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Results for “Models, Immunological”

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At least 127 records · Page 7Linked to original sources

Chlorpyrifos exacerbating pemphigus vulgaris: a preliminary report and suggested in vitro immunologic evaluation model.

BACKGROUND: There is accumulating evidence on the role of pesticides in the etiology of pemphigus vulgaris (PV). OBJECTIVE: To determine whether chlorpyrifos, an organophosphate pesticide, is involved in the immunopathology of PV. METHODS: Normal human skin biopsy specimens incubated with progressively diluted chlorpyrifos solutions were used as indirect immunofluorescence substrates for sera from two PV patients previously exposed to the agent and from healthy controls. Involvement of T-cell lymphocytes was assessed by release of interferon-g in the presence of chlorpyrifos. RESULTS: In one PV patient, immunofluorescence was strongly positive for the specimen incubated with the pesticide and weakly positive for the specimen incubated with medium alone. Immunofluorescence was negative in the patient under immunosuppression with prednisolone and in all controls. Both patients tested positive on interferon-g assay; controls tested negative. CONCLUSIONS: Findings suggest an immunopathogenic role of chlorpyrifos in PV. Interferon-g cytokine assay with the pesticide combined with immunofluorescence tests may provide an in vitro diagnostic tool in suspected pesticide-induced/exacerbated pemphigus.

Adult↗

Mucosal immunology and models of mucosal HIV infection.

The mucosa associated lymphoid tissue regulates and coordinates immune responses against mucosal pathogens. Mucosal tissues are the major targets exposed to HIV during transmission. In this paper we describe in vitro models of HIV mucosal infection using human explants to investigate target cells within this tissue.

Adult↗

[The cluster headache: a clinical model of immunologic receptor pathology?].

It is well established that cluster headache shows impaired functions at their neuroimmunomodulatory system level. Defect in receptor expression for 5-HT, IL-1 and IL-2 have been found in these patients. Sumatriptan, a molecule with agonistic activity for 5-HT1D receptor, truncates cluster headache attacks in 74% of patients. Flow cytometric analysis of monocytes expressing 5-HT receptor in cluster headache patients showed different trends clearly correlated with the clinical response to sumatriptan. Our findings strongly support the concept that cluster headache patients who are non responders to sumatriptan could present a block in their 5-HT receptor possibly due to specific autoantibodies for this receptor site.

Adult↗

Vaccination against cutaneous leishmaniasis in a murine model. II. Immunologic properties of protective and nonprotective subfractions of soluble promastigote extract.

We have previously demonstrated that BALB/c mice can be protected against a fatal infection with Leishmania major by i.p. immunization with a soluble leishmanial antigen (SLA) preparation in conjunction with the adjuvant, Corynebacterium parvum (CP). In this study, SLA was separated into nine distinct fractions by anion exchange liquid chromatography, and the fractions were analyzed for their ability to stimulate T cells obtained from immunized mice, to be recognized by vaccine-induced antibodies, and to induce protective immunity. While all but one of the fractions were recognized by antibodies from SLA + CP immunized mice, only two fractions (fractions 1 and 9) stimulated lymphocytes to produce macrophage-activating factor and elicited significant delayed-type hypersensitivity in vivo. When mice were immunized with the fractions, only fraction 9 stimulated significant immunity (76% protection in seven experiments). Proteins (accounting for 1.3% of the total in SLA) appear to be responsible for the protection elicited with fraction 9, since protease treatment of this fraction destroyed its immunogenicity. Thus, a partially purified protective protein antigen fraction has been obtained and protection with this fraction correlated with cell-mediated immune responses. However, these results also demonstrate that the ability of leishmanial antigens to be recognized by T cells and produce macrophage-activating factor does not in itself predict whether such molecules will induce immunity, suggesting that protective leishmanial antigens may have additional unique properties.

Animals↗

Regeneration through long nerve grafts in the swine model.

We investigated regeneration across a long nerve defect in the swine model to study extensive neural loss and long nerve gap. Most experiments have been conducted in the rodent model that, while an appropriate immunological model, only allows short nerve gaps to be studied. Twelve outbred swine received either an 8-cm ulnar nerve autograft or an allograft without immunosuppression. At 6 and 10 months, histomorphometry of the autografts demonstrated excellent nerve regeneration, while very poor regeneration was noted across the allografts. This confirmed that 8 cm are an adequate challenge independent of the spontaneous regeneration potential of axons seen in rodents. The swine ulnar nerve graft model causes minimal morbidity and will now be used with immunological manipulation of inbred animals.

Animals↗

[Metabolic aspects of multiple sclerosis].

According to the present opinion multiple sclerosis (MS) is caused by a concurreance of various factors. This predisposing factor seem to be related to a disturbance of the lipid- and fatty acid metabolism, characterized by decreased concentrations of polyunsaturated fatty acids (PUFA) and essential fatty acids (EFA) in the plasma, the blood cells, the cerebrospinal fluid (CSF) and white matter of the brain in patients with MS. A disturbed absorption of EFA could be excluded. Now the question arises whether there is a disturbed utilisation of EFA with the consequence of biochemical changes in myelin and blood cells. According to lipid-chemical and lipolytic enzymological studies a disturbance of the fatty acid elongation system as well as primary increased activation of the phospholipase A1 is conceivable. According to the demonstrated results the conception of a metabolic immunological caused generalised defect of the biological membranes - especially those of the myelin sheath and platelets - as predisposing factor for the increased platelet aggregation is possible. Even though these ideas do not yet allow a concrete pathogenetic conclusion, the prostaglandins (PG) might be of importance because their precursors are fatty acids and influence the immune mechanisms. Possibly, new approaches follow from the synopsis of present working hypotheses for an extended biochemical-immunological model of multiple sclerosis. Further immunological and laboratory methods should concentrate on differentiating MS from other diseases of the central nervous system and on diagnosing the disease in its early stage. The results of this work are fully discussed in other publications. Separate prints can be requested from the author.

