential candidates for use as therapeutic agents in the treatment of IgE-mediated human allergic disorders induced by protein allergens.

Allergens↗
PubMed2004

HSP60 induces self-tolerance to repeated HSP60 stimulation and cross-tolerance to other pro-inflammatory stimuli.

In addition to their primary function as intracellular chaperone proteins, the immunomodulatory properties of heat shock proteins (HSP), including their role as adjuvants for vaccines, have become a focus of intense research interest. Interestingly, the effect of chronic exposure to an endogenous immunomodulator and initiator of inflammation such as autologous HSP60 has as yet remained uncharacterized. In this study, we demonstrate that pretreatment of monocytes with human HSP60 results in a suppression of TNF-alpha production on restimulation with HSP60. Furthermore, desensitization with HSP60 inhibits TNF-alpha expression in these cells in response to LPS stimulation, thereby inducing "cross-tolerance". In contrast to TNF-alpha suppression, IL-1beta expression was augmented in HSP60-pretreated monocytes on restimulation, while being suppressed in THP-1 cells. Addition of an anti-IL-10 neutralizing antibody had no significant effect on HSP60- or LPS-induced tolerance.HSP60 priming of monocytes also results in significant down-regulation of HLA-DR, CD86 and Toll-like receptor 4 expression, but minimally up-regulates CD80 expression, similar to that previously reported with LPS. By identifying a previously unrecognized "tolerizing" effect of extended exposure to autologous HSP60 on the innate immune system, as opposed to its recently identified pro-inflammatory stimulatory capacity, this study highlights a further level of complexity of our understanding of the biological activities of HSP.

B7-1 Antigen↗