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Biomedical subjects

J B Sun

Publications and source records attributed to J B Sun.

At least 19 recordsLinked to original sources
PubMed2006

Sensitive electrochemical enzyme immunoassay microdevice based on architecture of dual ring electrodes with a sensing cavity chamber.

A novel electrochemical detection architecture was investigated for enzyme immunoassay sensors. Microchips with dual-ring working and counter electrodes, and a sensing cavity chamber were made on glass slides. The glass surface of the microchip was coated by 3-aminopropyltriethoxysilane (APTES). Goat IgG, as a example, was covalently captured on APTES-modified glass surfaces through glutaraldehyde (GA) as a cross-linker. Enzyme substrate, p-aminophenyl phosphate (PAPP) was prepared by electrolysis. The enzyme conversion from home-synthetic PAPP to p-aminophenol (PAP) was examined by differential pulse voltammetry (DPV). A competitive inhibition enzyme-linked immunosorbant assay (ELISA) was designed to test the system. Experimental results demonstrate that a detection limit of 118 fg/ml of goat IgG and a dynamic range of 118 fg/ml to 1.18 ng/ml, up to five orders of magnitude could be achieved. Due to its novel architecture design and electronic detection scheme, the method can be used to fabricate portable electrochemical ELISA lab-on-chip systems. The technology could have great potential in clinical diagnostic applications.

Animals↗
PubMed2001

Nasal administration of Schistosoma mansoni egg antigen-cholera B subunit conjugate suppresses hepatic granuloma formation and reduces mortality in S. mansoni-infected mice.

Granulomatous inflammation in schistosomiasis is a delayed-type hypersensitivity reaction mediated by CD4+ T cells specific for parasite egg antigens (Ags). In an attempt to control T-cell responses leading to excessive harmful inflammation and granuloma formation, especially in the liver, BALB/c mice were intranasally (i.n.) treated with soluble Schistosoma mansoni egg Ags (SEA) conjugated to cholera toxin B subunit (CTB), a mucosa-binding protein with demonstrated capacity to suppress inflammatory T-cell functions after mucosal administration. Treatment with CTB-SEA significantly conjugate a reduced liver granuloma formation in infected mice associated with decreased SEA specific Th1- and Th2-type immune responses by liver leukocytes. Importantly, treatment with CTB-SEA conjugate also significantly reduced the mortality in chronically infected mice. In S. mansoni-infected large-granuloma forming CBA mice, i.n. treatment with purified Sm-p40, the major egg antigen, conjugated to CTB likewise significantly inhibited hepatic egg granuloma formation. A reduction of SEA-driven lymphoproliferation and of interferon (IFN)-gamma, interleukin (IL)-4 and IL-5 production, together with an increase in transforming growth factor (TGF)-beta1 production, were observed in splenic cells from CTB-Sm-p40-treated SEA-sensitized mice, as well as in liver leukocytes from CTB-Sm-p40-treated schistosome-infected mice. These results indicate that mucosal administration of SEA or purified Sm-p40 antigen in conjunction with CTB is highly effective in curtailing immunopathologic manifestations of schistosomiasis in vivo in infected hosts.

Administration, Intranasal↗
PubMed2000

Enhanced immunological tolerance against allograft rejection by oral administration of allogeneic antigen linked to cholera toxin B subunit.

A single oral intragastric administration of cholera toxin B subunit (CTB) conjugated to allogeneic thymocytes (ATC, 4 x 10(7) cells) under conditions allowing the CTB to bind the complex to GM1 ganglioside receptors was shown to be efficacious in inducing peripheral T cell tolerance associated with significant suppression of both primary and secondary accelerated rejection of heart allografts when tested in mice. Allogeneic in vivo delayed-type hypersensitivity (DTH), in vitro cytotoxicity responses, and mixed lymphocyte reactions (MLR) by T cells from mesenteric lymph nodes (MLN), popliteal lymph nodes (PLN), and spleen were significantly reduced in mice treated with the CTB-ATC conjugate, as were also the numbers of cells in these organs producing IL-2, IFN-gamma, or IL-4. In contrast, a marked increase in the production of IL-4 in Peyer's patches (PP) and of TGF-beta(1) in PLN was observed. The suppressive potential of T cells from PP and/or MLN after oral treatment with CTB-ATC was further evident by intraperitoneal transfer of such cells from CTB-ATC-treated animals to primed recipients, which led to marked suppression of both allogen-specific DTH and MLR responses. A critical role for PP in inducing peripheral tolerance after oral CTB-ATC treatment was indicated by the absence of tolerance induction in animals whose PP had been destroyed before treatment with CTB-ATC. The results indicate that the protection against allograft rejection by oral treatment with CTB-ATC is mediated by T cells and associated with a strong induction of IL-4 production at mucosal sites and TGF-beta(1) at the effector sites.

