bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased interleukin‐10 and macrophage inflammatoryprotein‐1α release from blood monocytes ex vivo duringlate‐phase response to allergen in asthma
Authors: Lim S. , John M. , Seybold J. , Taylor D. , Witt C. , Barnes P. J. , Chung K. F.
Published: March 2003

Background:We determined the effect of late‐phase responses to allergen challenge of mildly allergic asthmatic patients on the expression and release of the cytokines IL‐10 and MIP‐1α from peripheral blood monocytes.

Methods:Sixteen mildly allergic asthmatics were exposed to increasing concentrations of allergen aerosol. Nine demonstrated an early response alone (single responders), while seven had an early followed by a late response (dual responders). Monocytes were isolated from venous blood before and 24 h after allergen challenge, and placed in short‐term culture for determination ofIL‐10 mRNA expression by reverse‐transcription polymerase chain reactionand protein release. MIP‐1α protein release was measured byradioimmunoassay.

Results:IL‐10 mRNA expression was significantly higher in dual responders than early responders alone, for unstimulated monocytes or for monocytes exposed to lipopolysaccharide or IL‐1β. In addition, the release of IL‐10 and MIP‐1α from monocytes of dual responders was also enhanced.

Conclusions:Circulating monocytes are primed to release more of the cytokines, IL‐10 and MIP‐1α, in dual but not in single responders, at 24 h afterallergen. They may contribute to allergen‐induced inflammatory responsesin the airways.
Asthma, skin symptoms, and allergy in a condom factory
Authors: Rask‐Andersen A. , Boman J. , Grängsjö A. , Silverdal M. , Lindberg M. , Lundberg M. , Svensson L.
Published: March 2003

Background:Cases of occupational asthma have been reported in condom factories in the UK and France, but there has been no epidemiologic studyof groups of workers in such factories. This investigation aimed to study the prevalence of symptoms in a Swedish condom factory, to determine groupsat special risk, and to suggest preventive measures.

Methods:A questionnaire was mailed to 35 employees, 29 women and six men with mean ages of 37 and 32 years, respectively. All subjects were interviewed by a physician and underwent skin prick test with latex and epicutaneous testing with 39 substances, and blood samples were taken for allergy testing.

Results:Phadiatop® was positive in 23%, RAST against Lycopodium in 31%,and RAST against latex in one of these 11. Ten subjects (29%) had work‐related nose/eye symptoms; of these, eight had positive RAST to Lycopodium; three also had symptoms of occupational asthma and contact urticaria. Only one had positive RAST to latex. Five of the nine subjects with positive Phadiatop also had positive RAST to Lycopodium. All those with RAST positive to Lycopodium had worked in packaging, the area of the factory with the greatest exposure. The results of the patch tests did not correlate with the work‐related symptoms.

Conclusions:In a Swedish condom factory, there were a high prevalence of rhinoconjunctivitis and a small number of cases of asthma and contact urticaria caused by allergy to Lycopodium.
Arachidonic acid metabolism in inflammatory cells of patients with bronchial asthma
Authors: Calabrese C. , Triggiani M. , Marone G. , Mazzarella G.
Published: March 2003

Over the last few years, the demonstration of beneficial effects of leukotriene receptor antagonists in various forms of asthma has renewed clinical and pharmacologic interest in this class of lipid mediators. Several studies demonstrated an increased biosynthesis of cysteinyl leukotrienes (CysLT) in asthmatic patients. However, the reasons for the dysregulated production of CysLTs in asthmatic patients are not completely defined. An improved method of lipid mediator detection and the availability of cells isolated from human airways (by bronchoalveolar lavage [BAL] and bronchial biopsies) have allowed initial studies to address this issue. Eosinophils retrieved from inflamed airways of asthmatics have a larger arachidonic acid (AA) content than their blood counterpart. The high level of AA in these cells is primarily due to a remodeling of endogenous arachidonate pools with the accumulation of this fatty acid in a triglyceride‐associated pool. In addition, elevated levels of a secretory form of phospholipase A2, the key enzyme initiating the cascade of CysLTs, are found in the BAL of asthmatics. Finally, eosinophils isolated from the BAL of asthmatics have an increased expression of LTC4 synthase. The level of expression of this enzyme correlates with the increased amount of CysLTs produced in the airways of these patients. Taken together, these data identify at least two possible mechanisms to explain the excessive CysLT production in asthmatics:

an increased content of AA in the glycerolipid pools of inflammatory cells

an enhanced activity of key biosynthetic enzymes involved in CysLT synthesis.
Comparison of allergen‐induced changes in bronchial hyperresponsiveness and airway inflammation between mildly allergic asthma patients and allergic rhinitis patients
Authors: Alvarez M. J. , Olaguibel J. M. , Garcia B. E. , Tabar A. I. , Urbiola E.
Published: March 2003

