Scintigraphy with J001X, a Klebsiella membrane glycolipid, for the early diagnosis of chronic berylliosis: results from an experimental model.

A glycolipid (J001X) isolated from the membrane proteoglycans of a non-pathogenic strain of Klebsiella pneumoniae was developed to bind selectively to macrophages. A scintigraphic technique could thus be developed and applied to an experimental model of lung berylliosis. Six baboons were injected intratracheally with a beryllium metal suspension. Three to 24 months later, they were submitted to both an anatomical and a functional respiratory evaluation. Two baboons were explored at the early stage of alveolitis and four baboons at a more advanced stage characterised by a granulomatous disorder. Scintigraphy was performed using J001X labelled with 99mtechnetium administered as an aerosol. In the six baboons, conventional imaging techniques (chest x ray film, computed tomography scan, gallium scintigraphy), failed to show either any lung abnormality or mediastinal lymph nodes consistent with beryllium disease. In the two recently contaminated baboons, J001X scintigraphy showed a well defined parenchymal fixation facing the contaminated lobe. In the four baboons who were at a more advanced stage of berylliosis, J001X fixation was always focused paratracheally without any significant involvement of the lung parenchyma. The subcarinal and laterotracheal lymph nodes seen at necropsy corresponded to J001X scintigraphic fixations. In conclusion, when compared with conventional techniques such as chest x ray film, computed tomography scan, magnetic resonance imaging, and gallium scintigraphy, J001X scintigraphy has proved its ability to detect occult lesions in experimental berylliosis in baboons. By comparison with gallium scintigraphy, scintigraphy with J001X appears to have superior sensitivity and can be performed in four hours.     

Scintigraphy with J001X, a Klebsiella membrane glycolipid, for the early diagnosis of chronic berylliosis: results from an experimental model.

A glycolipid (J001X) isolated from the membrane proteoglycans of a non-pathogenic strain of Klebsiella pneumoniae was developed to bind selectively to macrophages. A scintigraphic technique could thus be developed and applied to an experimental model of lung berylliosis. Six baboons were injected intratracheally with a beryllium metal suspension. Three to 24 months later, they were submitted to both an anatomical and a functional respiratory evaluation. Two baboons were explored at the early stage of alveolitis and four baboons at a more advanced stage characterised by a granulomatous disorder. Scintigraphy was performed using J001X labelled with 99mtechnetium administered as an aerosol. In the six baboons, conventional imaging techniques (chest x ray film, computed tomography scan, gallium scintigraphy), failed to show either any lung abnormality or mediastinal lymph nodes consistent with beryllium disease. In the two recently contaminated baboons, J001X scintigraphy showed a well defined parenchymal fixation facing the contaminated lobe. In the four baboons who were at a more advanced stage of berylliosis, J001X fixation was always focused paratracheally without any significant involvement of the lung parenchyma. The subcarinal and laterotracheal lymph nodes seen at necropsy corresponded to J001X scintigraphic fixations. In conclusion, when compared with conventional techniques such as chest x ray film, computed tomography scan, magnetic resonance imaging, and gallium scintigraphy, J001X scintigraphy has proved its ability to detect occult lesions in experimental berylliosis in baboons. By comparison with gallium scintigraphy, scintigraphy with J001X appears to have superior sensitivity and can be performed in four hours.     

Mechanisms Underlying the Skin-Gut Cross Talk in the Development of IgE-Mediated Food Allergy

Immune-globulin E (IgE)-mediated food allergy is characterized by a variety of clinical entities within the gastrointestinal tract, skin and lungs, and systemically as anaphylaxis. The default response to food antigens, which is antigen specific immune tolerance, requires exposure to the antigen and is already initiated during pregnancy. After birth, tolerance is mostly acquired in the gut after oral ingestion of dietary proteins, whilst exposure to these same proteins via the skin, especially when it is inflamed and has a disrupted barrier, can lead to allergic sensitization. The crosstalk between the skin and the gut, which is involved in the induction of food allergy, is still incompletely understood. In this review, we will focus on mechanisms underlying allergic sensitization (to food antigens) via the skin, leading to gastrointestinal inflammation, and the development of IgE-mediated food allergy. Better understanding of these processes will eventually help to develop new preventive and therapeutic strategies in children.     

