We investigated itch-associated responses (scratching) to mosquito bites and the role of histamine and mast cells in mosquito-induced itching in mice. Although the first bites of mosquito Aedes albopictus did not increase scratching, repeated bites increased scratching. The response was not diminished even after an interval of 2 months. Similarly, repeated intradermal (i.d.) injections of salivary gland extract (SGE) from Aedes albopictus increased scratching after SGE injection itself and mosquito bites. The scratching peaked within 10 min and almost subsided by 60 min. The opioid antagonist naloxone (1 mg/kg, s.c.) inhibited scratching following SGE injection. Although the non-sedative H₁-histamine-receptor antagonist terfenadine (30 mg/kg, p.o.) significantly suppressed scratching induced by histamine (100 nmol/site, i.d.) in either naive or mosquito-sensitized mice, it did not affect mosquito-induced scratching in mosquito-sensitized mice. Repeated injections of SGE increased scratching in mast cell-deficient (WBB6F1-W/W^v) mice as well as in normal (WBB6F1-+/ +) littermates. Repeated exposure to mosquito bites roughly doubled serum concentrations of total IgE and IgG₁, but not IgG_2a. Repeated injections of SGE markedly increased plasma extravasation induced by mosquito bites and such an increase was almost completely suppressed by terfenadine (30 mg/kg, p.o.). The results show the presence of histamine-mediated and histamine-independent mechanisms in cutaneous itching and suggest that histamine probably released from mast cells does not play an important role in itching in immediate allergic reaction. Our murine model of mosquito itching may be useful for studying the mechanisms of immediate allergic itching.

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Hypersensitivity to mosquito bites (HMB) is a rare disease characterized by transient intense skin reaction and systemic inflammation. Clinical presentation of HMB resembles other mosquito allergic responses, and it can also be difficult to clinically distinguish HMB from other severe allergic reactions. However, a distinctive pathophysiology underlies HMB.
HMB belongs to a category of Epstein-Barr virus (EBV)-associated natural killer (NK) cell lymphoproliferative disorders (LPD). Hence, HMB may progress to systemic diseases, such as hemophagocytic lymphohistiocytosis, chronic active EBV disease, and EBV-associated malignancies.
A triad of elevated serum IgE, NK lymphocytosis, and detection of EBV DNA in peripheral blood is commonly observed, and identification of EBV-infected NK cells usually facilitates the diagnosis. However, the effective treatment is limited, and its precise etiology remains unknown.
Local CD4+ T cell proliferation triggered by mosquito bites appears to help induce EBV reactivation and EBV-infected NK-cell proliferation. These immunological interactions may explain the transient HMB signs and symptoms and the disease progression toward malignant LPD.
Further research to elucidate the mechanism of HMB is warranted for better diagnosis and treatment of HMB and other forms of EBV-associated LPD.

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We examined whether azelastine would inhibit itch-associated responses of mice to mosquito allergy. Repeated injections of mosquito salivary gland extract increased scratching and sensory nerve activity. Azelastine inhibited the increased scratching and nerve activity, while terfenadine was without effects. Dexamethasone did not affect the increased scratching. Azelastine suppressed high K⁺-induced increase in intracellular free Ca²⁺ in primary cultures of mouse sensory neurons. Direct inhibition by azelastine of sensory neurons may be at least involved in the anti-pruritic effect of azelastine. Histamine, substance P, and leukotriene B₄ may not play a key role in the itching of mosquito allergy.

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蚊刺反応は刺刺回数によって変化する。始めは無反応(type I)で、刺刺回数の増加につれ、遅延反応(蚊刺24時間後をピークとする硬結·紅斑)のみ(type II)、即時反応(蚊刺30分後をピークとする膨疹·紅斑)も生じる(type III)、即時反応のみ(type IV)、無反応(type V)と変化する。我々は162名の被験者を年齢群に分け、Aedes albopictusに刺された反応が年齢群により変化することを過去に報告した。蚊刺反応がtype IIだった者1名(1歳:当時の年齢)とtype IIIだった者4名(4歳2名、5歳1名、6歳1名)に10年後にAedes albopictusを刺させ、蚊刺反応の変化を観察した。結果は全員typeは変化しなかったが、遅延反応は減弱した。type IIIの4名中3名は即時反応も減弱し、1名はわずかに増強した。

