A validation study of the Japanese version of the Angioedema Activity Score (AAS) and the Angioedema Quality of Life Questionnaire (AE-QoL).

BACKGROUND: Recurrent angioedema (RecAE) has a substantial impact on patients' daily lives. However, there have been no disease-specific patient-reported outcomes (PROs) available in Japan to measure disease activity and health-related QoL impairment in such patients. METHODS: Japanese versions of the Angioedema Activity Score (AAS) and the Angioedema Quality of Life Questionnaire (AE-QoL) were examined for their validity and reliability. By using these questionnaires, the relationship between disease activity and QoL impairment among the Japanese population of RecAE were analyzed in real-world setting. RESULTS: The Japanese AAS and AE-QoL domains showed good internal consistency of 0.967 and > 0.835. For known group validity, AAS28 and AE-QoL total scores were higher in more severe patients than those with milder disease and QoL impairment, respectively. AAS28 showed strong correlation with indexes of disease activity, while the AE-QoL total score correlated with Dermatology Life Quality Index (DLQI). Sufficient reproductivity of the AAS and AE-QoL was shown by their intraclass correlation coefficients of 0.890 and 0.700. The Japanese population is characterized by the total score of AAS28, 34.3 ± 38.8 (mean ± SD); and AE-QoL, 38.7 ± 25.2. Each domain score of AE-QoL was 32.4 ± 29.7 in "Functioning", 35.0 ± 27.8 in "Fatigue/mood", 50.7 ± 30.6 in "Fears/shame", or 24.7 ± 29.8 in "Food". Changes in AAS28 and AE-QoL positively correlated to Patient global assessment of disease activity and DLQI, respectively. CONCLUSIONS: The Japanese AAS and AE-QoL are valid and reliable instruments for Japanese patients with RecAE, and active disease affecting QoL. They help assess disease activity and QoL of RecAE in routine patient care and clinical trials.

Cochineal dye-induced immediate allergy: Review of Japanese cases and proposed new diagnostic chart.

BACKGROUND: Cochineal dye is used worldwide as a red coloring in foods, drinks, cosmetics, quasi-drugs, and drugs. The main component of the red color is carminic acid (CA). Carmine is an aluminum- or calcium-chelated product of CA. CA and carmine usually contain contaminating proteins, including a 38-kDa protein thought to be the primary allergen. Severe allergic reactions manifest as anaphylaxis. The aim of this study was to review all Japanese reported cases and propose useful diagnostic chart. METHODS: All reported Japanese cases of cochineal dye-induced immediate allergy were reviewed, and newly registered cases were examined by skin prick test (SPT) with cochineal extract (CE) and measurement of CE and carmine-specific serum IgE test. Two-dimensional (2D) western blotting using patient serum was conducted to identify the antigen. RESULTS: Twenty-two Japanese cases have been reported. SPT and the level of specific IgE test indicated that six cases should be newly registered as cochineal dye allergy. All cases were adult females, and all cases except three involved anaphylaxis; 13 cases involved past history of local symptoms associated with cosmetics use. Japanese strawberry juice and fish-meat sausage, and European processed foods (especially macarons made in France) and drinks were recent major sources of allergen. 2D western blotting showed that patient IgE reacted to the 38-kDa protein and other proteins. Serum from healthy controls also weakly reacted with these proteins. CONCLUSIONS: SPT with CE and determination of the level of CE and carmine-specific IgE test are useful methods for the diagnosis of cochineal dye allergy.

Characterization of causative allergens for wheat-dependent exercise-induced anaphylaxis sensitized with hydrolyzed wheat proteins in facial soap.