Fatty Acids, Essential↗

Random changepoint modelling of HIV immunologic responses.

We propose a changepoint model for the analysis of longitudinal CD4 T-cell counts for HIV infected subjects following highly active antiretroviral treatment. The profile of CD4 counts for each subject follows a simple, 'broken stick' changepoint model, with random subject-specific parameters, including the changepoint. The model accounts for baseline covariates. The longitudinal CD4 records are censored at the time of the subject going off-study-treatment. This is a potentially informative drop-out mechanism, which we address by modelling it jointly with the CD4 count outcome. The drop-out model incorporates terms from the CD4 model, including the changepoint. The estimation is done in a Bayesian framework, with implementation via Markov chain Monte Carlo methods in the WinBUGS software. Model selection using DIC indicates that the data support the complex random changepoint and informative censoring model.

Antiretroviral Therapy, Highly Active↗

Cross-reactivity of anti-human chemokine receptor and anti-TNF family antibodies with common marmoset (Callithrix jacchus) leukocytes.

The common marmoset (Callithrix jacchus) is a New World primate species frequently employed for immunological models of human disease. We used flow cytometry to screen a panel of new anti-human antibodies from the HLDA8 workshop to establish cross-reactivity with marmoset peripheral blood mononuclear cells. Seventy-seven antibodies were screened of which nine antibodies showed binding. Cross-reactivity of anti-human monoclonal antibodies with CC and CXC chemokine receptors CCR3, CCR6, CCR7, and CCR8 was demonstrated on untreated marmoset mononuclear cells. Stimulation of marmoset mononuclear cells with ConA and/or PMA-ionomycin resulted in an up-regulated expression of CXCR1, CXCR3, and CXCR4. The expression of TNF-family related molecules TACI and APRIL on marmoset mononuclear cells was also identified. These studies extend the range of cross-reactive antibodies to now include anti-chemokine and anti-TNF family antibodies for this important pre-clinical model species and should provide useful tools for investigation of immunological processes in marmoset monkey models.

Animals↗

A non-immunogenic myasthenia gravis model and its application in a study of transsynaptic regulation at the neuromuscular junction.

A non-immunological model for myasthenia gravis was developed in rats: 'toxin-induced myasthenia gravis'. Rats were injected once every 48 h with 3-5 micrograms alpha-bungarotoxin for periods of up to 5 weeks. This treatment caused weakness, especially of facial muscles. Respiration, however, was unaffected. Miniature endplate potentials and 125I-alpha-bungarotoxin binding in the extensor digitorum longus muscles were severely reduced. Acetylcholine release evoked by electrical and chemical (50 mM KCl) stimulation was higher in diaphragms from alpha-bungarotoxin-treated rats than in those from control animals. Histological investigation of the tibialis anterior muscle provided no evidence that the endplates were enlarged. It is concluded that the activity of acetylcholine receptors influences the rate of transmitter release in the neuromuscular junction and it is suggested that a transsynaptic regulation process may be active in myasthenia gravis. The present animal model for myasthenia gravis seems very suitable for studying such a regulation of transmitter release.

Acetylcholine↗

Some pharmacological properties of tiopronin.

Tiopronin (50 mg/kg) and D-penicillamine (50 mg/kg) do not exhibit anti-inflammatory effects in classic animal models (carragenin oedema, granuloma cotton pellets) but suppress pertussis vaccine oedema, an immunological model, when given with a long-lasting dosing regime. Tiopronin and D-penicillamine also fail to inhibit PG release by phagocytosing leucocytes when the concentrations used were in the same range as human blood levels (5-15 micrograms/ml). Indomethacin (1, 3 and 5 mg/kg) instead significantly inhibits both the in vivo and in vitro models considered. This may imply a different mode of action of both tiopronin and D-penicillamine from indomethacin. Tiopronin also possesses similar effects to D-penicillamine suggesting that their overall anti-rheumatic action may have common elements.

Amino Acids, Sulfur↗

Some thoughts on the reproductive autoimmune failure syndrome (RAFS) and Th-1 versus Th-2 immune responses.

PROBLEM: The concept of immunologically induced reproductive failure has remained very controversial. Especially the question whether abnormal immune function can cause infertility has recently been subject to strong disagreement. This opinion piece is an attempt to reconcile difference of opinion by integrating clinical data from the human experience with well-established experimental models in animals. METHOD OF STUDY: Review of published literature. RESULTS: Experimental animal data, especially in the mouse, have suggested that normal pregnancy requires a switch to an immune response with T helper (Th)-2 preponderance. Recent data from the human experience suggest that infertility, repeated pregnancy loss and certain complications of pregnancy may be the consequence of abnormal Th-1 preponderance. In analogy, to animal models, immunologic reproductive failure in humans, may therefore not be the consequence of specific autoantibody abnormalities or natural killer (NK)-cell abnormalities, but the reflection of a misdirection of a more broadly based immune response. CONCLUSIONS: Under such a model, both diagnosis and treatment of immunologically induced forms of reproductive failure require re-evaluation. Such a model, however, provides a satisfactory explanation for contradictory findings in the human experience that have led to strong disagreements among investigations.

Animals↗