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Effect of pretreatment with fexofenadine on the safety of immunotherapy in patients with allergic rhinitis.

BACKGROUND: Allergen-specific immunotherapy, although not a cure, remains the only treatment available that can alter the natural course of an allergic disease. However, the risk of allergen specific immunotherapy-related systemic reactions (SRs), reported to occur in approximately 1% to 14% of patients and which can range from mild to fatal in seriousness, represents a barrier to implementing this unique and effective treatment option. OBJECTIVE: To explore the possibility that pretreatment with the H1-antihistamine fexofenadine could prevent the occurrence of severe SRs induced by immunotherapy in Japanese patients with allergic rhinitis. METHODS: In this open-label, multicenter study, 134 patients receiving immunotherapy for allergic rhinitis were randomized 1:1 to a group receiving pretreatment with fexofenadine hydrochloride (60 mg) 2 hours before immunization injection (n = 67) or to a control group receiving no pretreatment (n = 67). Patients were further grouped into those who received cedar pollen immunotherapy and those who received dust mite immunotherapy. RESULTS: Pretreatment with fexofenadine 2 hours before immunotherapy significantly reduced the occurrence of severe SRs (P = .03), significantly increased the proportion of patients receiving cedar pollen immunotherapy who achieved the target maintenance dose (TMD) (P = .03), and significantly reduced the length of time to attain the TMD (P = .047 and P = .003 for patients receiving cedar pollen and dust mite immunotherapy, respectively). CONCLUSIONS: This study suggests a novel role for fexofenadine in enhancing the safety of immunotherapy and increasing the proportion of patients achieving the TMD.

Adult↗

Determination of the carbonyl groups in native lignin utilizing Fourier transform Raman spectroscopy.

A near-infrared Fourier transform Raman (NIR-FTR) spectroscopic technique was utilized to determine the chemical structure of lignin in a woody matrix. In the NIR-FTR spectra of coniferaldehyde and coniferyl alcohol, the Raman bands for the carbonyl group and the alpha, beta unsaturated bond were detected at 1620 and 1660 cm(-1), respectively. These peaks were also found in the NIR-FTR spectra of chemically synthesized lignins, isolated lignin from conifer wood, and conifer wood meal. Upon the reduction of carbonyl groups in the lignin samples and wood meal, the band at 1620 cm(-1) disappeared; on the other hand, the band at 1660 cm(-1) remained unchanged. However, upon the oxidation of reduced lignin at the benzyl hydroxyl group using dicyanodichrolobenzoquinone, the band at 1620 cm(-1) clearly appeared, strongly suggesting that the band at 1620 cm(-1) can be assigned as a carbonyl marker band. The hydrogenation reaction optimized for the reduction of the unsaturated bond in lignin caused the disappearance of the band at 1660 cm(-1), indicating that the band at 1660 cm(-1) is an alpha, beta unsaturated bond marker band. The change in carbonyl content during the wood decay process was also shown to be monitored using the Raman intensity of the carbonyl marker band. It was indicated that the NIR-FTR spectroscopic techniques were suitable analytical method for a rapid and nondestructive analysis of wood samples.

Cedrus↗

Accurate estimation of forest carbon stocks by 3-D remote sensing of individual trees.

Forests are one of the most important carbon sinks on Earth. However, owing to the complex structure, variable geography, and large area of forests, accurate estimation of forest carbon stocks is still a challenge for both site surveying and remote sensing. For these reasons, the Kyoto Protocol requires the establishment of methodologies for estimating the carbon stocks of forests (Kyoto Protocol, Article 5). A possible solution to this challenge is to remotely measure the carbon stocks of every tree in an entire forest. Here, we present a methodology for estimating carbon stocks of a Japanese cedar forest by using a high-resolution, helicopter-borne 3-dimensional (3-D) scanning lidar system that measures the 3-D canopy structure of every tree in a forest. Results show that a digital image (10-cm mesh) of woody canopy can be acquired. The treetop can be detected automatically with a reasonable accuracy. The absolute error ranges for tree height measurements are within 42 cm. Allometric relationships of height to carbon stocks then permit estimation of total carbon storage by measurement of carbon stocks of every tree. Thus, we suggest that our methodology can be used to accurately estimate the carbon stocks of Japanese cedar forests at a stand scale. Periodic measurements will reveal changes in forest carbon stocks.

Automation↗

Role of an ABI3 homologue in dormancy maintenance of yellow-cedar seeds and in the activation of storage protein and Em gene promoters.