Bronchial eosinophilic inflammation and bronchial hyperresponsiveness (BHR) are the main features of allergic asthma (AA), but they have also been demonstrated in allergic rhinitis (AR), suggesting a continuity between both diseases. In spite of not fully reproducing natural allergenic exposure, the allergen bronchial provocation test (A‐BPT) has provided important knowledge of the pathophysiology of AA. Our aim was to verify the existence of a behavior of AA and AR airways different from the allergen bronchial challenge‐induced airway eosinophilic inflammation and BHR changes. We studied a group of 31 mild and short‐evolution AA and 15 AR patients, sensitized to Dermatophagoides pteronyssinus. The A‐BPT was performed with a partially biologically standardized D. pteronyssinus extract, and known quantities of Der p 1 were inhaled. Peripheral blood (eosinophils and ECP) and induced sputum (percentage cell counts, ECP, albumin, tryptase, and interleukin [IL]‐5) were analyzed, before and 24 h after A‐BPT. Methacholine BHR, assessed before and 32 h after the A‐BPT, was defined by M‐PD20 values and, when possible, by maximal response plateau (MRP). The A‐BPT was well tolerated by all the patients. AA presented a lower Der p 1 PD20 and a higher occurrence of late‐phase responses (LPR). M‐PD20 values decreased in AA, but not in AR, patients. MRP values increased in both groups. Eosinophils numbers and ECP levels increased in blood and sputum from both AA and AR, but only the absolute increment of sputum ECP levels was higher in AA than AR patients (P=0.025). The A‐BPT induced no change in sputum albumin, tryptase, or IL‐5 values. We conclude as follows:

In spite of presenting a lower degree of bronchial sensitivity to allergen, AR patients responded to allergen inhalation with an eosinophilic inflammation enhancement very similar to that observed among AA.

MRP levels increased in both AA and AR patients after allergen challenge; however, M‐PD20 values significantly changed only in the AA group, suggesting that the components of the airway response to methacholine were controlled by different mechanisms.

It is possible that the differences between AR and AA lie only in the quantitative bronchial response to allergen inhalation.
The association between atopy and asthma in a semirural area of Tanzania (East Africa)
Authors: Sunyer J. , Torregrosa J. , Anto J. M. , Menendez C. , Acosta C. , Schellenberg D. , Alonso P. L. , Acosta C. , Schellenberg D. , Kahigwa E. , Kahigwa E.
Published: March 2003

Background: Atopy is consistently associated with asthma, except in a study in Africa. We assessed the association between atopy and asthma in women from a semirural area of Tanzania (East Africa).

Methods: All pregnant women delivering at the district hospital during a 1‐year period were recruited (n=658, 60.6% of those selected). Asthma was investigated by a standard questionnaire and atopy by specific IgE (immunoglobulin E) antibodies to Dermatophagoides pteronyssinus (Der p 1) and cockroach.

Results: The prevalence of wheezing chest was 10.7%; of asthma, 3.5%. Levels of specific IgE of >0.35 kU/l (73%) and high levels of total IgE (62% higher than 1000 kU/l) were highly prevalent. Specific IgE antibody levels in sera were not associated with asthma (3.8% of women with negative specific IgE to any antigen had asthma in comparison to 4.0% of women with positive specific IgE; odds ratio [OR]=1.06, 0.35–3.22). Total IgE was not different between women with asthma and women without asthma (P=0.36).

Conclusions: In tropical regions, the association between allergy and asthma is complex, and specific IgE reactivity to environmental allergens may not be related to asthma.
Food anaphylaxis in schools: evaluation of the management plan and the efficiency of the emergency kit
Authors: Moneret‐Vautrin D. A. , Kanny G. , Morisset M. , Flabbee J. , Guénard L. , Beaudouin E. , Parisot L.
Published: March 2003

Background: Children with severe food allergies can benefit from a personalized care project (PCP) in schools. The usefulness of the PCP and the residual risk of allergic emergencies are poorly appreciated. The objective was to evaluate the efficiency of the management plan and the training in the use of the emergency kit.

Methods: A telephone survey using a detailed questionnaire was performed in 45 families whose children had been previously referred to the department. The distribution of disorders was as follows: asthma, 37.7%; atopic dermatitis and asthma, 28.8%; atopic dermatitis, 15.5%; angioedema and urticaria, 13.3%; and anaphylactic shock, 4.2%. Food allergy had been diagnosed in the 45 children by past history, and double‐blind or single‐blind, placebo‐controlled food challenges (DBPCFCs, or SBPCFCs) with evidence of specific IgE. Exactly 75.5% of the children had peanut allergy. Multiple food allergies characterized 46.8% of the subjects. They had benefited from a strict elimination diet and a protocol for emergency care including a ready‐to‐use intramuscular epinephrine injection. A PCP had been requested by the School Public Health Service.

