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Biomedical subjects

J G Michael

Publications and source records attributed to J G Michael.

At least 19 recordsLinked to original sources
PubMed2000

Abrogation of oral tolerance by feeding encapsulated antigen.

Results from previous studies have indicated that suppression of immune responses cannot be abrogated once oral tolerance has been established. Using a new methodology, OVA was encapsulated and fed to tolerized BDF1 mice. Results from these studies indicated that although IgG2a titers remained low, total IgG and IgG1 antibody titers were no longer suppressed compared to controls. Furthermore, in vitro splenocyte proliferation was not significantly suppressed in tolerized mice fed encapsulated OVA. To determine whether oral tolerance could be abrogated in other strains of mice, BALB/c mice were tolerized and fed encapsulated OVA. Results from these studies indicated that IgG2a as well as IgG1 and total anti-OVA antibody titers were no longer suppressed. Although splenocyte proliferation did remain significantly suppressed in these mice, IFN-gamma and IL-4 levels were no longer decreased. To the best of our knowledge, this is the first time that abrogation of an established oral tolerance has been demonstrated.

Acrylic Resins↗
PubMed1999

Pepsin-digested peanut contains T-cell epitopes but no IgE epitopes.

BACKGROUND: Peanuts are a common cause of food-induced anaphylaxis and fatalities. Previous studies have demonstrated that rush immunotherapy to crude peanut extract reduces clinical symptoms triggered by oral peanut challenges, but the immunotherapy was associated with an unacceptably high incidence of systemic allergic reactions. One approach to reduce the frequency of allergic reactions would be to use a modified peanut antigen with low allergenic properties. OBJECTIVE: We sought to determine the immunologic characteristics of crude intact peanut extract before and after pepsin digestion. METHODS: We used IgE immunoblotting and assessment of T-lymphocyte responses to intact and peptic digests of peanut extracts. RESULTS: Western blot analysis of sera from 5 subjects with peanut allergy showed multiple IgE-reactive proteins in crude intact peanut extract that were eliminated after pepsin treatment of the peanut extract. In contrast, pepsin-digested peanut induced significant T-cell proliferation responses (stimulation index = 30) in vitro in PBMCs from 7 subjects with peanut allergy, albeit at lower levels than that induced by intact peanut (stimulation index = 66). Furthermore, IFN-gamma production was induced by intact peanut and pepsin-digested peanut in a concentration-dependent manner. Importantly, T-cell lines generated in response to intact peanut also reacted to pepsin-digested peanut, indicating cross-reactive T-cell epitopes in intact and pepsin-digested peanut. CONCLUSION: These findings suggest that pepsin-digested peanut may be useful in peanut immunotherapy because pepsin digestion eliminates IgE reactivity but maintains T-cell reactivity.

Adult↗
PubMed1999

Oral immunization with a Streptococcal pneumoniae polysaccharide conjugate vaccine in enterocoated microparticles induces serum antibodies against type specific polysaccharides.

The authors examined the antibody responses of mice orally immunized with pneumococcal polysaccharide (type 23F) or a pneumococcal polysaccharide conjugated to the outer membrane protein complex of Neisseria meningitides (23F-OMPC). These antigens were administered either in solution or entrapped within microcapsules. Only the mice receiving the encapsulated conjugate vaccine produced significant levels of anti-polysaccharide serum antibodies. These responses, observed after a second oral immunization with the conjugate, were predominantly IgG. Thus, the conversion from a T-cell-independent to a T-cell dependent response, achieved through conjugation was maintained following oral delivery. However, no local secretory IgA anti-polysaccharide response was detected in these mice indicating that while the OMPC carrier augments orally induced IgG responses, it was insufficient for the induction of secretory IgA.

Administration, Oral↗
PubMed1999

Amiodarone in the treatment of junctional ectopic tachycardia after cardiac surgery in children: report of two cases and review of the literature.

Junctional ectopic tachycardia (JET) occurs most frequently after operative repair of congenital heart defects. The mechanism is thought to involve direct trauma to the atrioventricular node and His bundle resulting in an ectopic focus. Several therapeutic methods have been described in the pediatric literature with varying degrees of success and complication rates. Because heart rates may exceed 200 to 300 beats per minute, there may be inadequate time for ventricular filling. Ventricular filling can be further compromised because of the asynchrony between the atria and the ventricles. These factors can lead to significant compromise of cardiovascular function in the postoperative patient. We describe our experience with amiodarone in two patients who developed postoperative JET after repair of congenital heart defects. Dosing regimens and previous experience with amiodarone in patients with JET are reviewed.