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Objective A dengue outbreak occurred in Japan 2014. We investigated the characteristics of dengue infection among Japanese.
Methods We investigated the medical charts retrospectively.
Patients The study participants are patients who came to our clinic between 2008 and 2014.
Results We investigated 4 domestic cases and 46 imported cases of Japanese with laboratory confirmation of dengue. Major symptoms were fever (100%), rash (86%), fatigue (84%), headache (81%), joint pain (66%), muscle pain (49%), and bleeding (6%). A late rash that appeared near the time of fever resolution was observed in 37 cases (74%). A total of 38/43 (88%) cases had low WBC count (<3,500 /μL) during the febrile period, 42/48 (88%) cases had a low platelet (PLT) count (<130×10³/μL), and 44/50 (88%) cases had a C-reactive protein (CRP) <2.0 mg/dL.
Conclusion Patients with a high fever, late rash, fever-associated leukopenia, low PLT count, low CRP, and elevated aminotransferases are generally suspected of having a dengue infection.

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要旨 背景：2014 年，60 年以上なかったデング熱の国内感染が東京都を中心に発生した．社会におけるデング熱に対する不安の高まりの中で，医療機関においては，発熱等の主訴を呈し受診した患者の中からどのようにデング熱とその他の疾患を鑑別するかに苦慮した． 方法：デング熱疑いとして他院から紹介された，もしくはデング熱が心配で当科外来を直接受診した，3 カ月以内に渡航歴のない患者を“デング熱国内感染疑い”症例と定義した．平成26年8月25日から9月26 日（8 月27 日に厚生労働省が国内感染デング熱症例について第一報を公表）の間で定義を満たす患者47 例を後方視的に検討した．<BR> 結果：47 例のデング熱国内感染疑い症例の中で，最終的にデング熱と診断されたのは9 例（19.1%）であった．デング熱以外の診断として，2 日以内に自然軽快した発熱が10 例，咽頭炎が7 例，上気道炎が5 例，腎盂腎炎が4 例，感染性腸炎が3 例認められ，その他の疾患では腸チフスや急性HIV 感染症，反応性関節炎，亜急性壊死性リンパ節炎等が認められた．デング熱症例では非デング熱症例と比べ，蚊の刺咬歴，流行地域への訪問歴，白血球減少，血小板減少が有意に多かった．また，統計学的に有意でないものの，初診時において，関節痛，筋痛がデング熱症例で多い傾向にあり，皮疹や鼻汁，咽頭痛は非デング熱症例で多い傾向が認められた．検討した47 例には9 例（19.1%）の細菌感染症および，13 例（27.7%，うちデング熱7 例）の入院例が含まれた．<BR> 結論：“デング熱国内感染疑い”症例の多くは，上気道炎や咽頭炎などの日常的に良く遭遇する熱性疾患であったが，中には腎盂腎炎や腸チフスなど菌血症を伴うような重篤な細菌感染症や，全身状態不良で入院の必要な症例も認められた．デング熱症例と非デング熱症例の鑑別には，蚊刺咬歴や流行場所への訪問歴，白血球減少や血小板減少が有用と考えられた．これらの結果を参考にしながら，初期に特異的な症状が乏しい発熱性疾患を丁寧に鑑別し，緊急性のある疾患を除外していくことが肝要である．

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18才女性の重篤蚊刺過敏症により悪性組織球症様病変をきたした1剖検例の報告である. 剖検時, 蚊刺部は陳旧化していたが, 全身諸臓器に組織化学的性質から'低分化組織球'と考えた細胞が白血病様に著しく浸潤していた. 骨髄・リンパ節で'低分化組織球'の増生は軽度であった. '低分化組織球'の組織化学的性状は, peroxidase（－）, AS-DCl法（－）, 種々免疫グロブリン（－）, LC（－）, PNA（＋）, LY（＋）, s-100（－）で, 単球一大食細胞系細胞であることを示していた. 細胞形態学的に貧食能がなく, α-NBEに強陽性であったことから, 単球－大食細胞系の中でも単球側のいわば幼若な組織球にあたると考えられる.本例は蚊刺過敏症による低分化組織球の増殖を証明した最初の報告である.