Berylliosis in Italy: a case of "sarcoidosis" under the threshold limit value

BACKGROUND: Berylliosis is caused by a chronic immune reaction to beryllium; in Italy the first case of beryllium exposure-related disease was described in 1935 by Fabroni-Marradi and two additional cases of beryllium disease were subsequently described by Ambrosi and co-workers in 1968. No case has since been recognized using the standardized criteria including immunological testing. OBJECTIVES: To describe a case report of clinically significant berylliosis that occurred in a man exposed to beryllium for ten years in the workplace at concentrations below the permitted threshold limit value. METHODS: The man complained of dyspnoea, dry cough, weakness and weight loss for the past year and was at first diagnosed as suffering from sarcoidosis because of increased angiotensin converting enzyme levels, alteration of hepatic and renal functional indexes, the presence of diffused reticulo-nodular lung abnormalities with high resolution computed tomography that also showed enlarged mediastinal lymph nodes, abnormal lung physiology with reduced diffusion capacity and a bronchial biopsy showing granulomatous lesions. Because of the occupational history immunological testing and high resolution HLA class II typing were performed. RESULTS: The high response to beryllium in the lymphocytes proliferation test and the HLA typing which revealed the presence of the two susceptibility markers HLA-DPGlu69 and HLA-DRPhe47 led to a diagnosis of berylliosis. CONCLUSIONS: The importance is stressed of suspecting a diagnosis of berylliosis in the proper occupational contexts and encouraging the use of immunological tests for diagnosis, and also the need for critical revision of the permitted threshold limit values.     

Interaction of genetic and exposure factors in the prevalence of berylliosis

Prevalence of berylliosis, a lung disorder driven by the activation of beryllium-specific T cells, is associated with a major histocompatibility complex (MHC) class II marker (HLA-DPB1Glu69) and with the type of industrial exposure. We evaluated the interaction between marker and exposure in a beryllium-exposed population in which the prevalence of berylliosis was associated with machining beryllium. The presence of the marker was associated with higher prevalence (HLA-DPB1Glu69-positive machinists 25%; HLA-DPB1Glu69-negative machinists 3.2%, P = 0.05) and predicted berylliosis independent of machining history (odds ratios 11.8 and 10.1). The study shows that in berylliosis the carrier status of a genetic susceptibility factor adds to the effect of process-related risk factors. Am. J. Ind. Med. 32:337–340, 1997. © 1997 Wiley-Liss, Inc.     

Chronic Pulmonary Berylliosis in a Female Chemist

A chronic progressive granulomatous disease of the lungs is described in a female chemist who worked for about two years with a beryllium compound in the manufacture of fluorescent lighting tubes. The level of beryllium in the laboratory atmosphere was found to be 2·7 μg. per cu.m. and in other parts of the factory up to 39·1 μg. per cu.m. were recorded. Symptoms began about two years after she left this work and she died three years later. A diagnosis of chronic pulmonary berylliosis was made, and confirmation was obtained by lung biopsy when early in the course of the disease a large cyst attached to the right middle lobe was removed by thoracotomy. Tests of lung function showed that there was a low arterial saturation at rest and a normal Pco₂ in spite of marked hyperventilation. Both elastance and resistance of the lungs were greater than normal and total work of breathing was six times the normal. Pregnancy was associated with relief of symptoms which persisted for some months after a normal birth. Death occurred about seven years after exposure to beryllium ceased. At necropsy beryllium was detected in the lungs chemically and demonstrated in histological sections by special stains. Microscopic examination of the lung showed conchoidal bodies and doubly refractile crystals and the pathogenesis of these lesions is discussed. It is suggested that there is a sensitivity reaction to beryllium, which is probably combined with protein to form an antigen, and that the breakdown of necrotic foci provokes a further reaction in the lung with the repeated appearance of fresh lesions.     

铍病患者呼吸功能的测定与分析

对12例铍病、19例可疑铍病,以及10例铍接触者进行了肺功能测定及血气分析。结果铍病组RV、RV/TLC升高、VC、FVC、FEV_1/FVC均显著降低,与其他两组比较,差异非常显著(P<0.01。)MMEF、V_(50)/H、V_(25)/H早期已有损害,并随病变的进展而增加。上述三组的DL_(CO)及K_(CO)均低于正常,且有较高的异常检出率,其中尤以K_(CO)值更为敏感。弥散功能的降低可早于胸部X线异常的出现。呼吸功能测定可作为铍作业工人预防性监测和铍病劳动能力鉴定的重要依据。     