BACKGROUND: In Japan, hydrolyzed wheat proteins (HWP) have been reported to cause wheat-dependent exercise-induced anaphylaxis (WDEIA) by transcutaneous sensitization using HWP-containing soap. Patients develop allergic reactions not only with soap use, but also with exercise after the intake of wheat protein (WP). ω5-Gliadin and HMW-glutenin were identified as major allergens in conventional WP-WDEIA patients. However, the allergens in HWP-WDEIA have yet to be elucidated. METHODS: Sera were obtained from 22 patients with HWP-sensitized WDEIA. The allergenic activities of HWP and six recombinant wheat gluten proteins, including α/ß-, γ-, ω1,2- and ω5-gliadin and low- and high molecular weight (HMW)-glutenins, were characterized by immunoblot analysis and histamine releasing test. IgE-binding epitopes were identified using arrays of overlapping peptides synthesized on SPOTs membrane. RESULTS: Immunoblot analysis showed that IgE antibodies (Abs) from HWP-WDEIA bound to α/ß-, γ- and ω1,2-gliadin. Recombinant γ-gliadin induced significant histamine release from basophils in eight of 11 patients with HWP-WDEIA. An IgE-binding epitope "QPQQPFPQ" was identified within the primary sequence of γ-gliadin, and the deamidated peptide containing the "PEEPFP" sequence bound with IgE Abs more strongly compared to the native epitope-peptide. The epitope-peptide inhibited IgE-binding to HWP, indicating that the specific IgE to HWP cross-reacts with γ-gliadin. CONCLUSIONS: HWP-WDEIA patients could be sensitized to HWP containing a PEEPFP sequence, and WDEIA symptoms after WP ingestion could partly be induced by γ-gliadin. These findings could be useful to help develop tools for diagnosis and desensitization therapy for HWP-WDEIA.

[Two cases of royal jelly allergy provoked the symptoms at the time of their first intake].

Two young women were suffered from several symptoms after the intake of royal jelly at their first time. According to the positive skin prick test reactions of raw royal jelly, royal jelly allergy was diagnosed. As the reasons why the symptoms appeared at the time of their first intake, we guessed the possibility that 1) they had been sensitized for royal jelly formerly, or 2) their symptoms were induced by the cross-reactivity between royal jelly and other allergens such as bee, honey and pollens. As to our cases, no related allergens were found in one case, but in another case co-existence of mugwort allergy was suspected from the results of both skin prick test and specific IgE titers. Originally royal jelly allergy has been regarded as class 1 allergic reaction developed by the sensitization of itself. But we speculated the possibility that there can also be cases of class 2 royal jelly allergy by the mechanism of cross-reaction with pollens.

Changes in the characteristics of patients with latex allergy from 1999 to 2014.

OBJECTIVES: We conducted a multicenter study using the same questionnaire in 1999 and 2014 to investigate changes in the characteristics of patients with latex allergy. METHODS: We mailed questionnaires on latex allergy to hospitals in Japan that were members of the Japanese Latex Allergy Society. RESULTS: We compared the 25 responses received in 2014 and the 81 responses received in 1999. With regard to the age distribution, the number of patients with latex allergy in their 20s declined significantly from 1999 to 2014 (P=0.004). The largest proportion of latex allergy cases was observed among those aged <10 years. The incidence of cases caused by medical rubber gloves decreased significantly (P=0.004). Moreover, latex-fruit syndrome increased from 15% to 40% (P=0.006). CONCLUSIONS: Our findings indicate that the frequency of occurrence of latex allergy in people in their 20s decreased from 1999 to 2014. The largest proportion of latex allergy cases was observed among those aged <10 years. Future measures to protect children are required.

[Two cases of apiaceae spice allergy].

