The hairless rat (WBN/Kob-Ht), a dominant mutant rat derived from the Wistar strain, rarely develops spontaneous erythema of a progressive nature on its skin. Erythema was first observed at 8 weeks of age and the incidence at 20 weeks of age was about 4% in both males and females. Histopathologically, erythema was characterised by dermatitis induced by an immunological reaction. Areas of erythema in the skin were decreased by treatment with dexamethasone (1 mg/kg) or ciclosporin (25 or 50 mg/kg). These results suggested that erythema on the hairless rat could be used as an animal model of spontaneous dermatitis. (+info)
(2/527) Correction of bone marrow failure in dyskeratosis congenita by bone marrow transplantation.
Dyskeratosis congenita is recognized by its dermal lesions and constitutional aplastic anemia in some cases. We report successful allogeneic bone marrow transplantation in two siblings with this disease from their sister, and their long term follow-up. We used reduced doses of cyclophosphamide and busulfan for conditioning instead of total body irradiation. Also, we report late adverse effects of transplantation which are not distinguishable from the natural course of disease. (+info)
(3/527) The UV waveband dependencies in mice differ for the suppression of contact hypersensitivity, delayed-type hypersensitivity and cis-urocanic acid formation.
Solar radiation contains ultraviolet B (280-315 nm) and ultraviolet A (ultraviolet AII, 315-340 nm; ultraviolet AI, 340-400 nm) wavebands. Ultraviolet B is known to suppress certain aspects of cell mediated immunity. Using three ultraviolet lamps (the broad-band ultraviolet B TL-12, the narrow-band ultraviolet B TL-01 and an ultraviolet AI source), we investigated the dose and waveband dependencies for the suppression of contact hypersensitivity to oxazolone and delayed-type hypersensitivity to herpes simplex virus, plus the formation of cis-urocanic acid in C3H/HeN mice. A single exposure of 1500 J/m2 TL-12 or 10,000 J/m2 TL-01 or 500,000 J/m2 ultraviolet AI corresponded to 1 minimum erythema dose in this mouse strain. The percentage of cis-urocanic acid of the total urocanic acid rose from a background level of 1.7% to 40% with 1000 J/m2 TL-12 or 10,000 J/m2 TL-01, but only 17% cis-urocanic acid was obtained with 500,000 J/m2 ultraviolet AI. The contact hypersensitivity response was significantly suppressed after a minimum dose of 5000 J/m2 TL-12 or 50,000 J/m2 TL-01 or 500,000 J/m2 ultraviolet AI. The delayed-type hypersensitivity response was suppressed by a minimum dose of 100 J/m2 TL-12 or 10,000 J/m2 TL-01 or 1000 J/m2 ultraviolet AI. So, whereas a low dose of ultraviolet AI reduced the delayed-type hypersensitivity response, a 500-fold higher dose was required to suppress contact hypersensitivity. There was no correlation between the suppression of these responses and the concentration of cis-urocanic acid in the skin. Thus different mediators may modulate the various immune responses affected by ultraviolet exposure, depending on the wavelength of the radiation. (+info)
(4/527) Comparison of in vitro and in vivo human skin responses to consumer products and ingredients with a range of irritancy potential.
Human skin equivalent cultures were investigated as possible pre-clinical skin irritation screens to aid safety assessments for chemicals and product formulations, and to facilitate design of safe and efficient human studies. In vitro responses in human skin equivalent cultures were compared directly to in vivo human skin responses from historic or concurrent skin tests for representative chemicals and products, including surfactants, cosmetics, antiperspirants, and deodorants. The in vivo data consisted of visual scores (i.e., erythema and edema) from skin-patch tests and diary accounts of skin irritation from product-use studies. In the in vitro studies, cornified, air-interfaced human skin cultures (EpiDerm) were evaluated using methods designed to parallel human clinical protocols with topical dosing of neat or diluted test substances to the stratum corneum surface of the skin cultures. The in vitro endpoints have previously been shown to be relevant to human skin irritation in vivo, including the MTT metabolism assay of cell viability, enzyme release (lactate dehydrogenase and aspartate aminotransferase), and inflammatory cytokine expression (Interleukin-1alpha). For surfactants, dose-response curves of MTT cell-viability data clearly distinguished strongly-irritating from milder surfactants and rank-ordered irritancy potential in a manner similar to repeat-application (3x), patch-test results. For the antiperspirant and deodorant products, all the in vitro endpoints correlated well with consumer-reported irritation (r, 0.75-0.94), with Interleukin-1alpha (IL-1alpha) release, showing the greatest capacity to distinguish irritancy over a broad range. IL-1alpha release also showed the best prediction of human skin scores from 14-day cumulative irritancy tests of cosmetic products. These results confirm the potential value of cornified human skin cultures as in vitro pre-clinical screens for prediction of human skin irritation responses. A preliminary report of these results has been published. (+info)
(5/527) Low-dose UVA and UVB have different time courses for suppression of contact hypersensitivity to a recall antigen in humans.