Inducing tolerance against antigens through initial contact via the mucous membrane

Mucosal tolerance arises in response to protein antigens that enter through the mucous membranes. This tolerance is unusual in that it becomes systemic and also arises when these antigens subsequently enter the body through the skin or via the bloodstream. Clinical applications of mucosal tolerance are hampered because induction of tolerance does not appear to be possible once systemic sensitisation has taken place. Research into the immunological mechanisms which underlie tolerance induction indicates marked local differences in antigen presentation and the formation of special classes of T lymphocytes which regulate immune reactions. In the future, this knowledge could lead to the application of tolerance in the selective therapeutic down-regulation of immunological diseases such as allergies and autoimmune diseases.     

MMP-2、MMP-9蛋白在肺组织损伤修复中的表达

目的 观察MMP-2和MMP-9在肺组织损伤修复过程中的表达和变化规律，并探讨它们在肺组织损伤修复中作用的分子机制和意义．方法 20只Wister大白鼠．随机分为一个正常组和臭氧攻击损伤后8个时间的实验组，制作大鼠肺损伤模型。免疫组化分析观察各组MMP-2及MMP-9蛋白表达的强度。结果 成功复制大鼠肺组织损伤动物模型；免疫组化分析表明．MMP-2、MMP-9蛋白表达在正常肺组织为弱阳性，在肺组织损伤时，表达上调,且随着肺组织损伤修复行进而先逐渐增强,继而逐渐减弱,当肺组织损伤修复达正常时，MMP-2，MMP-9表达恢复到正常水平。结论 MMP-2、MMP-9的高表达与肺组织损伤密切相关。     

MMP-2mRNA、MMP-9mRNA在肺组织损伤修复中的表达

目的 观察MMP-2mRNA和MMP-9mRNA在肺组织损伤修复过程中的表达和变化规律，探讨它们在肺组织损伤修复中作用的分子机制和意义。方法 20只Wister大白鼠，随机分为一个正常组和臭氧攻击损伤后8个时间的实验组，制作大鼠肺损伤模型。应用RT-PCR技术检测MMP-2、MMP-9基因表达规律。结果 成功复制大鼠肺组织损伤动物模型；RTNR检测结果提示：MMP-2、MMP-9基因在正常肺组织为弱表达，在肺组织损伤时表达下调，损伤修复开始时，表达又上调，且明显高于正常肺组织；当肺组织损伤修复达正常时，MMP-2、MMP-9基因表达水平减弱，接近正常水平。结论 MMP-2mRNA、MMP-9mRNA的低表达与肺组织损伤密切相关。     

Food hypersensitivity in children

Adverse reactions to foods involving abnormal immune reactions to food antigens occur in 2-7% of the North American population; the numbers are perhaps higher in children. Both IgE-mediated and non-IgE-mediated allergic responses occur. IgE-mediated allergic responses to foods are the most dramatic and perhaps the most easily diagnosed type of food allergy. Non-IgE-mediated food hypersensitivity is more chronic, less acute, less obvious in its clinical presentation, and often more difficult to diagnose. It usually presents in infants between one week and three months of age with vomiting and diarrhea, although irritability, poor feeding, and failure to thrive are not uncommon. A thorough history and physical examination are often key in establishing a diagnosis of food protein hypersensitivity. In non-IgE-mediated disease, skin tests and immunological studies are not helpful. Eliminating the food allergen is the only means of dealing with a food allergy in most patients. About 85% of infants who have formula protein intolerance will outgrow their symptoms somewhere between 1 month and 3 years of age, older children and adults are somewhat less likely to lose their sensitivity, although approximately one-third will after 1-2 years of dietary restriction.     

Vitamin E Isoforms as Modulators of Lung Inflammation

Asthma and allergic diseases are complex conditions caused by a combination of genetic and environmental factors. Clinical studies suggest a number of protective dietary factors for asthma, including vitamin E. However, studies of vitamin E in allergy commonly result in seemingly conflicting outcomes. Recent work indicates that allergic inflammation is inhibited by supplementation with the purified natural vitamin E isoform α-tocopherol but elevated by the isoform γ-tocopherol when administered at physiological tissue concentrations. In this review, we discuss opposing regulatory effects of α-tocopherol and γ-tocopherol on allergic lung inflammation in clinical trials and in animal studies. A better understanding of the differential regulation of inflammation by isoforms of vitamin E provides a basis towards the design of clinical studies and diets that would effectively modulate inflammatory pathways in lung disease.     