Adjuvants, Immunologic↗
PubMed2000

Prolonged oral treatment with low doses of allergen conjugated to cholera toxin B subunit suppresses immunoglobulin E antibody responses in sensitized mice.

BACKGROUND: Oral tolerance is a long recognized method for inducing systemic immunological tolerance. However, large doses of antigen and frequent administrations are often required. By linking the antigen to the nontoxic mucosa-binding B subunit of cholera toxin (CTB), the required amount can be dramatically reduced. We have previously shown that mucosal administration of small amounts of antigens coupled to CTB can suppress peripheral Th1 cell-reactivity and associated inflammatory immunopathology in both naive and systemically-immunized animals. Induction of oral tolerance by repeated feeding of relatively small doses of antigen has, in some cases been shown to involve the generation of regulatory Th2-like CD4+ T cells, and hence could promote rather than suppress type I immunoglobulin (Ig) E-mediated allergic responses. OBJECTIVES: We examined whether oral prophylactic or therapeutic administration of a model allergen coupled to CTB would modulate allergen-specific IgE responses in high IgE responder Balb/c mice. METHODS: Ovalbumin (OVA) was used as a model allergen. Mice were treated perorally with free or CTB-coupled OVA before or after systemic priming with alum-adsorbed OVA. Allergen-specific IgE levels in serum were measured with the passive cutaneous anaphylaxis test at various time-points. RESULTS: Oral administration of a single low dose of CTB-linked OVA, prior to systemic sensitization and challenge with OVA, suppressed allergen-specific serum IgE antibody responses. Treatment with comparable doses of free OVA was much less effective. Most importantly, oral treatment with CTB-OVA conjugate could also suppress an already initiated IgE antibody response, but to achieve such a 'therapeutic effect', administration of multiple low doses of conjugate over a long time was required. Oral treatment with CTB-OVA conjugate could also effectively suppress antigen-specific Th1-mediated delayed-type hypersensitivity. Thus treatment with a CTB-conjugated model allergen can affect a broad range of T-cell-driven immune responses, even in antigen-experienced animals. CONCLUSION: These results may impact on the development of therapeutic vaccines against type I allergies.

Administration, Oral↗
PubMed2000

Oral administration of cholera toxin B subunit conjugated to myelin basic protein protects against experimental autoimmune encephalomyelitis by inducing transforming growth factor-beta-secreting cells and suppressing chemokine expression.

The efficacy and mechanism of immunosuppression against experimental autoimmune encephalomyelitis (EAE) by oral low-dose administration of myelin basic protein (MBP) conjugated to cholera toxin B subunit (CTB) were investigated in Lewis rats immunized with MBP together with complete Freund's adjuvant 4 days before the start of treatment. Oral treatment with CTB-MBP conjugate gave almost complete protection against disease, an effect that was totally abrogated by including a low dose of cholera holotoxin (CT). The protection by CTB-MBP was associated with a dramatic reduction in the number of leukocytes staining for CD4, CD8, IL-2R or MHC class II in the spinal cord as examined by immunohistochemistry. The mRNA expressions of T(h)1 cytokines IFN-gamma, IL-12 and tumor necrosis factor-alpha, as well as of chemokines monocyte chemotactic protein (MCP)-1 and RANTES in the spinal cord were also reduced by 76-94%, as assessed by in situ hybridization. In contrast, transforming growth factor (TGF)-beta mRNA-expressing cells were strongly increased in the spinal cord from animals treated orally with the CTB-MBP conjugate. In the draining peripheral lymph nodes, the number of MBP-specific TGF-beta mRNA-expressing cells was also increased, whereas there was a decrease in cells expressing T(h)1 or T(h)2 cytokine mRNA. Protection against EAE could be transferred by injection of cells from the mesenteric lymph nodes of animals fed with CTB-MBP into naive animals exposed to encephalitogenic T cells. The results indicate that the protective anti-inflammatory effect by oral treatment with CTB-MBP conjugate is, to a large extent, due to the induction of TGF-beta-secreting suppressive-regulatory T cells and to local down-regulation of MCP-1 and RANTES in the spinal cord.

Administration, Oral↗
PubMed2000

[A study of low temperature catalyst for Sabatier reaction].

