Kunmei Ji

Anaphylactic shock caused by silkworm pupa consumption in China

mugwort sensitization. Although a double-blind placebo-controlled food challenge is the gold standard for the diagnosis of a food allergy (6), open oral challenge was our best viable option in this study. In conclusion, we report a case of severe anaphylactoid reaction caused by C. lanceolata root ingestion in a patient with allergic rhinitis. This reaction was not mediated by IgE, but rather by direct histamine releasing effects via basophils. This study was supported by a grant from the Korean Health 21 R&D Project of the Ministry of Health & Welfare, Republic of Korea (A030001).

Comments on serious anaphylaxis caused by nine Chinese herbal injections used to treat common colds and upper respiratory tract infections.

Abstract Reports describing severe allergic shock and fatality following treatment of a common cold or upper respiratory tract infection (URTI) with a Chinese herbal injection were collected. Our analysis of the risks associated with this treatment suggested that the potential risk of serious, or even lethal, anaphylaxis should preclude its use in treating common colds and URTIs. In light of our findings herein, we propose the following five suggestions for improving the clinical safety of delivering Chinese herbal injections as medical treatments. First, Chinese herbal injections should not be delivered in the clinic to treat patients in accordance with Bian zheng lun zhi (broad-spectrum application based on holistic Traditional Chinese Medicine (TCM) theory and methodology), but rather they should be administered to target specific indicated disease processes. Second, Chinese herbal injection indications should be based on the results of double-blind randomized controlled clinical trials. Third, Chinese herbal injections should be used only in cases involving severe disease or to rescue patients in critical condition; they should not be used to treat mild, relatively innocuous diseases, such as common colds and upper respiratory tract infections, given the risk of doing harm. Fourth, Chinese herbal injection formulas should include materials from only a single or a small number of plant sources in known quantities. Fifth, more studies examining the toxicology and allergenic potential of Chinese herbal injections are needed.

Conservative Management of Pediatric Nephrolithiasis Caused by Melamine-Contaminated Milk Powder

OBJECTIVE. In this article we report our experience with the diagnostic screening and management of children with melamine-induced nephrolithiasis. METHODS. A total of 1091 children younger than 4 years who had been exposed to melamine-contaminated formula from September 17 to October 12, 2008, were screened for nephrolithiasis at the department of pediatrics at Shenzhen Nanshan Hospital in China. During the clinical examination, each patients demographic characteristics were recorded together with the details of his or her milk-consumption profile during the contamination scare and any clinical signs of poisoning. Urinary stones were detected by B-ultrasonography, and renal status was examined by a routine urine test panel and a renal function test. When urinary stones were detected, patients were ordered to cease consumption of the suspected formula, and a conservative treatment course was adopted, including infusion of fluids, urinary alkalinization, increased water consumption, and diuresis. RESULTS. Of the 1091 children screened, 12 (1.1%) were diagnosed with kidney stones. They had been exposed to the contaminated milk from 1 to 24 months. Eleven (91.7%) of these 12 patients had consumed milk with a high level of melamine content (955–2563 ppm); 1 patient (8.3%) had consumed milk with a low-level melamine content (6.2–17.0 ppm). Six patients exhibited dysuria; the remaining 6 patients were asymptomatic. All 12 patients had normal renal function, although 4 had proteinuria, and 1 had hematuria. The kidney stones were resolved within 3 to 5 days of commencing treatment in all 12 cases. CONCLUSIONS. Nephrolithiasis was associated with high melamine-exposure levels. A combination of B-ultrasonography and urinalysis is suitable for screening for pediatric nephrolithiasis caused by melamine poisoning. The condition can be resolved with a conservative treatment approach in patients without serious clinical symptoms who have normal kidney function.

Anaphylactic shock and lethal anaphylaxis caused by food consumption in China

A review of case reports of anaphylactic shock and lethal anaphylaxis caused by food consumption occurring in China was conducted. Case reports published in Chinese medical journals from 1980 to 2007 were considered in the review. According to these reports, the most common allergenic offenders were pineapple, soft-shelled turtle and crab.

Detection of Dermatophagoides farinae in the dust of air conditioning filters.