ABI3/VP1 proteins are members of a large group of transcription factors that act as intermediaries in regulating abscisic acid (ABA)-responsive genes during seed development, including those involved in reserve deposition, acquisition of desiccation tolerance and dormancy induction. CnABI3, an ABI3/VP1 gene homologue was recently cloned from yellow cedar, a conifer species that produces seeds that are deeply dormant at maturity. Here, we investigated whether the conifer ABI3/VP1 gene homologue shares characteristics with its angiosperm counterparts. CnABI3 was synthesized exclusively in seeds, with no detectable protein in leaves and roots. Stable expression of the CnABI3 gene in two transgenic tobacco lines previously transformed with chimeric constructs (vicilin and napin 5' regions linked to a beta-glucuronidase (GUS) gene-coding region) showed that the ectopic expression of the CnABI3 protein strongly activated both the vicilin and napin storage protein gene promoters in leaves and other vegetative tissues. GUS activities were up to more than 1000-fold of those in control plants. ABA had a synergistic effect, further enhancing GUS activity levels. When expressed transiently in yellow-cedar embryos, CnABI3 activated the expression of a chimeric Em-GUS gene in the presence of ABA. The role of CnABI3 in dormancy maintenance of yellow-cedar seeds was examined by monitoring the expression of the CnABI3 gene at the mRNA and protein levels before, during and after dormancy termination. CnABI3 protein was present in the megagametophyte and embryo of dormant mature and warm stratified seed, but declined during subsequent moist chilling, a treatment effective in breaking dormancy. In contrast, the protein was preserved (albeit in lower amounts) in seeds subjected to a control treatment (12 weeks in warm, moist conditions) that is ineffective in breaking dormancy. A decline in CnABI3 gene transcripts was also positively correlated with dormancy breakage, but did not occur during moist chilling itself, but rather during subsequent germination, indicating potential control at the post-transcriptional level.

Arabidopsis Proteins↗

Seasonal changes of humoral and cellular immune responses to Japanese cedar (Cryptomeria japonica) pollen allergens in Japanese monkeys (Macaca fuscata) with pollinosis.

The natural occurrence of Japanese cedar [Cryptomeria japonica (CJ)] pollinosis has been reported in Japanese monkeys (Macaca fuscata). The present study was designed to investigate seasonal changes in immunological reactions to CJ pollen allergens in monkeys with CJ pollinosis. Blood samples were collected from six monkeys with CJ pollinosis before and after CJ pollen season. Seasonal changes in specific IgE and IgG to major allergens (Cry j 1 and Cry j 2) were observed before and after CJ pollen season. The humoral responses decreased significantly before CJ pollen and increased after CJ pollen season. Similar seasonal changes in peripheral blood mononuclear cells proliferative responses to CJ allergens were observed before and after CJ pollen season. These humoral and cellular immune responses might serve as a biomarker for assessing new immunotherapies for monkeys with pollinosis.

Allergens↗

Fine-scale estimation of outcrossing in western redcedar with microsatellite assay of bulked DNA.

Western redcedar (Thuja plicata, Cupressaceae) is a self-fertile conifer with a mixed mating system and significant variation for outcrossing among populations. In this paper, we conducted a fine-scale study of mating system variation to identify correlates of outcrossing in natural populations. We examined variation for outcrossing within and among individual trees, and describe a new method to estimate outcrossing using bulked DNA samples. Bulking (assaying DNA tissues from several individuals simultaneously) increases the experimental power without increasing the experimental effort. We sampled 80 trees from four natural populations in southwestern British Columbia. From each tree, we sampled from up to six crown positions (three heights and inner vs outer branches). From each position, two samples of three seedlings each were bulked before DNA extractions. Using four microsatellite loci, we obtained outcrossing rates for each tree and for each of the six crown positions. We found individual tree selfing rates to increase with tree height in all four populations, but selfing rates did not differ among crown positions. The higher selfing rate of larger trees is probably due to their greater proportional contribution to local pollen clouds. Individual tree outcrossing rates ranged from 22 to 100% and the population outcrossing rates from 66 to 78%. Missed alleles due to bulking and the estimation method used both cause a downward bias in outcrossing rates, so that these estimates are probably lower than the actual outcrossing rates. Nevertheless, the trends we observed are not affected by systematic biases of estimation.

Cedrus↗

Seasonal atopic dermatitis in dogs sensitive to a major allergen of Japanese cedar (Cryptomeria japonica) pollen.

