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Chronic periodontitis is associated with Porphyromonas gingivalis infection. Although virulence factors of P. gingivalis are hypothesized to contribute to the pathogenesis of periodontitis, it is unclear whether the local CD4(+) T-cell-mediated response they elicit prevents or contributes to periodontal bone destruction. We hypothesize that major histocompatibility complex class II I-A(b) -binding peptides existing in Kgp and RgpA are presented to CD4(+) T cells during P. gingivalis oral colonization. The protein sequences of gingipains RgpA and Kgp, and OMP40 and OMP41 of P. gingivalis were scanned using an I-A(b) -binding matrix. From this analysis we identified 53 candidate peptides that had the potential to engage the peptide-binding groove of the I-A(b) molecule of C57BL/6 mice. An ELISpot-based screen revealed those peptide-primed effector/memory CD4(+) T cells that could be re-stimulated in vitro with P. gingivalis or the peptide itself to produce interleukin-17A or interferon-γ. Two immunodominant peptides, Kgp467-477 (pKgp) and RgpA1054-1064 /Kgp1074-1084 (pR/Kgp) were identified and engineered to be displayed on I-A(b) molecular tetramers. Peptide pR/Kgp is conserved across all sequenced P. gingivalis strains. C57BL/6 mice were orally inoculated with P. gingivalis strain 53977 and cervical lymph node cells were stained with phycoerythrin-conjugated pKgp::I-A(b) and pR/Kgp::I-A(b) tetramers. We found that only pR/Kgp::I-A(b) bound with the desired specificity to gingipain-specific CD4(+) T cells. The pR/Kgp::I-A(b) tetramer complex will allow the identification of effector/memory CD4(+) T cells specific for two virulence factors of P. gingivalis strains associated with periodontal disease.

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BACKGROUND: Hydroxyisohexyl 3-cyclohexene carboxaldehyde (HICC) is a synthetic fragrance ingredient. Case reports of allergy to HICC appeared in the 1980s, and HICC has recently been included in the European baseline series. Human elicitation dose-response studies performed with different allergens have shown a significant relationship between the patch-test threshold and the repeated open application test (ROAT) threshold, which mimics some real-life exposure situations. Fragrance ingredients are special as significant amounts of allergen may evaporate from the skin. OBJECTIVES: The study aimed to investigate the relationship between elicitation threshold doses at the patch test and the ROAT, using HICC as the allergen. The expected evaporation rate was calculated. MATERIALS AND METHODS: Seventeen HICC-allergic persons were tested with a dilution series of HICC in a patch test and a ROAT (duration up to 21 days). Seventeen persons with no HICC allergy were included as control group for the ROAT. Results The response frequency to the ROAT (in microg HICC cm(-2) per application) was significantly higher than the response frequency to the patch test at one of the tested doses. Furthermore the response rate to the accumulated ROAT dose was significantly lower at half of the doses compared with the patch test. The evaporation rate of HICC was calculated to be 72% over a 24-h period. CONCLUSIONS: The ROAT threshold in dose per area per application is lower than the patch test threshold; furthermore the accumulated ROAT threshold is higher than the patch test threshold, which can probably be explained by the evaporation of HICC from the skin in the open test.

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Commensal microorganisms colonize the nasal mucosa without inducing inflammation. Pathogens perturbing the commensal flora often invade evading immune defenses. The different types of adaptive responses that drive the distinct behaviors of commensals and pathogens, allowing one to persist at mucosal surfaces and the other to survive within tissues, are not yet clear. In the present work we demonstrate that although crossing epithelial barriers, the commensal Lactobacillus murinus stimulates epitope-specific CD4(+) T cells in nasal-associated lymphoid tissue (NALT) less efficiently than the pathogen Streptococcus pyogenes. In NALT antigen-presenting cells other than CCR6(+) CD11c(+) dendritic cells process and present the microbial antigens. Effector/memory CD4(+) T cells generated after intranasal priming with L. murinus and S. pyogenes surprisingly express similar proinflammatory cytokines and are not CD25+/FoxP3+ T-regulatory cells when recirculating in the spleen. These findings suggest that when a commensal crosses the nasal epithelial barrier it induces a proinflammatory response similar to a pathogen but without causing disease.

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BACKGROUND: It is not known if reduced elicitation thresholds are evident among polysensitized individuals when using allergens to which the patients are already sensitized. Reduced elicitation thresholds may be an expression of increased reactivity in this patient group. OBJECTIVES: To examine and compare elicitation dose-response curves and elicitation thresholds in a polysensitized vs. a single/double-sensitized group for allergens to which the test subjects were already sensitized. PATIENTS/METHODS: Fifty-one patients (13 polysensitized and 38 single/double-sensitized) were patch tested with nickel sulphate, methyldibromo glutaronitrile (MDBGN) and p-phenylenediamine (PPD) in dilution series. The ratio between the doses eliciting a response in 50% of patients in the two groups was used as the measure for relative sensitivity. RESULTS: The dose-response curves of the polysensitized group for MDBGN and PPD were shifted to the right, and for nickel sulphate shifted to the left, compared with the single/double-sensitized group. The relative sensitivity for each of the three allergens and a combined relative sensitivity for all three allergens were not significantly different when comparing the polysensitized and single/double-sensitized groups. CONCLUSION: No increased sensitivity, in the form of distinct elicitation thresholds, could be demonstrated in polysensitized individuals compared with individuals with one or two contact allergies.