Objective. To develop a low temperature catalyst for the Sabatier CO2 reduction of the atmospheric regeneration system and lower the start-up temperature of the Sabatier reaction. Method. A low temperature catalyst was designed from the considerations of the active composition, the choice of the carrier, the production method and condition of the catalyst. Then the performance of the newly developed low temperature catalyst was tested. Result. A new low temperature catalyst for the Sabatier reaction using Ru as the active composition and using r-Al2O3 as the carrier was developed. The start-up temperature was lower than 110 degrees C and the start-up time was 8 min; The conversion efficiency of the lean component (H2 or CO2) was over 95 percent when the temperature of the reactor was from 200 degrees C to 300 degrees C; The reaction product water was nearly colorless, transparent and neutral. Conclusion. The test results showed that the goals of the design are achieved and it is worthwhile to make further studies on the low temperature catalyst.

Air Conditioning↗
PubMed1999

Intranasal administration of a Schistosoma mansoni glutathione S-transferase-cholera toxoid conjugate vaccine evokes antiparasitic and antipathological immunity in mice.

Mucosal administration of Ags linked to cholera toxin B subunit (CTB) can induce both strong mucosal secretory IgA immune responses and peripheral T cell hyporeactivity. In this study, intranasal (i.n. ) administration of CTB-conjugated Schistosoma mansoni 28-kDa GST (CTB-Sm28GST) was found to protect infected animals from schistosomiasis, especially from immunopathological complications associated with chronic inflammation. Worm burden and liver egg counts were reduced in infected animals treated with the CTB-Sm28GST conjugate as compared with mice infected only, or with mice treated with a control (CTB-OVA) conjugate. However, a more striking and consistent effect was that granuloma formations in liver and lungs of mice treated with CTB-Sm28GST were markedly suppressed. Such treatment was associated with reduced systemic delayed-type hypersensitivity and lymphocyte proliferative responses to Sm28GST. Production of IFN-gamma, IL-3, and IL-5 by liver cells was also markedly reduced after i.n. treatment of CTB-Sm28GST, whereas IL-4 production was not impaired. Intranasal treatment of infected mice with CTB-Sm28GST increased IgG1-, IgG2a-, IgA-, and IgE-Ab-forming cell responses in liver in comparison with treatment with CTB-OVA, or free Sm28GST. Most importantly, mucosal treatment with CTB-Sm28GST significantly reduced animal mortality when administered to chronically infected mice. Our results suggest that it may be possible to design a therapeutic vaccine against schistosomiasis that both limits infection and suppresses parasite-induced pathology.

Administration, Intranasal↗
PubMed1999

Treatment of experimental autoimmune arthritis by nasal administration of a type II collagen-cholera toxoid conjugate vaccine.

OBJECTIVE: To assess the efficacy of intranasal administration of microgram amounts of type II collagen (CII) coupled to cholera toxin B subunit (CTB) with respect to the development of collagen-induced arthritis, even when given after the onset of clinically evident arthropathy. METHODS: DBA/1 mice were immunized with CII to induce arthritis and were subsequently treated with CTB-CII, CTB-conjugated ovalbumin, or CII alone. The incidence and severity of arthritis were assessed clinically and histologically. RESULTS: Treatment with CTB-CII conjugate effectively suppressed leukocyte infiltration into the synovium and prevented bone erosion. Comparable doses of unconjugated CII administered by the same route were relatively ineffective. Protection with nasal CTB-CII vaccine was associated with decreased production of interleukin-4 (IL-4), IL-6, and interferon-gamma and with reduced CII-specific IgG1 and IgG2a antibody responses in regional lymph nodes. CONCLUSION: Nasal treatment with CTB-CII appears to result in decreased peripheral Th1 and Th2 responses to collagen. These results suggest that intranasal vaccination with CTB-CII may offer an effective immunotherapeutic means for the control of chronic polyarthritis.

Administration, Intranasal↗
PubMed1999

Mucosal immunity and tolerance: relevance to vaccine development.

The mucosal immune system of mammals consists of an integrated network of lymphoid cells which work in concert with innate host factors to promote host defense. Major mucosal effector immune mechanisms include secretory antibodies, largely of immunoglobulin A (IgA) isotype, cytotoxic T cells, as well as cytokines, chemokines and their receptors. Immunologic unresponsiveness (tolerance) is a key feature of the mucosal immune system, and deliberate vaccination or natural immunization by a mucosal route can effectively induce immune suppression. The diverse compartments located in the aerodigestive and genitourinary tracts and exocrine glands communicate via preferential homing of lymphocytes and antigen-presenting cells. Mucosal administration of antigens may result in the concomitant expression of secretory immunoglobulin A (S-IgA) antibody responses in various mucosal tissues and secretions, and under certain conditions, in the suppression of immune responses. Thus, developing formulations based on efficient delivery of selected antigens/tolerogens, cytokines and adjuvants may impact on the design of future vaccines and of specific immunotherapeutic approaches against diseases associated with untoward immune responses, such as autoimmune disorders, allergic reactions, and tissue-damaging inflammatory reactions triggered by persistent microorganisms.