Three dogs were examined because of episodes of recurrent pruritic dermatitis in the spring, the season of Japanese cedar (Cryptomeria japonica, CJ) pollination in Japan. The dogs were shown to be sensitive to CJ pollen allergen using intradermal testing and antigen-specific IgE measurement. Fluorometric enzyme-linked immunosorbant assay (ELISA) showed increased concentrations of IgE specific to Cry j 1 and a negative result for Cry j 2 in the three dogs. The concentrations of IgE specific to Cry j 1 during the season of CJ pollination were higher than the concentrations found during the off-season in all the dogs, and the variation in the concentrations correlated with the variation in clinical signs. Peripheral blood mononuclear cells showed apparent proliferative responses to crude CJ pollen antigen and Cry j 1 during CJ pollination season. These findings indicated that Cry j 1 was the major allergen recognized by IgE and lymphocytes and resulted in the development of type I hypersensitivity to CJ pollen allergen in these atopic dogs.

Allergens↗

The effect of Japanese cedar-specific immunotherapy on cytokine production in peripheral blood mononuclear cells.

The most common cause of seasonal allergic rhinitis in Japan is the Japanese cedar (JC). Recently, a pullulan-conjugated antigen (CS-560) has been developed to reduce adverse effects and to enhance the effect of JC-specific immunotherapy (IT). If the mechanism of IT can be fully elucidated and the treatment can be used safely and with specificity, IT should be reconsidered as a superior treatment for JC pollinosis. Thirteen patients with JC pollinosis who received IT were compared to 10 patients who did not receive IT. All patients were followed through two pollen seasons by means of allergy diaries. Peripheral blood mononuclear cells (PBMC) were collected before IT and just before each pollen season, and these were stimulated with pollen extract. The concentrations of IL-4, IL-5, IL-13 and IFN-gamma in the culture supernatants were determined using an ELISA. Furthermore, messenger (m)RNA expressions of IL-4 and IL-5 from cultured PBMC were also studied. As a result of the allergy diaries, we confirmed the clinical efficacy of CS-560. The symptom-medication scores were significantly decreased by IT. The levels of IL-4, IL-5 and IL-13 declined only in the IT group. However, the level of IFN-gamma did not change in either group. IL-4 and IL-5 mRNA expressions were inhibited in the IT group compared to that in the non-IT group. In conclusion, specific IT for JC pollinosis using CS-560 clearly modified cytokine expression by PBMC.

Adult↗

Comparative study of two Japanese rhinoconjunctivitis quality-of-life questionnaires.

CONCLUSION: Two questionnaires were used to assess quality of life (QOL) in allergic rhinitis: the Japanese translation of the Rhino-conjunctivitis Quality of Life Questionnaire (RQLQJ) and an original Japanese QOL questionnaire (JRQLQ). Either questionnaire may be used to assess QOL depending on differences in target domains. OBJECTIVES: Although pollinosis is a common disease which has a major impact on patient QOL, no internationally standardized questionnaire has been available in Japan until now. The aim of this study was to compare two currently available QOL questionnaires for allergic rhinitis in Japan-the RQLQJ and JRQLQ-in terms of their appropriateness for clinical use and their psychometric properties. MATERIAL AND METHODS: A multicenter, inter-group, cross-sectional study was conducted in 187 adult symptomatic patients with Japanese cedar pollinosis in 2003. Patient scores on the two questionnaires were compared in terms of both overall and comparable domains. We also examined the acceptability, construct and reliability of both questionnaires. RESULTS: The questionnaires were highly correlated in terms of both overall and comparable domain scores. In addition, both questionnaires had equal and satisfactory psychometric validity, demonstrating that they are both useful tools for assessing QOL in rhinitis. However, when compared with each other, the JRQLQ focuses mainly on activities of daily life and is simpler, while the RQLQJ focuses mainly on rhinitis-related health and is more responsive.

Adult↗

Effects of the inhalation of diesel exhaust, Kanto loam dust, or diesel exhaust without particles on immune responses in mice exposed to Japanese cedar (Cryptomeria japonica) pollen.