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BACKGROUND: Methyldibromoglutaronitrile (MDBGN) is a preservative, which was approved for use in cosmetics in the mid-1980s. The incidence of allergy to MDBGN rose during the 1990s, but is now decreasing due to regulatory intervention. Experimental studies with other allergens have shown a significant relationship between the patch test and the repeated open application test (ROAT) reactivity. OBJECTIVES: To study the relationship between elicitation threshold doses at single occluded exposure and repeated open application, using MDBGN as the allergen. METHODS: Eighteen subjects allergic to MDBGN were tested with a dilution series of MDBGN in a patch test and a ROAT (duration up to 21 days). Seventeen people with no MDBGN allergy were included as a control group for the ROAT. RESULTS: The response frequency for the ROAT (in microg MDBGN cm(-2) per application) was significantly higher than the response frequency for the patch test, while the response frequency for the accumulated ROAT dose, at 1, 2 and 3 weeks was very similar to the patch test response frequency; indeed there was no statistical significant difference. CONCLUSIONS: For elicitation of MDBGN allergy the response frequency for the patch test is lower than the response frequency (per application) for the ROAT, but approximately the same as the response frequency for the accumulated ROAT doses. This is important for risk assessment in general.

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BACKGROUND: The frequency of nickel allergy varies between different population groups. Exposure regulation has proven effective in decreasing the frequency. Experimental studies with other allergens have shown a significant relation between patch test reactivity and repeated open application test (ROAT) reactivity. OBJECTIVES: This study was aimed at determining the elicitation threshold in nickel-allergic individuals in a patch test and a ROAT, and comparing the threshold from these two test methods. METHODS: Twenty nickel-allergic persons were tested with a dilution series of 19 concentrations in a patch test and a dilution series of three concentrations in a ROAT, with duration of up to 21 days. Eighteen persons with no nickel allergy were included as control group for the ROAT. RESULTS: The predicted dose which will elicit a reaction in 10% of allergic individuals was calculated to be 0.78 microg nickel cm(-2) in the patch test. The threshold for the ROAT (in microg nickel cm(-2) per application) was significantly lower than the threshold for the patch test, while the dose-response for the accumulated ROAT dose at 1 week, 2 weeks and 3 weeks was very similar to the patch test dose-response; indeed, there was no statistically significant difference. CONCLUSIONS: For elicitation of nickel allergy the elicitation threshold for the patch test is higher than the elicitation threshold (per application) for the ROAT, but is approximately the same as the accumulated elicitation threshold for the ROAT. This may be important for risk assessment based on dose-response results from allergic patients.

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OBJECTIVES: To determine if the Pregnancy Risk Assessment Monitoring System (PRAMS) is a unique and valuable MCH data source and an effective mechanism for states to collect MCH data, and to assess if recent changes in it have improved efficiency and flexibility. METHODS: Each component of the PRAMS methodology is described: sampling and stratification, data collection, questionnaire, and data management and weighting. To assess effectiveness, we calculated response rates, contact rates, cooperation rates, refusal rates, and questionnaire completion rates. Logistic regression was used to examine the relationship between maternal and infant characteristics and the likelihood of response. Four criteria were defined to measure improvement in PRAMS functioning. RESULTS: Overall response rates for the 11 states in 1996 ranged from 66% to 80%. Cooperation rates were high (85-99%), with contact rates somewhat lower (73-87%). Response rates were higher for women who were older, White, married, had more education, were first-time mothers, and had a normal-birthweight infant. In all states, parity and education were the most consistent predictors of response, followed by marital status and race. Between 1988-1990 and 1996-1999, the number of states and areas participating in PRAMS increased from 6 to 23, response rates improved, and the time for a state to start data collection and to obtain a weighted dataset both decreased. CONCLUSIONS: PRAMS is a unique and valuable MCH data source. The mail/telephone methodology used in PRAMS is an effective means of reaching most women who have recently given birth in the 11 states examined; however, some population subgroups are not reached as well as others. The system has become more efficient and flexible over time and more states now participate.

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OBJECTIVE: To investigate the effectiveness of a topically applied emulsion of an analgesic ammonium solution for the temporary treatment of pain associated with arthritis, tendinitis and bursitis. DESIGN: 100 subjects in a single center, presenting with chronic pain associated with arthritis, tendinitis, or bursitis trialed against placebo in a double-blind cross-over protocol. MAIN OUTCOME MEASURES: Measures of treatment success include reduction in pain, improvement in clinical and/or mechanical evaluations, and evaluation of local and systemic adverse effects. Analysis was conducted at two weeks, after one week's clearance, and again after two weeks. RESULTS: For chronic neuralgia associated with arthritis, tendinitis, and bursitis, the test material had a positive effect at temporary pain reduction. Several subjects also recorded improvements in mechanical evaluations from baseline. Withdrawals due to systemic or local adverse reactions were minimal. CONCLUSION: A topical emulsion of a strong ammonium solution utilizing quaternary ammonium, enhanced with certain penetration enhancers, is effective for temporary relief of pain associated with arthritis, tendinitis, and bursitis.

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In 1984, the Palm Beach County (Florida) Medical Society faced the invasion of an HMO which, via an expensive advertising plan, urged Medicare recipients to enroll in a program that promised free health care. As physicians watched more and more of their older patients transfer to the HMO, they turned to their local medical society, which formulated a response. It launched a public information campaign designed to give patients the necessary facts about HMOs so they could make an informed decision about joining. The article describe the specific steps the physicians took to battle the new competition.

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