Dermal testing of vaccines for children at high risk of allergies

Vaccinations for children with allergic diseases often need to be postponed or terminated because of the presumed risk of an immediate-type allergic reaction such as anaphylaxis. A new skin test protocol for predicting allergic reactions using the vaccine itself and the following stepwise vaccination method were developed and tested. Intradermal tests using 1:10 and 1:100 diluted measles vaccine indicated that the former was superior to the latter because a positive reaction against 1:10 diluted vaccine was found in 28.6% of 49 patients with severe allergic diseases including bronchial asthma, atopic dermatitis, food allergies and allergies to two or more allergens with high levels of IgE, as compared with the reaction against 1:100 diluted vaccine in 10.2% of the patients. Patients negative for 1:10 skin tests were safe from the following full-dose vaccine shots. Three patients showed very strong local reactions against measles vaccine, and avoided receiving the following full-dose shot. Positive reactions to skin tests of 1:10 diluted vaccine were found in 11 patients, who were given stepwise vaccinations. Three patients had adverse reactions, and two of them had been negative for 1:100 skin tests. In the case of influenza vaccine, skin tests were again more sensitive to 1:10 than to 1:100 diluted vaccine, because 3 out of 14 patients with positive reactions showed immediate-type adverse reactions against the following stepwise vaccinations, and 1 of them was negative for the 1:100 skin test. Moreover, the results of the skin prick test (undiluted vaccine) and the intradermal skin test (1:10 diluted vaccine) indicated that the latter was more useful in both cases of measles (54 patients) and influenza vaccine (69 patients). Overall, the skin test using 1:10 diluted vaccine was the more suitable for predicting an immediate-type reaction to measles and influenza vaccinations. Patients having negative 1:10 skin tests can be expected to show no adverse reactions to the remaining injections and even the positive subjects will complete the course of vaccine doses by the stepwise method.     

Couriers of asthma: antigenic proteins in natural rubber latex

Natural rubber latex (NRL) is a milky, white liquid containing the polymer cis-1,4-polyisoprene, derived from the laticifer cells of the rubber tree, Hevea brasiliensis. Reports of allergic reactions to NRL, ranging in severity from skin rashes to anaphylaxis and death, have been increasing. High rates of latex allergy are seen in children with spina bifida. Healthcare workers, especially those who frequently use powdered latex medical gloves, can develop NRL allergy and asthma, often resulting in considerable disability. Atopy and, possibly, pre-existing dermatitis predispose to sensitization and allergic symptoms. NRL protein antigens are found in many NRL products and also have been shown to bind to cornstarch glove-donning powders. Of the approximately 240 polypeptides in NRL, nearly 60 are antigenic, and nine have been identified and registered (Hev b 1&ndash9). Many natural latex antigens share epitopes with structural proteins and enzymes from other plant species. Current knowledge indicates that proposed reductions in total glove protein and limitations on the use of powder on NRL gloves are likely to result in a decline in the prevalence and severity of NRL allergies among healthcare workers.     

Survival of BCG in rat tissues

Summary Culture on Löwenstein medium shows that lungs, hilar lymph nodes and spleens from female albino rats injected intravenously with BCG, and then killed after observation periods up to 12 months, contain viable BCG. These organisms induced granulomatous tissue reactions in rat lungs, indicating that the resistance of rats to tubercle bacilli is only relative.     

Food allergy and the potential allergenicity-antigenicity of microparticulated egg and cow's milk proteins

Approximately 3-4 million Americans experience food allergic reactions at some time in their lives. In the pediatric population, eggs and milk are most frequently implicated in food allergic reactions. The most well-understood adverse reactions to foods are secondary to the development of IgE antibodies to specific food antigens. Once an individual becomes sensitized (i.e., makes specific IgE antibodies), ingestion of the food may lead to a variety of cutaneous, respiratory, and/or gastrointestinal symptoms, and anaphylactic shock. The use of SDS-PAGE and immunoblot analyses with sera from documented food allergic patients provide a very sensitive indicator of the antigenic/allergic composition of various foods. As demonstrated in a study of infant formulas of hydrolyzed cow's milk protein, the absence of demonstrable bands on SDS-PAGE gels and immunoblots correlates with an inability to provoke an allergic response. In addition, it was demonstrated that SDS-PAGE with silver staining could detect protein fractions at a concentration of 50-100 ng/ml, a concentration below which allergic individuals are unlikely to react. These studies confirmed that patients clinically allergic to egg and/or cow's milk possess IgE and IgG antibodies to protein fractions in egg and cow's milk, as well as the microparticulated egg/cow's milk proteins, Simplesse and Beta IL. Compared to egg and cow's milk, there is no evidence that the Simplesse or Beta IL test materials possess any "novel" protein fractions or antigens. In addition, there is no evidence that these microparticulated proteins result in increased immunologic activity, as determined by the intensity of protein band staining.(ABSTRACT TRUNCATED AT 250 WORDS)     