To assess the potential enhancement by air-pollutants of immune responses in mice, especially with regard to allergen-specific immunoglobulin E (IgE) antibody production, female BDF(1) mice (60 mice in each group) were exposed to diesel exhaust (particles, 3.24 mg/m(3); nitrogen dioxide, 1.0 ppm: DE group), Kanto loam dust (particles, 3.29 mg/m(3); nitrogen dioxide, 0.01 ppm: KLD group), diesel exhaust without particles (particles, 0.01 mg/m(3); nitrogen dioxide, 1.1 ppm: DEG group), or clean air (pollen and control groups) for 16 h/day, 5 days/wk for 24 wk, as well as to Japanese cedar pollen (JCP) (around 550,000 grains of JCP/m(3)) for 2 days/wk in the same period. The control group was exposed to clean air alone throughout the experiment. The mean values for Japanese cedar pollen allergens (JCPAs)-specific immunoglobulin E (IgE) antibody titers in mice sera measured by enzyme-linked immunosorbent assay (ELISA) in the DE, KLD, and DEG groups were higher than that for the pollen alone group, but not significantly, after both 12 and 24 wk of exposure time. The percentages of animals expressing more than the minimum ELISA titer of JCPAs-specific IgE antibodies in each group were 22% (DE and pollen groups) and 27% (KLD and DEG groups) of the totals at wk 12, and no statistical differences were observed among the groups. However, at wk 24 in the DE, KLD, and DEG groups the responders comprised 73%, 63%, and 67%, respectively, significantly higher than the 33% for the pollen alone group. No significant differences were observed among the DE, KLD, and DEG groups. A slight dose-dependent increase of proliferative responses of mouse cervical lymph node cells to JCPAs in both DE and KLD groups was observed, but not in the DEG group. Remarkable decrease of interferon-gamma and significant increase of interleukin-4 in the nasal lavage fluid were apparent after DE or DEG exposure, but not in the KLD group. These results suggest that these air pollutants (DE, KLD, and DEG) enhance the production of IgE antibodies in mice, with similar adjuvant activities in each case. Furthermore, in the early phase of exposure in which sensitization occurred with exposure to pollen, the fine particles and gas components are considered to have exhibited different enhancing mechanisms in mice as follows: (1) The fine particles augmented production of IgE antibodies through activation of T lymphocytes, and (2) the gas components exhibited almost no action on T lymphocytes, but directly induced disorders of the cytokine network and augmented the production of IgE antibodies.

Air Pollutants↗

Effect of aromatic cedar mulch on Argentine ant (Hymenoptera: Formicidae) foraging activity and nest establishment.

In the laboratory, Argentine ant, Linepithema humile (Mayr), mortality was positively correlated to the length of an aromatic cedar mulch section that had to be crossed before food could be reached. When ants could access food without crossing the mulch, mortality was not correlated to mulch section length. In the field, Argentine ants showed a tendency to avoid aromatic cedar mulch as a nesting substrate. In plant beds alongside buildings the number of ant nests (pockets containing brood) found was not significantly different between aromatic cedar and cypress mulch. However, when pine straw mulch around oak trees was replaced with aromatic cedar or cypress mulch, a similar number of ant nests was found in the cypress mulch as in the original pine straw, whereas numbers in aromatic cedar mulch were significantly lower. Also, fewer ants were trailing on the trees surrounded by aromatic cedar mulch compared with cypress mulch or the original pine straw. The number of ants attracted to apple jelly baits placed alongside the buildings did not differ between mulch types; neither did the number of ant trails crossing the mulch beds around the buildings. We suggest that aromatic cedar mulch may help control Argentine ants and reduce insecticide input when applied in combination with conventional control methods.

Animals↗

IgE production after four routes of injections of Japanese cedar pollen allergen without adjuvant: crucial role of resident cells at intraperitoneal or intranasal injection site in the production of specific IgE toward the allergen.

The production of specific IgE antibodies directed toward cedar pollen correlates well with the onset of allergic rhinitis; but the mechanisms of allergen recognition as nonself and Ig class switch to IgE by the immune system are still not fully understood. In the present study, we injected cedar pollen into mice through 4 different routes (intranasal (i.n.), intraperitoneal (i.p.), intravenous (i.v.), and subcutaneous (s.c.)) without adjuvant 1 to 3 times, and determined time-dependent changes in the total and specific serum IgE levels compared with those in the serum levels of other isotype Igs. After an i.p. or i.n. injection of allergen into the mice, they produced a 1.5-to 1.7-fold increase in total IgE, but none in IgG, IgM, or IgA antibodies in their serum, whereas an i.v. or s.c. injection of allergen was inactive as an inducer of total IgE antibodies. Upon a 2nd (s.c.) injection of the allergen into the i.p. or i.n. sensitized mice, a large amount of allergen-specific IgE antibodies was found in the serum. In the case of i.v. or s.c. sensitized mice, however, they produced total, but not specific, IgE antibodies; and a 3rd (s.c.) injection of the allergen resulted in a large amount of specific IgE antibodies in the serum. These results imply that resident cells at the i.p. or i.n. injection site may play a crucial role in the efficient production of total and specific IgE antibodies toward the allergen.