This study investigates the relative effects of low-dose solar-simulated ultraviolet, ultraviolet A, and ultraviolet B radiation on the elicitation of contact hypersensitivity to nickel in nickel-allergic volunteers. A xenon arc lamp with changeable filters was used to irradiate groups of volunteers daily, on separate areas of their lower backs, with both solar-simulated ultraviolet (ultraviolet B, ultraviolet AII + ultraviolet AI) and ultraviolet A (same ultraviolet AII content but twice the ultraviolet AI as the solar-simulated ultraviolet spectrum) for 1 and 2 d; 3, 4, and 5 d; and from 1 to 4 wk. A fourth group was irradiated for 1-5 d with the ultraviolet B component of solar-simulated ultraviolet. Following the final irradiation in each group, nickel-containing patches were applied to both ultraviolet-treated sites and adjacent, unirradiated control sites. Erythema caused by nickel contact hypersensitivity at each site was quantitated 72 h later with a reflectance erythema meter. By comparing the nickel reactions of irradiated and unirradiated skin, ultraviolet immunosuppression was assessed with the different spectra and durations of ultraviolet exposure. We found significant immunosuppression with daily doses of ultraviolet B and ultraviolet A equivalent to approximately 6 min of summer sun exposure, and that ultraviolet A and ultraviolet B exerted their maximal immunosuppressive effects at different times. Solar-simulated ultraviolet-induced immunosuppression was significant after one exposure, near-maximal after two exposures and remained elevated thereafter. Ultraviolet B-induced immunosuppression was lower than that induced by solar-simulated ultraviolet, but followed a similar time-course. In contrast, ultraviolet A-induced immunosuppression was transient, peaking after three exposures. Immune responses returned towards normal with subsequent ultraviolet A exposure, suggesting that an adaptive mechanism may prevent immunosuppression by continued ultraviolet A irradiation. (+info)
(6/527) Interferon-gamma is involved in photoimmunoprotection by UVA (320-400 nm) radiation in mice.
Ultraviolet B radiation not only inflicts tumor-initiating DNA damage, but also impairs T cell-mediated immunity relevant to survival of the initiated cells. We have reported, however, that ultraviolet A radiation, in contrast, is immunologically innocuous in hairless mice and opossums, but renders the animals resistant to the immunosuppression by ultraviolet B, or its mediator cis-urocanic acid. Ultraviolet B irradiation of skin causes abundant release of numerous cytokines (interleukin-1, interleukin-6, interleukin-10, tumor necrosis factor-alpha); notably interleukin-12 and interferon-gamma do not appear to be upregulated. A recent report has indicated that interleukin-12 protects from photoimmunosuppression in mice, but it remains unclear whether interleukin-12 acts directly or via interferon-gamma, which it is known to stimulate. Here we investigate the possible role of interferon-gamma in UVA photoimmunoprotection, using interferon-gamma gene knockout mice in comparison with control C57/BL6 mice, and the systemic contact hypersensitivity reaction (induced by sensitization through a nonirradiated skin site) to measure immunity. interferon-gamma-/- mice raised normal contact hypersensitivity responses, and were unaffected, as were C57BL control mice, by ultraviolet A exposure. In response to ultraviolet B irradiation or topical cis-urocanic acid treatment, control mice became immunosuppressed by 69% and 27%, respectively, and interferon-gamma-/- mice by 79% and 27%. When ultraviolet B exposure or cis-urocanic acid was followed by ultraviolet A irradiation, however, contact hypersensitivity was totally restored in control mice, but remained suppressed by 55% and 25%, respectively, in interferon-gamma-/- mice. Injection of recombinant interferon-gamma in the interferon-gamma-/- mice restored the ultraviolet A protective effect against cis-urocanic acid-induced immunosuppression. These observations suggest that interferon-gamma plays a part in ultraviolet A immunoprotection from the suppressive effect of ultraviolet B radiation and, and that the mechanism appears to be via antagonism by this cytokine of the cis-urocanic acid immunosuppressive action. (+info)
(7/527) Acute systemic reaction and lung alterations induced by an antiplatelet integrin gpIIb/IIIa antibody in mice.
Shock is frequently accompanied by thrombocytopenia. To investigate the pathogenic role of platelets in shock, we examined the in vivo effects of monoclonal antibodies (MoAbs) against mouse platelet membrane proteins. Injection of the platelet-specific MoAb MWReg30 to the fibrinogen receptor (gpIIb/IIIa) rendered mice severely hypothermic within minutes. Isotype-matched control antibodies, even if they also recognized platelet surface antigens, did not induce comparable signs. MWReg30 induced early signs of acute lung injury with increased cellularity in the lung interstitium and rapid engorgement of alveolar septal vessels. Despite this in vivo activity, MWReg30 inhibited rather than stimulated platelet aggregation in vitro. MWReg30-binding to platelets led to phosphorylation of gpIIIa, but did not induce morphological signs of platelet activation. The MWReg30-induced reaction was abolished after treatment with MoAbs 2.4G2 to FcgammaRII/III and was absent in FcgammaRIII-deficient mice, clearly demonstrating the requirement for FcgammaRIII on involved leukocytes. Simultaneous administration of tumor necrosis factor exacerbated, whereas a tolerizing regimen of tumor necrosis factor or bacterial lipopolysaccharide completely prevented the reaction. These data suggest that platelet surface-deposited MWReg30-immune complexes lead to an acute Fc-mediated reaction with pulmonary congestion and life-threatening potential that could serve as an in vivo model of acute lung injury. (+info)
(8/527) Comparison study of combined DTPw-HB vaccines and separate administration of DTPw and HB vaccines in Thai children.
The safety, immunogenicity and tolerability of two different DTPw-HBV combination vaccines, containing 5 and 10 microg of HBsAg; were investigated in comparison with separate administration of DTPw and HBV (10 microg of HBsAg). A three dose primary vaccination course at 2, 4 and 6 months of age was followed by a booster dose at 18 months. All vaccines were safe and well tolerated. The DTPw-HBV combination vaccine containing 10 microg of HBsAg elicited significantly higher anti-HBs titres than the other two vaccines after the primary and booster vaccination course. All vaccines elicited a high response against the other components. Based on these results, DTPw-HBV (10 microg HBsAg) was the most effective vaccine at this schedule. (+info)