Adjuvants, Immunologic↗
PubMed1999

[The present status and development of thermal control system of spacesuits for extravehicular activity].

With the extension of extravehicular activity (EVA) duration, the need for more effective thermal control of EVA spacesuits is required. The specific schemes investigated in heat sink system for EVA are discussed, including radiator, ice storage, metal hydride heat pump, phase-change storage/radiator and sublimator. The importance and requirements of automatic thermal control for EVA are also discussed. Existed automatic thermal control for EVA are reviewed. Prospects of further developments of thermal control of spacesuits for EVA are proposed.

Astronauts↗
PubMed1999

[Safety analysis for astronaut and the personal protective equipment].

Objective. To analyze and study astronaut and his personal equipment safety. Method. Three of the most widely used approaches, failure mode and effect analysis (FMEA), fault tree analysis (FTA) and system hazards analysis (SHA) were used. Result. It was demonstrated that astronaut and the personal equipment are subjected to various potential hazards, such as human errors, astronaut illness, fire or space suit emergency decompression, etc. Their causes, mechanisms, possible effects and criticality of some critical potential hazards were analyzed and identified in more details with considerations of the historic accidents of manned spaceflight. And the compensating provisions and preventive measures for each hazard were discussed. Conclusion. The analysis study may be helpful in enhancing the safety of the astronaut and its personal protective equipment.

Accident Prevention↗
PubMed1996

Treatment of experimental autoimmune encephalomyelitis by feeding myelin basic protein conjugated to cholera toxin B subunit.

Oral administration of autoantigens can prevent and partially suppress autoimmune diseases in a number of experimental models, Depending on the dose of antigen fed, this approach appears to involve distinct yet reversible and short-lasting mechanisms (anergy/deletion and suppression) and usually requires repeated feeding of large (suppression) to massive (anergy/deletion) amounts of autoantigens to be effective. Most importantly, this approach is relatively less effective in animals already systemically sensitized to the fed antigen, such as in animals already harboring autoreactive T cells and, thus, presumably also in humans suffering from an autoimmune disorder. We have previously shown that feeding a single dose of minute amounts of antigens conjugated to cholera toxin B subunit (CTB) can effectively suppress delayed-type hypersensitivity reactions in systemically immune animals. We now report that feeding small amounts of myelin basic protein (MBP) conjugated to CTB either before or after disease induction protected rats from experimental autoimmune encephalomyelitis. Such treatment was as effective in suppressing interleukin 2 production and proliferative responses of lymph node cells to MBP as treatment involving repeated feeding with much larger (50- to 100-fold) doses of free MBP. Different from the latter treatment, which led to decreased production of interferon-gamma in lymph nodes, low-dose oral CTB-MBP treatment was associated with increased interferon-gamma production. Most importantly, low-dose oral CTB-MBP treatment greatly reduced the level of leukocyte infiltration into spinal cord tissue compared with treatment with repeated feeding of large doses of MBP. These results suggest that the protection from experimental autoimmune encephalomyelitis achieved by feeding CTB-conjugated myelin autoantigen involves immunomodulating mechanisms that are distinct from those implicated by conventional protocols of oral tolerance induction.

Animals↗
PubMed1995

Lyme neuroborreliosis: evidence for persistent up-regulation of Borrelia burgdorferi-reactive cells secreting interferon-gamma.

The T-cell response to the aetiologic pathogen Borrelia (B.) burgdorferi in patients with Lyme neuroborreliosis (LN) and in control patients with other neurological diseases was examined by enumerating B. burgdorferi-reactive T cells secreting interferon-gamma (IFN-gamma) with an ELIspot assay. LN patients had elevated numbers of B. burgdorferi-reactive IFN-gamma secreting cells in blood and approximately 20-fold enriched in the cerebrospinal fluid (CSF). A positive correlation existed in CSF between B. burgdorferi-reactive IFN-gamma secreting cells and B cells secreting anti-B. burgdorferi IgG antibodies. The up-regulation of antigen-specific IFN-gamma secreting cells persisted in peripheral blood up to at least 9 months and in the CSF for at least 4 months after termination of treatment with antibiotics, when the patients were mostly free from clinical signs and symptoms due to LN. How IFN-gamma interplays with other cytokines and influences the pathogenesis of LN remains to be studied.

Adult↗