Thromboxane A2 receptor +795T>C and chemoattractant receptor-homologous molecule expressed on Th2 cells -466T>C gene polymorphisms in patients with aspirin-exacerbated respiratory disease.

It is well known that aspirin-exacerbated respiratory disease (AERD) is more common in women than in men, however, whether gene polymorphisms of the thromboxane A2 receptor (TBXA2R) and chemoattractant receptor-homologous molecules expressed on Th2 cells (CRTH2) are associated with the susceptibility of AERD remains unknown. In this study, we examined the gene polymorphisms in a Japanese population. DNA specimens were obtained from the following three groups: 96 patients with AERD, 500 patients with aspirin-tolerant asthma (ATA) and 100 normal controls. The target DNA sequence of each gene was amplified, and an allelic discrimination assay for single nucleotide polymorphisms relating to expression of each gene was carried out. The frequencies of the CC/CT genotype of TBXA2R +795T>C were higher than those of the TT genotype in AERD patients compared to ATA patients (P=0.015). In female AERD patients, but not in males, frequencies of the CC/CT genotype were higher than those of the TT genotype of TBXA2R +795T>C compared to female ATA patients (P=0.013). Also, frequencies of the TT genotype of CRTH2 -466T>C were higher than those of the CC/CT genotype in AERD patients compared to ATA patients (P=0.034). In female AERD patients, but not in male, frequencies of the TT genotype were higher than those of the CC/CT genotype of CRTH2 -466T>C in AERD patients compared to female ATA patients (P=0.046). Based on our investigations, no significant relationship was found between the genotype and the clinical characteristics according to these gene polymorphisms in AERD patients. Our results suggest that an association between the TBXA2R and CRTH2 gene polymorphisms with AERD may exist in the Japanese population.

Arg16Gly ß2-adrenergic receptor gene polymorphism in Japanese patients with aspirin-exacerbated respiratory disease.

BACKGROUND: There has been no report that investigated ß(2)-adrenergic receptor (ADRB2) gene polymorphism in patients with aspirin-exacerbated respiratory disease (AERD). METHODS: DNA in the specimens in three groups of study subjects classified patients with AERD, patients with aspirin-tolerant asthma (ATA) and normal controls was extracted, and the target DNA sequence of the ADRB2 was amplified using a set of primers to generate an amplicon of 219 bp in length. Allelic discrimination assay for single nucleotide polymorphisms relating to the ADRB2 gene expression was carried out by using a previously described single nucleotide polymorphism detective system, sequence-specific thermal-elution chromatography. RESULTS: The frequency of the Gly variant allele in patients with AERD was significantly lower than that in patients with ATA (p = 0.007), and the odds ratio (OR) of AERD to ATA associated with wild-type ArgArg homozygote was 3.300. Frequencies of wild-type ArgArg homozygote are significantly higher than those of variant-type ArgGly/GlyGly genotype in patients with AERD compared with those with ATA (p < 0.001, OR = 3.153). In patients with AERD, frequencies of wild-type ArgArg homozygote in both female and male patients are significantly higher than those of variant-type ArgGly/GlyGly genotype in male patients compared with those with ATA (p < 0.001, OR = 5.128 and p = 0.007, OR = 4.367, respectively). Also, in patients with AERD, frequencies of wild-type ArgArg homozygote in female patients are significantly higher than those of variant-type ArgGly/GlyGly genotype in female patients compared with those with ATA (p = 0.002, OR = 2.825). CONCLUSIONS: We were the first to analyze Arg16Gly ADRB2 gene polymorphism in Japanese patients with AERD, and showed that Arg16Gly ADRB2 gene polymorphism in Japanese patients with AERD is different from that in the patients with ATA.

Urinary eosinophil-derived neurotoxin concentrations in patients with atopic dermatitis: a useful clinical marker for disease activity.