Background: The allergenic dust mite species Dermatophagoides pteronyssinus and Dermatophagoides farinae generally inhabit warm moist environments. This study tested the hypothesis that these allergenic species may thrive in air conditioner filters. Methods: A year-long investigation of the dust mite population densities and species identities living in air conditioner filters in Shenzhen City in Southern China was performed. Additional data describing the levels of major dust mite allergen proteins from samples collected in July and August 2004 were analyzed. Genetic polymorphism analysis of Der f 1 and Der f 2 genes in the collected animals was also conducted. Results: Our investigation revealed that larval dust mites started to grow in March, from which time their populations proceeded to steadily increase until reaching their population zenith in July and August. The dust mite populations decreased sharply in October and live dust mites were no longer observed in the winter. Among the mites collected in July and August, 30.1 and 25.8% were of the species D. farinae. The concentration of Der f 1 was 3.04 ± 1.75 and 3.21 ± 1.84 µg/g dust in July and August, respectively, and that of Der f 2 was 2.15 ± 0.82 and 2.04 ± 1.15 µg/g dust. Four types of Der f 1 and 5 types of Der f 2 cDNA sequences were cloned from collected Der f mites. Their sequences were highly homologous with those previously published in GenBank (No. AB034946.1 and No. AB195580.1). Conclusions: This research demonstrated that Der f allergens exist in the dust of air conditioner filters in this area.

A Cytokine–Cytokine Interaction in the Assembly of Higher-Order Structure and Activation of the Interleukine-3:Receptor Complex

Interleukine-3 (IL-3) binds its receptor and initiates a cascade of signaling processes that regulate the proliferation and differentiation of hematopoietic cells. To understand the detailed mechanisms of IL-3 induced receptor activation, we generated a homology model of the IL-3:receptor complex based on the closely related crystal structure of the GM-CSF:receptor complex. Model-predicted interactions between IL-3 and its receptor are in excellent agreement with mutagenesis data, which validate the model and establish a detailed view of IL-3:receptor interaction. The homology structure reveals an IL-3:IL-3 interaction interface in a higher-order complex modeled after the dodecamer of the GM-CSF:receptor complex wherein an analogous GM-CSF:GM-CSF interface is also identified. This interface is mediated by a proline-rich hydrophobic motif (PPLPLL) of the AA′ loop that is highly exposed in the structure of isolated IL-3. Various experimental data suggest that this motif is required for IL-3 function through receptor-binding independent mechanisms. These observations are consistent with structure-function studies of the GM-CSF:receptor complex showing that formation of the higher-order cytokine:receptor complex is required for signaling. However, a key question not answered from previous studies is how cytokine binding facilitates the assembly of the higher-order complex. Our studies here reveal a potential cytokine–cytokine interaction that participates in the assembly of the dodecamer complex, thus linking cytokine binding to receptor activation.

Sublingual immunotherapy efficacy of Dermatophagoides farinae vaccine in a murine asthma model.

Background: Allergen-specific sublingual immunotherapy is a potential treatment for allergic diseases. Its effective dose and underlying mechanism are still to be explored. Here, we investigated the efficacy and mechanism of sublingually administered Dermatophagoides farinae (Der f) vaccine in a murine asthma model. Methods: BALB/c mice were sensitized intraperitoneally with Der f extract absorbed to alum, followed by sublingual treatment with Der f vaccine for 6 weeks. The mice were subsequently challenged intranasally with Der f extract for 1 week. We analyzed their clinical symptoms, antibody levels, cytokine levels, T-cell proliferation and the regulatory T-cell numbers. Results: Mice treated with high-dose Der f sublingual vaccine prior to challenge displayed alleviated symptoms such as airway hyperreactivity, lung inflammation and mucus production, as well as less eosinophilic cells in bronchoalveolar lavage fluid. Interestingly, reduced responses of Der-f-specific IgE and increased responses of Der-f-specific IgA and IgG1 were aroused in the high-dose Der f sublingual vaccine group. We also observed that interleukin-4 was reduced and interferon-γ and interleukin-10 were increased among splenocytes and in bronchoalveolar lavage fluid, which inhibited Der-f-specific T-cell proliferation of the spleen and increased CD4+CD25+Foxp3+regulatory T cells in the spleen. However, mice treated with low-dose Der f sublingual vaccine developed allergic asthma. Conclusion: Our results illustrate that high-doseDer f sublingual vaccine may play a role in immunologic protection in murine allergic asthma, possibly by inducing regulatory T cells and Th1 reaction.