Adolescent↗
PubMed1998

Induction of oral tolerance in TGF-beta 1 null mice.

Previous studies have suggested that oral tolerance induction by low doses of Ag is mediated by inhibitory cytokines, particularly TGF-beta 1. To examine the roles of TGF-beta 1 and other inhibitory cytokines in the induction of oral tolerance, TGF-beta 1 null mice and controls were gavaged with 10 to 20 mg (high dose) or 1 mg (low dose) of OVA for 3 days. After immunization with OVA, the in vitro proliferative response of OVA-specific popliteal lymph node cells was assessed. Lymphocytes from all TGF-beta 1 null mice fed high doses of OVA exhibited highly significant suppression compared with controls. A weaker, but still significant, suppression was observed in lymphocytes from the majority of TGF-beta 1 null mice fed low doses of OVA. In addition, supernatants from these lymphocytes exhibited lower levels of IL-4, IL-10, and IFN-gamma than those from water-fed control animals. These results indicate that while TGF-beta 1 may play a role in suppression, inhibitory cytokines are not the exclusive mechanism by which low dose oral tolerance is induced.

Administration, Oral↗
PubMed1997

Oral immunotherapy with short ragweed extract in a novel encapsulated preparation: a double-blind study.

BACKGROUND: In the past, oral immunotherapy with allergens has had limited clinical effectiveness, presumably because of gastrointestinal destruction of allergens. OBJECTIVE: We have developed a new technique for microencapsulating protein antigens that permits them, when given orally, to bypass the stomach and be delivered to the small intestine in a highly immunogenic form. This study's purpose was to confirm the immunologic potency of orally administered short ragweed pollen extracts (SRW) microencapsulated (mSRW) by this new technique and to study the effectiveness of mSRW in controlling the symptoms of ragweed-induced hay fever. METHODS: Twenty-one SRW-sensitive patients were treated with mSRW in a double-blind placebo-controlled study. Serum SRW IgG and IgE antibodies and nasal secretory IgA antibodies were determined. During the ragweed season, symptoms were quantified by symptom-medication scoring. RESULTS: The treated patients had high titers of serum SRW IgG antibodies (1.15 microg/ml at baseline, increasing to 21.21 microg/ml), experienced regulation of the seasonal increase in serum SRW IgE antibodies (+9% vs +59% in placebo-treated patients), and produced a small amount of nasal SRW IgA antibodies. Despite an insubstantial pollen count, the symptom-medication scores in the treated group were lower than those in the placebo group (4.28 vs 6.18, p = 0.059), but the differences were statistically significant only in the subgroup that tolerated high doses (>20 microg of Amb a 1 in 19 of 21 patients, p = 0.04). These effects were accomplished without inducing any systemic reactions with a dose of mSRW (mean, 23.8 microg of Amb a 1) only slightly higher than that used in high-dose subcutaneous immunotherapy. CONCLUSION: Oral mSRW seems a safe, easily administered, and immunologically potent treatment for ragweed-induced hay fever, but its ultimate utility requires further study.

Administration, Oral↗
PubMed1996

Activation patterns of murine T cells after oral administration of an enterocoated soluble antigen.

An orally administered soluble protein antigen, ovalbumin (OVA), enterocoated with an acid-resistant acrylic polymer, induced a strong humoral immune response in BDF1 mice, exhibiting Th2 cell phenotype, typified by increased OVA-specific IgA, IgG1, and IgE antibody responses. This antibody response was accompanied by OVA-specific T cell proliferation response and IL-4 cytokine production. Mice fed enterocoated OVA and administered anti-IL-4 mAb showed a shift of the immune response toward the Th1 cell phenotype as evidenced by increased IFN-gamma production and anti-OVA IgG2a isotype antibody response. Additionally, in mice fed OVA solution and simultaneously administered anti-IL-4, we saw a slight but significant expression of Th1 cell phenotype. In conclusion, our data indicate that the dominance of Th2 cell phenotype in oral immunity is strongly influenced by the production and presence of IL-4.

Animals↗
PubMed1996

Activation patterns of murine B cells after oral administration of an encapsulated soluble antigen.