BACKGROUND: Many cases of spice allergy have been reported especially from Scandinavian countries, but in contrast there are few reports in Japan. This time we experienced two cases of apiaceae spice allergy and practiced some kinds of examinations. We report here these two cases with the consideration concerning mechanism of spice allergy. METHODS AND SUBJECTS: We practiced 1) specific IgE of pollens and foods, 2) prick tests of spices and apiaceae vesitables, 3) immunoblot of spices, against two cases suspected spice allergy from their clinical courses. Clinically Case 1 32 y.o. male had been no history of pollinosis, in contrast Case 2 46 y.o. female had been suffered from pollinosis during spring and autumn seasons. RESULTS: In Case 1 the scores of specific IgE of pollens were almost negative and immunoblot examination of spices revealed positive reaction at the site of 10 approximately 12 kDa and 60 kDa. In Case 2 the scores of specific IgE of pollens were positive in many species and immunoblot examination of spices reacted positively at the site of 14 kDa and 60 kDa. Both of them showed positive reactions against many kinds of apiaceae spices in prick tests, so we diagnosed them as apiaceae spice allergy. CONCLUSION: According to these results we suspected Case 1 as class 1 allergy induced by the sensitization of spices themselves and Case 2 as class 2 allergy caused by the cross reactions with pollinosis. So there may be some different mechanisms in the occurrence of spice allergy. In the future the occurrence of spice allergy will be supposed to increase and it will be necessary for us to pay much more attention to spice allergy even in Japan.

[Four cases of wheat-dependent exercise-induced anaphylaxis with negative gluten cap-rast score].

BACKGROUND: Either omega-5 gliadin or high molecular weight glutenin is known to be a major allergen in wheat-dependent exercise-induced anaphylaxis (WDEIA). It is generally considered that gluten specific IgE score is more reliable than that of wheat specific IgE score for the diagnosis of WDEIA. Our aim was to verify the significance of gluten specific IgE in the diagnosis of WDEIA. METHODS: We evaluated the result of gluten CAP-RAST score and omega-5 gliadin specific IgE score on four WDEIA patients who visited our hospital during the years 2004 and 2005, whose diagnosis were onfirmed by prick tests, immunoblot tests and provocation tests. RESULTS: Contrary to our expectations, all four patients showed negative gluten CAP-RAST scores, however all patient's omega-5 gliadin specific IgE scores were positive. CONCLUSION: Our results suggest that gluten specific CAP-RAST score is unreliable in the diagnosis of WDEIA. On the other hand omega-5 gliadin specific IgE score is possibly a better candidate as a diagnostic tool for WDEIA.

[Four cases of pollen-food allergy syndrome suspected the cross reactivity including latex].

BACKGROUND: Generally it is recognized that the occurrence of fruit allergy is attributed not to the sensitization of itself but to the cross reactivity with pollens or latex. But the relationship as to the sensitization between pollen and latex is obscure. So we aimed to investigate the relation of sensitization among pollens, fruits and latex. METHODS: We tried to examine latex-specific IgE titer and practice skin prick test of latex for the patients of pollen-food allergy syndrome. RESULTS: It was confirmed that some patients of pollen-food allergy syndrome showed positive reactions against both specific IgE and skin prick test of latex, though they could tolerate latex products in their daily lives. We present here four patients of such clinical courses concretely. CONCLUSION: The patients of pollen-food allergy syndrome should be practiced examination about latex allergy, even if they can use latex products without any symptoms. And more if positive results are obtained, additional examination such as immunoblot and IgE RAST inhibition test are recommended to practice in order to clarify the unresolved problems, such as 1) which factor is the major allergen to cause cross-reactivity among these three factors? 2) what occurs if patients of same clinical courses with our cases continue to use latex products? Further investigation will be indispensable to resolve these problems in the future.

[Three cases of centipede allergy--analysis of cross reactivity with bee allergy].