黄芩甙—锌配合物抗变态反应的研究

<正> 中药黄芩有效成分黄芩甙(Baicalin)具有消炎、抗菌、利尿、利胆、解热、降压和镇静作用。日本学者江田昭英等先后发现,黄苓甙对致敏豚鼠肺组织释放的慢反应物质(SRS—A)及组胺有明显的抑制作     

视黄酸对大鼠哮喘模型多种炎性因子的影响

目的探讨吸入视黄酸(RA)对急性发作期和慢性持续期哮喘大鼠多种炎症因子影响和作用机制。方法以鸡卵清蛋白(OVA)激发大鼠7d或30 d以制备急性或慢性哮喘模型。在1-7 d或23-30 d期间分别用10μg/ml RA(RA组)、10μg RA+5μg/ml budesonide(RA+BU组)、石蜡油(PO组)雾化吸入治疗1周。急性模型7 d后取血清与肺脏进行检测,慢性模型30 d及随后休息10 d取上清与肺脏进行检测。用免疫荧光、ELISA法检查肺间质细胞因子与血Th因子表达。结果急性发作期PO组胸腺基质淋巴细胞生成素(TSLP)、核因子-κB(NF-κB)、干细胞因子(SCF)表达增加。RA能下调TSLP,但SCF明显上调。慢性持续期PO组TSLP、NF-κB、SCF、IL-4随时间逐步上调,肺感染病灶多,肺泡隔中度增宽。RA组主要炎症因子水平逐渐降低,其中TSLP、IL-4、SCF减少具统计学差异;肺感染病灶少,肺泡隔增宽较轻。BU+RA组下调TSLP表达,但SCF持续上调,肺泡出血与感染较重。结论 RA通过活化巨噬细胞,短暂加重急性发作期哮喘过敏反应,但抑制慢性持续期哮喘肺间质过敏炎症,具免疫调整和抗感染作用。     

铍病免疫的实验研究之一——家兔染尘试验

本实验采用雄性健康家兔18只,分成两个实验组和1个对照组,每组6只。实验组家兔分别每月气管注入氧化铍8mg/kg、16mg/kg,连续两次;对照组注入生理盐水。结果两个实验组分别在染毒后4个月、3个月均形成了肺部肉芽肿病变。实验发现,免疫指标与X线表现及病理改变之间存在着一定的关系。免疫指标阳性反应在某种程度上能反映出病理组织学改变。给临床诊断铍病提供了部分实验依据。     

Scanning electron microscopical investigations of broncho-alveolar casts after intratracheal asbestos fibre instillation

The evaluation of the toxicity of mineral fibres has been tried to achieve in experimental animal models. However, the appearance of fibres in the pleural space could not be explained satisfactorily. Histomorphological examinations showed that intratracheal instillation of asbestos fibres leads to parabronchial and intraalveolar granulomatous tissue reactions and bronchial epithelial regenerations. For further elucidation of the pathogenesis of lung cancer and of mesothelioma the localisation and transport of inhaled fibres is of high interest. Thus, a three dimensional visualization of the structure of rat lungs before and after intratracheal instillation of UICC crocidolite fibres was performed by plastic casts to follow the way of asbestos fibres in the lung tissues and the pleura. The casts allowed to demonstrate airway structures with imprints of epithelial cells and blood vessels of normal and treated animals by scanning electron microscopy. Instilled asbestos fibres transformed bronchial structures and resulted in cystic deformations of the pleural surface. The penetration of single fibres through bronchial trunks and the visceral pleura could be shown for the first time in a three-dimensional topography of the affected tissue. Now, there is support for similar results of histomorphological examinations indicating the possibility that asbestos fibres could penetrate the pleura and migrate into the pleural space. The question if the migration of fibres is a mechanical movement or an active transport is still under discussion.