Anaphylactic shock and lethal anaphylaxis caused by Houttuynia Cordata injection, a herbal treatment in China

Houttuynia Cordata injection (HCI) is the administration of a herbal extract of sterile volatile oils from distillation of fresh H. Cordata with a milliliter equivalent to 2 g of herbal materials(1). It was widely used in China to treat various diseases because of its antibiotic, antiviral, anti-inflammatory and immunityimproving effects (1).Houttuynia Cordata injection was estimated to have been used 280 million times in China in 2005 (1). This extensive herbal treatment is accompanied by a substantial incidence of life threatening anaphylaxis (1). We analyzed 30 articles describing cases of anaphylactic shock and lethal anaphylaxis caused by HCI. The articles were collected from medical journals published in China from 1980 to 2007. Collectively, they report 39 episodes of anaphylactic shock and five deaths (2–6). Four of the five lethal anaphylaxis incidences occurred following intravenous injection (IVI) and one following intramuscular injection (IMI). The patients ages ranged from 5 to 57 years (Table 1) (2–6). They were hospitalized for upper respiratory tract infection (URTI, n = 3), bronchitis (n = 1) and chronic eczema (n = 1) (2–6). When allergic reactions to HCI occurred, epinephrine was injected immediately; however, it failed to save their lives (2–6). The interval between HCI and the time of death ranged from 0.25 to 72 h (2–6). Among the 39 anaphylactic shock cases, eight (20.5%) patients were given an IMI and 31 (79.5%) were given an IVI. Their ages ranged from 2.4 to 75 years. They were seeking treatment for URTI (n = 19), acute bronchitis (n = 7), tonsillitis (n = 7), acute gastroenteritis (n = 2), pneumonia (n = 1), acute pelvic inflammatory disease (n = 1), otitis media (n = 1) and chickenpox (n = 1). Abnormalities were noticed from several seconds to 20 min post-HCI. Among the patients who suffered anaphylactic shock, a 12-year-old girl with an URTI had no reaction following one IMI, but then presented with anaphylactic shock just 15 min after receiving a second injection. In another case, a 12-year-old boy with an URTI showed no allergic reaction after two IMIs, but then presented with anaphylactic shock just 5 min after receiving a third injection. A 26-year-old pregnant woman at 29 weeks gestation with an URTI and no history of drug allergies presented with anaphylactic shock just 5 min after HCI. Likewise, a 22-year-old Iranian woman with no history of drug allergies was seeking treatment for an URTI when she suffered severe anaphylactic shock just 2 min after receiving intravenous HCI. She was rescued by epinephrine within 10 min and was the first known foreign victim of HCI-induced anaphylaxis in China. All 39 patients were rescued without sequelae. The instability of houttuyfonate, a major active ingredient in HCI, may underlie HCI hypersensitivity (1). The human metabolism patterns of numerous other potentially allergenic constituents Severe allergic shock and fatality caused by the herbal treatment with Houttuynia Cordata injection.

Quikgene: A gene synthesis method integrated with ligation-free cloning

Gene synthesis is a convenient tool that is widely used to make genes for a variety of purposes. All current protocols essentially take inside-out approaches to assemble complete genes using DNA oligonucleotides or intermediate fragments. Here we present an efficient method that integrates gene synthesis and cloning into one step. Our method, which is evolved from QuikChange mutagenesis, can modify, extend, or even de novo synthesize relatively large genes. The genes are inserted directly into vectors without ligations or subcloning. We de novo synthesized a 600-bp gene through multiple steps of polymerase chain reaction (PCR) directly into a bacterial expression vector. This outside-in gene synthesis method is called Quikgene. Furthermore, we have defined an overlap region of a minimum of nine nucleotides in insertion primers that is sufficient enough to circularize PCR products for efficient transformation, allowing one to significantly reduce the lengths of primers. Taken together, our protocol greatly extends the current length limit for QuikChange insertion. More importantly, it combines gene synthesis and cloning into one step. It has potential applications for high-throughput structural genomics.

Monoclonal antibodies against recombinant Der f 3 reveal localization of Der f 3 in the gut and faecal pellets of Dermatophagoides farinae

Home dust mite derived materials are known to be a major source of problematic inhalant allergens. The aim of this study was to determine the localization of the group 3 allergen, Der f 3, within Dermatophagoides farinae, in order to assess the relative importance of excreted materials and nonexcreted body components as allergen sources. Recombinant Der f 3 (rDer f 3) was expressed in bacteria and purified as an immunogen for production of monoclonal antibodies (mAb) against it. Dermatophagoides farinae mites and their faecal pellets were embedded in paraffin, and serial sections were immunoprobed with mAb clone 3D3 against Der f 3. D. farinae midgut mucosa, gut contents and faecal pellets were strongly immunopositive for Der f 3. Der f 3 immunoreactive products were not detected in any other internal organs of the mite. These results suggest that Der f 3 allergen may be synthesized in and secreted from the digestive tract and excreted from the mite’s body in the faecal pellets.