BACKGROUND: We experienced three cases of patients who suffered from systemic urticaria and systemic symptoms such as general fatigue and dyspnea which occurred just after the sting of centipede. The result of prick test by centipede venom revealed positive reaction in all three patients, so we diagnosed the symptoms of them as immediate type allergic reaction against centipede venom. And more there have been some reports documented the relationship between centipede allergy and bee allergy, so we added the examination about bee allergy on these three patients. METHODS: The measurement of bee venom specific IgE was practiced on all three patients and intradermal skin test about bee venom was done only on one patient. Moreover we also practiced prick test of centipede venom against another three patients who were diagnosed as having bee allergy. RESULTS: All patients of centipede allergy showed positive reaction for the specific IgE antibody of Wasp and/or Honeybee and one patient who was practiced skin test also reacted positively against Wasp and Yellow Jacket venom. But none of three patients of bee allergy showed positive reaction against centipede venom. CONCLUSION: According to these results we suspected that there lies some relationship between centipede allergy and bee allergy. But it is supposed that only little involvement of centipede allergy was concerned among the patients of bee allergy. Until now there have been only a few reports as to the centipede allergy. But actually we guess it may be the phenomenon that could occur frequently.

[A clinical study of deceased cases of pulmonary M. Avium complex (MAC) disease--: in contrast with survived cases followed-up for 5 years or longer].

We performed a clinical study of pulmonary M. avium complex (MAC) disease comparing decreased cases and survived cases followed-up for 5 years or longer. The results were as follows: 1. At the time of starting the initial medical treatment for pulmonary MAC disease, the deceased cases were older than the survived cases, and the deceased cases were severe than the survived cases in clinical conditions. The spread of the lesions was more extensive and cavities were more frequently observed in the deceased cases than in the survived cases. 2. We classified the clinical pattern of pulmonary MAC disease into a primary infection type and a secondary infection type. Then, we subclassified the primary infection type into a localized type, which contained a tuberculosis-like type and middle, lingular or other lobar pneumonia type, and a diffuse type. The secondary infection type was more frequent in the deceased cases than in the survived cases, and any middle, lingular or other lobar pneumonia type was not observed in the deceased cases. 3. We classified the mode of progression of pulmonary MAC disease in the deceased cases into a tuberculosis-like progression and a diffuse progression. The tuberculosis-like type and the secondary infection type frequently showed the tuberculosis-like progression and the diffuse type frequently showed the diffuse progression. The patients who showed the tuberculosis-like progression were frequently sputum culture positive for MAC, while all patients showing the diffuse progression were culture negative at the time of death. An interval from the estimated onset of the disease to death was shorter in the tuberculosis-like progression type than in the diffuse progression type.

[A clinical study on cases with pulmonary M. avium complex (MAC) disease followed up for more than 10 years].

We performed a clinical study on 22 cases with pulmonary M. avium complex disease followed up for more than 10 years. The mean age of these patients at the first visit was 60.1 years old and the extent of the disease among them was minimum or moderate. The progression of the disease was relatively slow. There were 5 cases of tuberculosis-like type and 11 cases of nodular-bronchiectasis type among the primary infection type and 6 cases of the secondary infection type. Classifying these cases by the grade of progression on chest X-ray findings, 2 cases improved, 11 cases slightly progressed, 4 cases moderately progressed and 5 cases severely progressed. Seven cases of the nodular-bronchiectasis type of the primary infection type were observed among 11 slightly progressed cases. This suggested that the prognosis of cases with nodular-bronchiectasis type was relatively good. The frequency of a reaggravation of chest X-ray findings was significantly higher in the severely progressed cases than in the slightly and moderately progressed cases. Generally, the number of used drugs was more and the duration of treatment was longer in the severely progressed cases. This suggested that these cases were intractable. The results of sputum culture for M. avium complex were consistent with the progression of the disease shown on chest X-ray findings among many cases. However, sputum culture negative was observed in some cases with the nodular-bronchiectasis type in spite of the reaggravation on chest X-ray findings. On the other hand, there were some cases in which few reaggravation was observed in spite of continued sputum culture positive. Based on these results, we made some remarks on the treatment and management of pulmonary M. avium complex disease.

[A case of cervical and mediastinal lymph nodes tuberculosis, tuberculous pleurisy, spinal caries and cold abscess in the anterior chest wall].