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We report the case of a young female patient with chronic active Epstein-Barr virus infection (CAEBV) and severe hypersensitivity to mosquito bites (SHMB). She showed a marked increase of NK cell population in peripheral blood. The NK cell population was suggested to be infected with EBV, and to be oligoclonal by Southern blotting using an EBV genome terminal-repeat probe. The NK cells aberrantly expressed CD25, a high affinity receptor for IL-2, and showed an augmented in vitro proliferative response to IL-2. Moreover, they also showed enhanced expression of both Fas-ligand and Bcl-2, and resistance to in vitro Fasinduced apoptotic cell death (Fas-ACD). Taken together, these observations suggested that both the augmentation of proliferative response to IL-2 and the decrease in Fas-ACD may cause NK cell lineage granular lymphocyte proliferative disorder (NK-GLPD) in patients with CAEBV and SHMB.
(Internal Medicine 41: 651-656, 2002)

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This study investigated endogenous mediators involved in mosquito allergy-associated itching in mice. An intradermal injection of an extract of mosquito salivary gland elicited marked scratching in sensitized mice. The 5-lipoxygenase inhibitor zileuton (100 mg/kg), the 5-lipoxygenase activating peptide inhibitor MK-886 (10 mg/kg), and the glucocorticoid betamethasone 17-valerate (3 mg/kg) inhibited the scratching. The scratching was not affected by the cyclooxygenase inhibitors indomethacin and ketoprofen, the TP prostanoid receptor antagonist SQ-29548, the leukotriene B₄ antagonist ONO-4057, the cysteinyl leukotriene antagonist pranlucast, the leukotriene D₄ antagonist MK-571, the platelet-activating factor antagonist CV-3988, the nitric oxide synthase inhibitor N^G-nitro-L-arginine methyl ester, the H₂ histamine-receptor antagonist cimetidine, the H₁ histamine-receptor antagonist terfenadine plus cimetidine, and cypoheptadine that blocks the 5-HT_1/2 serotonin receptors. Zileuton (100 mg/kg) inhibited the increased activity of the cutaneous nerve branch induced by an intradermal injection of the extract, suggesting the peripheral action. Zileuton and MK-886 (10 and 100 μM) did not affect high K⁺-induced increase in intracellular Ca²⁺ concentration in cultured dorsal root ganglion neurons. The results suggest that 5-lipoxygenase metabolite(s) other than leukotriene B₄ and cysteinyl leukotrienes are involved in mosquito allergy-associated itching.

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The human immunodeficiency virus (HIV) epidemic continues to be associated with misconceptions and misinformed opinions, which increase the risk of HIV transmission. Therefore, the present study aimed to identify the determinant factors among different socioeconomic and demographic factors affecting misconceptions about HIV transmission among ever-married women in Bangladesh. Data and necessary information of 9,272 ever-married women were extracted from the Bangladesh Demographic and Health Survey 2011. Three types of misconceptions were considered. Both bivariate and multivariate analyses were used as the statistical tools to determine the factors affecting misconceptions about HIV transmission. The results revealed that misconceptions are more prevalent among women who are older, less educated, have husbands who are less educated, live in rural areas, have poor economic conditions, and have less access to mass media. The respondent's age, education, husband's education, place of residence, wealth index, and exposure to mass media are significantly associated with the misconceptions. Finally, logistic regression analysis identified age, education, place of residence, wealth index, and exposure to mass media as significant predictors. Because socioeconomic factors are the key determinants of misconceptions about HIV transmission, intervention programs should be aimed at HIV prevention via education and awareness programs to reduce misconceptions as important parts of the prevention strategy.

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Composite lymphoma (CL) is defined as the occurrence of two distinct types of lymphoma within the same patient. Most cases of CL involve Hodgkin and non-Hodgkin lymphomas or two distinct types of B-cell lymphomas; true CL is a composite B-cell and T-cell lymphoma, and is rare. We herein report a case involving concurrent extranodal NK/T-cell lymphoma, nasal-type and diffuse large B-cell lymphoma, which has not been previously reported. As the mechanisms and treatments of composite B-cell and T-cell lymphomas are unclear, further studies are required to improve the prognosis.

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Itch is a sensation that provokes a desire to scratch. Mast-cell histamine was thought to be a key itch mediator. However, histamine and mast-cell degranulation were reported not to elicit scratching in animals. It was difficult to investigate the pathophysiology of itching and to evaluate the antipruritic efficacy of chemical agents in the early 1990 s. We showed that hind-paw scratching and biting were elicited by stimulation with pruritogenic agents in mice. Those results demonstrated for the first time that cutaneous itching could be evaluated behaviorally in animals. We established various animal models of pathological itch of the skin (dry skin, mosquito allergy, surfactant-induced pruritus, and herpes zoster) and mucus membranes (pollen allergy). Mast-cell histamine did not play a key role in itching in any animal model examined except for the pollen allergy model. Histamine is not an exclusive itch mediator of mast cells; tryptase and leukotriene B₄ released from mast cells also act as itch mediators. Epidermal keratinocytes release several itch mediators, such as leukotriene B₄, sphingosylphosphorylcholine, thromboxane A₂, nociceptin, nitric oxide, and histamine, which may play important roles in pathological itching. Appropriate animal models of pathological itching are needed for pharmacological evaluation of the antipruritic efficacy of chemical agents.