Oral administration of soluble protein antigen, ovalbumin (OVA), encapsulated by an acid-resistant acrylic polymer, induced a strong immune response in BDF1 mice. Mice fed the encapsulated OVA showed activation of antigen-specific IgA, IgG and IgG1 isotype antibody-secreting cells which migrated to various lymphoid tissues via the common mucosal immune system traffic pathway. The highest number of antigen-specific antibody secreting cells was found in the Peyer's patches isolated from the upper segment of the small intestine, with their numbers declining along the length of the intestinal tract. Oral administration of this product suggests activation of lymphocytes exhibiting Th2 phenotype as shown by OVA-specific IgA and IgG1 isotype antibody responses. In conclusion, we demonstrated that oral administration of encapsulated soluble protein, in the absence of adjuvant, can activate the murine common mucosal immune system.

Administration, Oral↗
PubMed1996

Activation patterns of murine B cells after oral administration of an encapsulated soluble antigen.

Oral administration of soluble protein antigen, ovalbumin (OVA), encapsulated by an acid-resistant acrylic polymer, induced a strong immune response in BDF1 mice. Mice fed the encapsulated OVA showed activation of antigen-specific IgA, IgG and IgG1 isotype antibody-secreting cells which migrated to various lymphoid tissues via the common mucosal immune system traffic pathway. The highest number of antigen-specific antibody secreting cells was found in the Peyer's patches isolated from the upper segment of the small intestine, with their numbers declining along the length of the intestinal tract. Oral administration of this product suggests activation of lymphocytes exhibiting Th2 phenotype as shown by OVA-specific IgA and IgG1 isotype antibody responses. In conclusion, we demonstrated that oral administration of encapsulated soluble protein, in the absence of adjuvant, can activate the murine common mucosal immune system.

Administration, Oral↗
PubMed1996

Immunologic effects of encapsulated short ragweed extract: a potent new agent for oral immunotherapy.

BACKGROUND: Oral allergen immunotherapy with conventional allergens has not been a useful mode of treatment because of the lack of potency of allergens when administered by this route. OBJECTIVE: To study the immunologic potency of short ragweed pollen extracts microencapsulated by a new technique administered orally to short ragweed pollen-sensitive humans and to establish the dose of oral microencapsulated short ragweed pollen extract required for these effects. METHODS: Nine short ragweed pollen-sensitive patients were treated with a new oral agent for immunotherapy, microencapsulated short ragweed pollen extract, in an open study. The effectiveness of this treatment was determined by comparison to a group of nine matched short ragweed pollen-sensitive patients who received no treatment. Treated patients developed high titers of short ragweed-specific IgG and IgE antibodies and their expected seasonal increase in IgE antibodies was regulated. The dose of microencapsulated short ragweed pollen extract required to achieve these effects was only slightly higher than the dose of short ragweed pollen extract used in high dose subcutaneous immunotherapy. Furthermore, this dose was achieved in 7 weeks. There were no side effects other than mild gastrointestinal ones. The nine treated patients fared clinically better during the ragweed season than the untreated patients in this open study. CONCLUSION: This study suggests that allergens microencapsulated by this new technique may make oral immunotherapy a practical mode of treatment.

Adult↗
PubMed1995

Effect of in vivo depletion of CD4+ and CD8+ cells on the induction and maintenance of oral tolerance.

The role of CD8+ and CD4+ cells in the generation and maintenance of high-dose oral tolerance has been investigated. Mice depleted of CD8+ cells prior to or subsequent to oral tolerization with OVA continued to express suppressed humoral and/or T cell proliferative responses to the homologous antigen. To assess the effect of CD4+ cell depletion on oral tolerance, mice were depleted of CD4+ cells prior to or subsequent to oral tolerization with OVA. After 50% regeneration of CD4+ cells was achieved, OVA-immunized mice produced anti-OVA immune responses that were comparable to those of water-fed control mice. Thus, under our experimental conditions the presence of CD4+ but not CD8+ cells is required to both establish and maintain oral tolerance.

Administration, Oral↗
PubMed1995

The influence of antigen digestion on orally induced immunity and tolerance.