A 61-year-old woman with schizophrenia that had been treated in a psychiatric hospital was admitted to our hospital because of subileus and back pain. Though subileus was improved, she had a sudden attack of fever 7 days later and developed right pleural effusion, a cold abscess in the anterior chest wall and swelling of a thumb-sized right cervical lymph node which broke through the skin. We made a diagnosis of cervical and mediastinal lymph nodes tuberculosis, tuberculous pleurisy, spinal caries and cold abscess in the anterior chest wall due to the biopsy findings of the specimen taken from the cervical lymph node, examination of pleural effusion, chest CT, bacteriological examination of the cold abscess and spinal MRI. We started chemotherapy with the antituberculous drugs (HRSZ) and symptoms except back pain improved. She complained of paresis of the both lower extremities, which completely paralyzed 8 months later in spite of continued chemotherapy. Thereafter her paralysis was gradually improved and she was able to walk by herself after 12 months chemotherapy.

[Case of chronic eosinophilic bronchiolitis associated with bronchial asthma].

A 62 year-old woman presented with diffuse, centriacinar nodular densities on chest radiography and CT, and an increase of peripheral blood eosinophils, four years after diagnosis of bronchial asthma. Diffuse panbronchiolitis was diagnosed, and was treated with erythromycin for a long period. One year later, she noticed exertional dyspnea, and her chest radiograph showed increased nodular densities. Lung biopsy under video-assisted thoracoscopy was performed, and revealed chronic bronchiolitis with eosinophilic infiltration, and focal, peribronchiolar eosinophilic infiltration in the alveolar septa and alveoli. She was treated with prednisolone, and her symptoms and nodular densities on chest radiography and CT were improved. We consider that the clinico-pathological findings of this case are consistent with those of chronic eosinophilic bronchiolitis, which has recently been reported in Japan. This case is different from previously reported ones in that eosinophilic bronchiolitis appeared in the course of bronchial asthma, suggesting the possibility that eosinophilic bronchiolitis may be accompanied with bronchial asthma or eosinophilic pneumonia.

[A case of pulmonary mucormycosis diagnosed through video-assisted thoracoscopic surgery--report of a case].

We report a case of pulmonary mucormycosis successfully treated by medical methods only. The patient was a 51-year-old man with diabetes mellitus who presented with general fatigue and appetite loss. His chest radiograph and CT scan showed multiple thin-walled cavities in the left upper lobe. Because we could arrive at a clear diagnosis, video-assisted thoracoscopic surgery was performed. Lung biopsy of the left upper lobe revealed pulmonary mucormycosis. Our diagnosis was pulmonary mucormycosis with diabetes mellitus and alcohol addiction. The patient was treated with antifungal drugs--mainly amphotericin-B--while the diabetes mellitus was well controlled, and his diet and nutritional state was improved, resulting in the disappearance of symptoms, improvement of the radiological findings, and the absence of any relapse of the disease of at least 3 years.

[Immunological studies in cases of pulmonary Mycobacterium avium complex infection without predisposing conditions].

Peripheral blood mononuclear cells (PBMCs) taken from 39 primary pulmonary MAC patients and 11 control subjects were stimulated in vitro with a protein antigen PPD-B derived from M. intracellulare. Then, the activated response of the peripheral blood lymphocytes (PBLs) and the production of interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) were measured. The 39 primary pulmonary MAC patients were divided into A and B groups the former patients satisfying all of the criteria for the diagnosis of nontuberculous mycobacterial disease proposed by the American Thoracic Society, with the exception of the bacteriologic criteria, and the latter, who satisfied all without exception. The 39 patients were also divided into 3 groups according to disease severity judged from chest CT features. Severity in grades 1, 2 and 3 groups were mild, moderate and severe, respectively. We compared the activated response of PBLs and the production of IFN-gamma and IL-10 by PBMCs of the control group and each patient group. The number of lymphocytes and activated T cells and the concentration of the IFN-gamma after stimulation with PPD-B were lower in each group of primary pulmonary MAC patients than in the control group. IL-10 was significantly higher in each group of primary pulmonary MAC patients than in the control group (36.6 +/- 11.8 pg/ml), and higher in group B (131.6 +/- 14.9) than in group A (81.1 +/- 31.5). There was no significant difference in the IL-10 concentration between the grade 1, 2 and 3 groups. These results suggested that the cell-mediated immunity of primary pulmonary MAC patients was suppressed as the disease progressed, and the increased production of IL-10 was related to this suppression.