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We produced a transgenic rodent malaria parasite (Plasmodium berghei) that contained the luciferase gene under a promoter region of elongation factor-1α. These transgenic (TG) parasites expressed luciferase in all stages of their life cycle, as previously reported. However, we were the first to succeed in observing sporozoites as a mass in mouse skin following their deposition by the probing of infective mosquitoes. Our transgenic parasites may have emitted stronger bioluminescence than previous TG parasites. The estimated number of injected sporozoites by mosquitoes was between 34 and 775 (median 80). Since luciferase activity diminished immediately after the death of the parasites, luciferase activity could be an indicator of the existence of live parasites. Our results indicated that sporozoites survived at the probed site for more than 42 hours. We also detected sporozoites in the liver within 15 min of the intravenous injection. Bioluminescence was not observed in the lung, kidney or spleen. We confirmed the observation that the liver was the first organ in which malaria parasites entered and increased in number.

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ナイジェリアのクワラ州において，作業の危険性の農業従事者の生産性へおよぼす影響について自覚的評価に基づいて調べた．多段階無作為抽出法を用いて全160名の回答者を選別した．実証分析のためのピアソンの積率相関係数解析と共に頻度や割合などの記述的統計手法を用いて分析を行った．調査の結果，共通の農業生産物はトウモロコシ，ヤムイモ，キャッサバであった．また，共通して多い作業上の危険は農具による切傷／傷害，蚊刺しに起因するマラリア，および全身性疼痛であり，農具による傷害および全身性疼痛が農業生産性に大きな影響を及ぼしていることが明らかになった．農業従事者の社会-経済学的特徴と自覚されている農業生産性への作業の危険性の影響との間には，ピアソンの積率相関係数を用いた解析においては有意な相関は認められなかった．これらの結果にもとづき，作業（農業）における危険，とくに全身性の疼痛が，農業生産性に負の効果をもたらすと結論する．この研究からは，政府と関係機関が農業従事者に保護具の使用法を訓練する普及員を通して保護具を安価で提供し，農業労働者に保護具の使用を督励することが推奨され，農業従事者自身が良好な健康状態を維持するための健康管理について教育を行うことが公衆衛生関係者には求められる．

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The potency test of Japanese encephalitis (JE) vaccine is routinely carried out by intracerebral challenge of immunized mice using the Nakayama strain of JE virus, however since natural infection is by the peripheral route with a wild strain, one of the authors has reported (Bull. WHO, 43, 553, 1970) a new method by a subcutaneous challenge test on suckling mice. Since the usual route of infection is the result of , the authors developed a new challenge test by the intravenous route.
Suckling mice 9-13 days old were immunized twice intraperitoneally with 0.15ml of different serial dilutions of vaccine on day 1 and 4. A challenge dose of JE virus equal to 500 icLD₅₀ for suckling mice was administered into the tail vein on day 8, when the mice were not more than 20 days old. The JaGAr-01 strain was used for the challenge virus as it had been more recently isolated and is more virulent than the Nakayama strain.
This method should give a more accurate assessment of the effect of vaccine the purpose of which is to protect humans from infection.

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21歳, 男性。平成6年9月ピラニアの捕獲目的でブラジルのマナオスからネグロ川ぞい約300km上流のジャングルに旅行中, 右上腕を蚊のような虫に刺された。虫刺部に発赤・腫脹を生じるようになり, 中心部には硬結がみられ血漿浸出液を伴う瘻孔を認めるようになった。帰国後近医を受診, 抗生物質を処方され腫脹はやや軽減したが, 右腋窩のリンパ節の腫脹がみられるようになり, その後瘻孔より白色半透明の虫体が出入りするのが目撃された。虫体は捕えようとすると素早く瘻孔にもぐりこんだ。患者自身がでてきた虫体の採取に成功し, 虫体を持参のうえ神戸大学付属病院皮膚科を受診。体長約1.5cm, 白色のとっくり状の虫体で同大医動物学教室にて, ヒトヒフバエのニ齢幼虫と同定された。ヒトヒフバエ(症)は日本土着のものではなく, 中南米からの輸入例が全部を占めている。1974年のKageiらの報告以来本邦12例目となる。最近5&acd;10年間に報告が集中しており, ヒトヒフバエが生息する中南米の熱帯雨林地域への旅行者の激増に伴う発生増加が要因と考えられる。

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