BACKGROUND: It has been reported that measurements of eosinophil-derived neurotoxin (EDN) may be useful for identifying eosinophil activities in allergic diseases including atopic dermatitis. METHODS: EDN concentrations in the urine were measured by enzyme-linked immunosorbent assay, and the number of eosinophils in the peripheral blood was counted in 30 patients with atopic dermatitis. The severity of atopic dermatitis was graded on the criteria proposed by Rajka and Langeland. The disease activity was assessed by each patient on a visual analogue scale (VAS). RESULTS: Urinary concentrations of EDN in patients with atopic dermatitis showed a significant positive correlation with disease severity. Urine EDN concentrations also correlated with VAS scores for itching, skin condition, overall skin symptoms and total VAS score, but not with the VAS score for skin dryness. Urinary EDN concentrations did not correlate with the number of eosinophils in the peripheral blood. CONCLUSIONS: The urinary EDN concentration in patients with atopic dermatitis is a useful clinical marker for monitoring disease activity.

Mast cells in cutaneous allergic vasculitis: a case report.

BACKGROUND: The mechanism of cutaneous allergic vasculitis still remains unclear, and to the best of our knowledge, no case has been reported in the literature in which the number of mast cells was examined. METHODS: A 33-year-old woman, with a past history of allergic rhinitis due to Japanese cedar and Phleum pratense (timothy), presented with a chief complaint of palpable papules on both lower legs in December 2002. On blood examination, peripheral blood eosinophilia was present, but all other examinations for immunologic diseases were negative, including specific IgE. We suspected cutaneous allergic vasculitis and performed skin biopsy. RESULTS: In December 2002, histological examination of biopsy specimens of the skin lesions showed leukocytoclastic vasculitis. The diagnosis of cutaneous allergic vasculitis was made based on the clinical symptoms and the pathological findings of biopsy specimens. Immunohistochemical staining for human mast cell tryptase using monoclonal antibody against human mast cell tryptase showed an accumulation of mast cells. Treatment with oral corticosteroid resulted in the disappearance of clinical symptoms, and the steroid tapered. A second skin biopsy was performed in June 2005 after informed consent was obtained. Histological examination showed no findings of leukocytoclastic vasculitis, and the number of mast cells had decreased. She has been well without treatment. CONCLUSIONS: Mast cells may increase in the skin lesion of cutaneous allergic vasculitis.

Quantitative analysis of mast cells in benign and malignant breast lesions. Immunohistochemical study on formalin-fixed, paraffin-embedded tissues.

BACKGROUND: It has been reported that the number of mast cells was significantly greater in malignant breast carcinomas than in benign breast lesions. This was due to tryptase-containing mast cells while tryptase, chymase-containing mast cells had no effect. However, analysis of mast cells in breast carcinomas and benign breast lesions based on their histological findings remains to be elucidated. METHODS: Using immunohistochemical methods morphological examinations of mast cells were undertaken in benign and malignant breast tissues from 51 patients (30 benign, 21 malignant), which were formalin-fixed and paraffin-embedded. In the study with malignant breast tissues, samples of malignant tissues and adjacent healthy tissues were obtained from a single patient, and the number of mast cells was compared. RESULTS: Among benign breast tissues, the number of mast cells in intracanalicular fibroadenoma was significantly lower than that in pericanalicular fibroadenoma as well as that in mastopathy. The number of mast cells was significantly greater in malignant lesions than that in benign lesions. The number of mast cells in scirrhous carcinoma and that in solid-tubular carcinoma were significantly increased compared with that in adjacent healthy tissues. In addition, the number of mast cells in scirrhous carcinoma was highest among breast carcinomas, and significantly greater than that in papillotubular carcinoma. CONCLUSION: We were the first to find the significant lower number of mast cells in intracanalicular breast fibroadenoma when compared with that in pericanalicular fibroadenoma as well as that in mastopathy. Moreover, the number of mast cells in scirrhous carcinoma was significantly greater than that in papillotubular carcinoma.