Acylzirconocene Chloride as an "Unmasked" Acyl Anion.

Under mild conditions the acyl group of acylzirconocene chloride 1 formed from an alkene or alkyne and [(C5 H5 )2 ZrHCl] reacts as an "unmasked" acyl anion. The Lewis acid mediated reactions with aldehydes that yield α-ketol products in high yields demonstrate the versatility of this reagent for C-C coupling.

The Vocal Joystick: evaluation of voice-based cursor control techniques for assistive technology.

PURPOSE: Mouse control has become a crucial aspect of many modern day computer interactions. This poses a challenge for individuals with motor impairments or those whose use of hands is restricted due to situational constraints. We present a system called the Vocal Joystick which allows the user to continuously control the mouse cursor by varying vocal parameters such as vowel quality, loudness and pitch. METHOD: Evaluations were conducted to characterize expert performance capability of the Vocal Joystick, and to compare novice user performance and preference for the Vocal Joystick and two other existing speech based cursor control methods. RESULTS: Our results show that Fitts' law, a well adopted model of human motor performance for movement tasks, is a good predictor of the speed - accuracy tradeoff for the Vocal Joystick, and suggests that the optimal performance of the Vocal Joystick may be comparable to that of a conventional hand-operated joystick. Novice user evaluations show that the Vocal Joystick can be used by people without extensive training, and that it presents a viable alternative to existing speech-based cursor control methods. CONCLUSIONS: The Vocal Joystick, with its ease of use, minimal setup requirement, and controllability, offers promise for providing an efficient method for cursor control and other forms of continuous input for individuals with motor impairments.

IFN-gamma-inducible expression of thymus and activation-regulated chemokine/CCL17 and macrophage-derived chemokine/CCL22 in epidermal keratinocytes and their roles in atopic dermatitis.

Thymus and activation-regulated chemokine (TARC)/CCL17 and macrophage-derived chemokine (MDC)/CCL22 are a pair of CC chemokines known to selectively attract T(h)2 type memory T cells via CCR4. Here we examined circulating levels of TARC and MDC in patients with atopic dermatitis (AD) and control subjects by using plasma samples, which reflect blood contents of chemokines more accurately than serum samples. The plasma levels of TARC and MDC were significantly elevated in AD patients. These values also strongly correlated with disease severity and serum lactate dehydrogenase levels, and weakly correlated with serum total IgE levels and blood eosinophilia. Previous studies demonstrated TARC immunoreactivity in the epidermal layer of AD lesional skin and production of TARC by a human keratinocytic cell line HaCaT upon stimulation with IFN-gamma. Here we demonstrated MDC immunoreactivity in the epidermal layer of AD skin at levels stronger than that of TARC. Furthermore, primary epidermal keratinocytes expressed both TARC and MDC mRNA upon stimulation with IFN-gamma, but efficiently secreted only MDC. These results suggest a post-transcriptional regulation in TARC production. IFN-gamma also induced TARC and MDC mRNA in mouse skin. Collectively, both TARC and MDC play important roles in the local accumulation of T(h)2 cells in AD lesional skin. Production of T(h)2-attracting chemokines by epidermal keratinocytes upon treatment with IFN-gamma, which is also the potent inducer of T(h)1-attracting chemokines, may underline the pivotal role of IFN-gamma in the chronic phase of AD where both T(h)1 and T(h)2 responses are mixed.