1. Pepsin-digested form of OVA has approximately the same molecular weight as native OVA, but differs in charge and isoelectric focusing point. 2. Pepsin-treated OVA retains most of the native OVA T- and B-cell determinants. 3. Delayed-type hypersensitivity response is suppressed when pepsin-treated OVA is administered i.p. to naive mice. 4. Cimetidine treatment of mice prior to ingestion of OVA shows decreased tolerance, while oral administration of pepsin-treated OVA to cimetidine-treated mice leads to a complete immune unresponsiveness; this suggests an important role for gastric digestion in orally induced immune tolerance.

Administration, Oral↗
PubMed1994

Enhancement of CTL response induced by a viral peptide using cationized BSA, a Th1-stimulating adjuvant.

We have recently shown that it is possible to activate cytotoxic T cells (CTL) in vivo with HSV-1 glycoprotein B H-2Kb-restricted peptide (gB peptide) independent of CD4+ T cell help. Here we report that the gB peptide-specific CTL response is significantly enhanced when mice are immunized with a mixture of gB peptide and cationized BSA (cBSA). The latter molecule is a positively charged form of the native BSA molecule that stimulates CD4+ T cells to produce cytokines characteristic of Th1 cells. The cBSA-enhanced CTL response required the presence of CD4+ T cells, but it did not require stimulation in vitro by antigen or exogenous cytokines. gB peptide/cBSA-activated LN cells transcribed IL-2 and IFN-gamma, but only IL-2 was essential for CTL development. Our data demonstrate that while activation of CTL may occur in the absence of CD4+ cells, cytokines produced by CD4+ Th1 cells provide stimulatory signals during CTL maturation. Thus, cotreatment with a substance that activates Th1 CD4+ cells may be useful for achieving maximal CTL responsiveness.

Adjuvants, Immunologic↗
PubMed1993

Herpes simplex virus class I-restricted peptide induces cytotoxic T lymphocytes in vivo independent of CD4+ T cells.

Cytotoxic T cells were induced in vivo by immunizing C57BL/6 mice with a single dose of a short synthetic peptide representing amino acid residues 497-507 from HSV-1 glycoprotein B. Primed lymph node cells did not require in vitro boosting with peptide and APC for CTL detection. The CTL were CD8+ and H-2b restricted. They were capable of lysing target cells exogenously sensitized with peptide or endogenously processed glycoprotein B. Virus-primed CTL produced an anamnestic response in vivo upon peptide challenge, indicating that peptide-specific CTL may be relevant to infection. The requirement of CD4+ T cells for CD8+ CTL activation was investigated by depleting CD4+ cells in vivo with GK1.5 mAb. CD4+ T cell depletion did not abrogate CTL generation. These results suggest that glycoprotein B peptide 497-507 activates CD8+ CTL in vivo in a manner independent of CD4+ T cells. This is the first study in which a class I-restricted peptide derived from a HSV protein was used to activate CTL in vivo, and in which a synthetic peptide was shown to activate CTL independent of CD4+ T cell help. Our data are relevant to viral vaccine development and to processing and presentation of viral epitopes.

Amino Acid Sequence↗
PubMed1991

Cationization of protein antigens. VI. Effects of cationization on the immunoregulatory properties of a bovine serum albumin peptide, a.a. 506-589.

Cationization of bovine serum albumin (BSA) causes a profound increase in its immunogenicity. To establish if immunoregulatory properties of an immunosuppressive peptide are affected by cationization, a BSA peptide, a.a. 506-583, was cationized and tested for its immunogenic properties. A greatly reduced amount of cationized peptide compared to native peptide was required to stimulate BSA-primed T cells to proliferate in vitro. Mice primed with the cationized peptide administered with an adjuvant responded with a significantly greater anti-BSA response than mice immunized with the native form of the peptide. In the absence of an adjuvant i.v. or i.p. administration of the native peptide was immunosuppressive, while the cationized form was immunoenhancing. Both forms of the peptide stimulated in vivo induction of L3T4+ (CD4), and Lyt-2+ (CD8) T cells. Removal of Lyt-2+ T cells from lymph node cultures following immunization with the native peptide caused a significant increase in the proliferation of the remaining T cells. This increase was not observed when the mice were immunized with the cationized peptide. No major BSA B cell determinants were present within the peptide sequence. Mice immunized with the peptide exhibited a negligible anti-BSA antibody response compared to those immunized with the whole BSA molecule. Furthermore, the peptide did not inhibit anti-BSA antibody binding to BSA. We demonstrated that cationization modifies immunoregulatory properties of an immunosuppressive BSA-derived peptide.

Animals↗