C57BL/6 mice were orally immunized with five weekly doses of 2 mg, 200 μg, or 2 μg of Helicobacter pylori (Sydney strain) whole-cell sonicate combined with cholera toxin. One week after the last vaccination, mice were challenged with 5 × 107CFU of live H. pylori three times at 2-day intervals. At 6 or 18 weeks after the challenge, mice were sacrificed and bacterial cultures and histological studies of the stomach were performed. Vaccination with 2 mg/session or 200 μg/session inhibited H. pylori colonization by 90 and 100%, respectively. These mice were considered protected. Lower levels of H. pylori-specific immunoglobulin A (IgA) were detected in fecal and saliva samples before challenge. However, a significant increase in IgA secretion in mucosal tissue and a higher labeling index for IgA-positive lumina of pyloric glands were noted in these mice in response to challenge and in a vaccine dose-dependent manner. In protected mice, however, severe gastritis characterized by marked infiltration of inflammation mononuclear cells was noted at 6 weeks after challenge, compared with the gastritis seen in unprotected mice or nonvaccinated, ordinarily infected mice. Marked expression of gamma interferon mRNA was detected in the stomach of all protected mice, and 50% of these mice expressed interleukin 4 (IL-4) or IL-5 mRNA. Our findings suggest that local secretory IgA antibody and severe postimmunization gastritis correlate well with protection of mice against H. pylori infection.
We examined the efficacy of therapeutic oral vaccination using Helicobacter pylori-whole cell sonicate and cholera toxin (CT) in mice persistently infected with H. pylori. Efficacy was determined by bacterial culture and microscopic examination of gastric tissues for the persistence of bacteria at 6 weeks after the last vaccination. Vaccination of H. pylori-whole cell sonicate combined with CT eradicated bacteria in 10/16 mice (62.5%). Interestingly, oral vaccination with CT alone also eliminated the bacteria in 8/17 mice (47.1%). However, a therapeutic intraperitoneally administered vaccine failed to eradicate H. pylori from the stomach (1/17 mice, 5.9%). Identification of the type of immunity involved in the eradication process showed that oral vaccination enhanced the antigen-specific IgA in the feces and saliva. The efficacy of eradication of H. pylori correlated well with increases in IgA secretion in mucosal tissue and a higher labeling index of IgA-positive lumina of pyloric glands. Moreover, the expression of IL-4 mRNA in the stomach of mice with eradicated bacteria was higher than in the uneradicated group. Our results suggest that the efficacy of vaccination depends on the mucosal IgA response in the gastrointestinal tract against H. pylori via Th2 cell activation and that therapeutic oral vaccination induces a mucosal immune response sufficient to eradicate long-term infection with H. pylori.
To determine the relationship between visual acuity and three-dimensional optical coherence tomographic (3D-OCT) findings of the macula in eyes with Vogt-Koyanagi-Harada (VKH) disease. Twelve eyes of six patients (three men and three woman, average age 53.2 years) in the acute phase of VKH disease were examined with a 3D-OCT instrument. All of the eyes had a serous macular detachment. The height of the sensory retinal detachment (SRD) and the sensory retinal thickness (SRT) were measured by OCT before treatment (acute stage) and at the convalescent stage. The correlation between the retinal morphology and visual acuity was evaluated. The height of the SRD and the SRT were 612.5 ± 371.2 and 136. 7 ± 22.0 μm, respectively. The initial visual acuity was significantly worse in eyes with a higher SRD (P = 0.014, r = 0.68) but the correlation between initial visual acuity and SRT was not significant. The recovery of visual acuity was attained in 50.7 ± 44.1 days and the complete resolution of the SRD was attained in 30.5 ± 23.2 days. The final visual acuity was attained several days after the complete resolution of the SRD in all four eyes of patients over 60 years of age, but the recovery of visual acuity often preceded the complete resolution of the SRD. The OCT images provided a noninvasive indicator of the severity of the disease and dynamic changes in the macular morphology, reflecting the effect of treatment in association with the improvement in visual acuity. Monitoring the SRD by 3D-OCT may guide the tapering of systemic corticosteroid treatment.
Background: Endogenous endophthalmitis is a rare disease and its visual prognosis is poor. Case Reports: We present two patients, a 60-year-old man and a 53-year-old man, who developed endogenous endophthalmitis caused byGram-positive organismsbut recovered good vision after antibiotics and vitrectomy. Results: The first patient complained of ocular pain and visual decrease in his right eye. Ophthalmoscopy showed inflammation in the anterior chamber and vitreous opacities. Antibiotic was administrated systemically, and blood culture detected Streptococcus anginosus. He underwent successful heart surgery for endocarditis and total dental extraction for severe gingivitis. Vitrectomy was performed 36 days after the onset and vision improved from 0.02 to 0.7. The second patient was referred for acute visual decrease in his left eye. Severe iritis and vitreous opacities were observed, and systemic examination showed acute pyelitis and prostatic abscesses. Blood cultures detected Staphylococcus sp., and systemic antibiotics were given. Vitrectomy was performed 12 days after the onset, and vision improved from 0.06 to 1.2. Conclusions: We conclude that the rapid treatment with systemic antibiotics for the organisms at the primary site, and the vitrectomy, even though delayed, can lead to a good recovery of vision.
A 71-year-old woman and her elder sister developed ligneous conjunctivitis after ocular surgery. Laboratory tests demonstrated that the proband and her sister had 6.6% and 8.1% of plasminogen activity, and 1.2 and 1.4 mg/dl of antigen, respectively. Thus, they were diagnosed as having severe type I plasminogen deficiency, for the first time, in Japan. DNA sequencing and PCR-RFLP analyses revealed that these two cases are homozygotes of a novel A-to-G mutation at the obligatory splicing acceptor site in intron-C. Both cases were satisfactorily treated with a direct thrombin inhibitor, topical Argatroban, and topical plasma obtained from their healthy family members. Am. J. Hematol. 84:363-365, 2009. V
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