Administration, Intranasal↗

Escherichia coli O157:H7 in environments of culture-positive cattle.

Outbreaks of Escherichia coli O157:H7 disease associated with animal exhibits have been reported with increasing frequency. Transmission can occur through contact with contaminated haircoats, bedding, farm structures, or water. We investigated the distribution and survival of E. coli O157:H7 in the immediate environments of individually housed, experimentally inoculated cattle by systematically culturing feed, bedding, water, haircoat, and feed bunk walls for E. coli O157:H7 for 3 months. Cedar chip bedding was the most frequently culture-positive environmental sample tested (27/96 or 28.15%). Among these, 12 (44.0%) of positive bedding samples were collected when the penned animal was fecal culture negative. Survival of E. coli O157:H7 in experimentally inoculated cedar chip bedding and in grass hay feed was determined at different temperatures. Survival was longest in feed at room temperature (60 days), but bacterial counts decreased over time. The possibility that urine plays a role in the environmental survival of E. coli O157:H7 was investigated. Cedar chip bedding moistened with sterile water or bovine urine was inoculated with E. coli O157:H7. Bedding moistened with urine supported growth of E. coli O157:H7, whereas inoculated bedding moistened with only water yielded decreasing numbers of bacteria over time. The findings that environmental samples were frequently positive for E. coli O157:H7 at times when animals were culture negative and that urine provided a substrate for E. coli O157:H7 growth have implications for understanding the on-farm ecology of this pathogen and for the safety of ruminant animal exhibits, particularly petting zoos and farms where children may enter animal pens.

Animal Feed↗

Prevalence of Japanese cedar pollinosis among schoolchildren in Japan.

BACKGROUND: Japanese cedar pollinosis is an important allergic rhinoconjunctivitis in Japan in spring. We investigated the relationship between the amount of pollen in the air and the prevalence of the disease and sensitization to Japanese cedar pollen in this ecological study. METHODS: The IgE antibody to Japanese cedar pollen (JCP-IgE) was determined in human serum and rhinoconjunctival symptoms were surveyed in 407-510 children in May or June every year from 1995 to 2001. Japanese cedar pollinosis was defined as being JCP-IgE >or=1.5 IU/ml and having any rhinoconjunctival symptom lasting 3 weeks or longer in March or April. RESULTS: Prevalence rates of Japanese cedar pollinosis were 13.8-22.9%. Prevalence rates of being JCP-IgE >or=1.5 IU/ml were 39.0-50.1%, and those of being JCP-IgE >or=15.01 IU/ml were 11.4-23.2%. All prevalence rates were significantly related to the amount of pollen in the air. The proportion of subjects with rhinoconjunctival symptoms was relatively constant in each stratum of low JCP-IgE levels (<0.35, 1.50-2.99, 3.0-14.9 IU/ml). CONCLUSION: High exposure to Japanese cedar pollen was associated with higher levels of JCP-IgE antibody and a high prevalence of Japanese cedar pollinosis. The relationship between the level of JCP-IgE and the proportion of subjects with symptoms was relatively constant.

Cedrus↗

Japanese cedar-pollen-specific IL-5 production in infants with atopic dermatitis.

BACKGROUND: Although food allergens and house dust mites are thought to contribute to the development of atopic dermatitis (AD) in infants, the influence of pollens has not yet been well defined. OBJECTIVE: This study attempted to clarify the effect of Japanese cedar pollens (JCPs), which are scattered in Japan between February and April, on AD in infants. METHODS: In the first study, seasonal changes in the number of patients who first visited our institute due to AD were analyzed by reviewing medical records of 184 infants with AD. In the second study, peripheral blood mononuclear cells from 81 children (50 infants <1 year and 31 older children) with AD were stimulated with a standardized JCP allergen. The production of IL-5 was measured and its correlation with the severity of AD in infants was analyzed. RESULTS: The number of infants who first visited the institute due to AD peaked in spring. JCP-specific IL-5 production began to increase immediately after the first contact with JCPs in infants with AD. The production of IL-5 in infants with AD exposed to JCPs was significantly higher than in control subjects (p < 0.002) or in AD infants never exposed to JCPs (p < 0.02). There was a significant positive correlation between IL-5 production and the severity of AD in infants (p < 0.0001). CONCLUSION: These results suggest that JCPs play an important role in the aggravation of infantile AD in spring by inducing IL-5 production.

Adolescent↗