Results: Thirty‐nine PCPs were implemented (86.5% of the requests). They represented 63% of the PCPs for food allergy in the eastern region of France: one per 5800 school‐age children. The retrospective period of evaluation was 25 months on average. The types of meals were very diverse, and medically acceptable in 83% of cases. The place where the emergency kit was stored in the school varied. Forty reactions occurred in 33% of the children (5/6 times in the absence of a PCP), asthma in 28%, shock in 1%, and immediate skin reactions in 11%. Reactions occurred at home in 78% of the subjects, and in school in 22% of the subjects. The cause of the reactions was not specifically known in 63% of cases. Twenty‐seven percent of the reactions were linked to the ingestion of food allergens. In 10% of subjects, the reaction was due to a modification of ingredients by the food industry.

Conclusions: The frequency of respiratory symptoms during oral challenge tests was confirmed by the frequency of asthmatic reactions within the follow‐up period. The role of hidden allergens and of misleading labeling validates the need for PCPs in the case of peanut and tree nut allergies, past history of severe reactions, multiple food allergies, reactions to a low dose in DBPCFCs, and asthmatic reactions to foods. This study provides encouraging data on the usefulness of PCPs and confirms the need for thorough instruction and training of the school staff in dealing with allergic emergencies. Addition of a β‐agonist spray to the emergency kit is suggested.
Involvement of urban living environments in atopy and enhanced eosinophil activity: potential risk factors of airway allergic symptoms
Authors: Kuwahara Y. , Kondoh J. , Azuma E. , Nakajima T. , Hashimoto M. , Tatara K. , Komachi Y.
Published: March 2003

Background: Airway allergic diseases, such as bronchial asthma and allergic rhinitis, have increased, especially in urban areas. These diseases are characterized by airway inflammation with enhanced eosinophil activity, and the risk of disease development has been shown to increase with the prevalence of atopy.

Methods: Questionnaires were administered to 426 healthy adult women aged 30–74 years, living in an urban area of Osaka, Japan, to survey individual living environments and airway allergic symptoms such as cough, sputum, and wheezing. Moreover, serum house‐dust‐mite (Dermatophagoides pteronyssinus, [Der p])‐specific immunoglobulin E (IgE) and serum eosinophil cationic protein (ECP) were examined by radioimmunoassay, and the atopic status (atopic sensitization) and enhanced eosinophil activity were assessed as Der p‐specific IgE RAST scores of 2–6 and ECP levels of more than 10 ng/ml, respectively.

Results: Intensive use of electric air conditioners in hot weather (odds ratio: 2.07 [95% CI: 1.11–3.87]) and mold proliferation in the kitchen (2.77 [1.34–5.73]) significantly increased the risk of atopic sensitization. Poor home ventilation and family smoking appeared to be positively but not significantly associated with atopic sensitization. Personal smoking and intensive use of the air conditioner appeared to be positively related to enhanced eosinophil activity. Atopic status showed significant involvement in the development of wheezing, and the development of cough was significantly associated with enhanced eosinophil activity.

Conclusions: The results suggest that some urban styles of living are involved in atopic sensitization and enhanced eosinophil activity in the Japanese urban population, probably due to living conditions, such as indoor dampness and poor home ventilation, caused by tight insulation, which increase exposure to indoor air pollutants, such as respirable mite allergens and tobacco smoke.
The prevalence of allergy to egg: a population‐based study in young children
Authors: Eggesbø M. , Botten G. , Halvorsen R. , Magnus P.
Published: March 2003

Background: The aim of the present study was to estimate the prevalence of adverse reactions to egg, as population‐based prevalence estimates based on objective diagnostic procedures are lacking.

Methods: The parents of 2721 children in a population‐based birth cohort completed questionnaires on the occurrence of any reaction to food at 12, 18, and 24 months of age. Children with parentally reported reactions to eggs at the age of 2 years were selected for further examination. A stepwise diagnostic procedure was developed that included diet trials at home, skin prick tests, and open and double‐blind, placebo‐controlled food challenges. The mean age of the children at the time of the examination was 2.5 years (CI 2.5–2.6). A sample of children without perceived reactions to egg was also selected for assessment of unrecognized reactions.

Results: The estimated point prevalence of allergy to egg in children aged 2½ years was 1.6% (CI 1.3–2.0%), with an upper estimate of the cumulative incidence by this age calculated roughly at 2.6% (CI 1.6–3.6). Almost all reactions were IgE mediated. In general, two‐thirds of the parentally perceived reactions were verified. However, the positive predictive value of a parentally perceived reaction depended on the number of times it had been reported, and increased from 50% to 100%, for reactions reported one and three times, respectively. Unrecognized reactions were infrequent.

Conclusions: This study confirms that allergy to egg is frequent in a child population.
Occupational asthma caused by exposure to cyanoacrylate
Authors: Quirce S. , Baeza M. L. , Tornero P. , Blasco A. , Barranco R. , Sastre J.
Published: March 2003

Background: Exposure to acrylates may give rise to rhinitis and asthma in both industrial and domestic environments. The mechanisms underlying these respiratory conditions caused by acrylates remain largely unknown.

Methods: We studied two assembly operators exposed to cyanoacrylate glue who developed rhinitis and asthma symptoms. The causal relationship of these symptoms to cyanoacrylate glue exposure was investigated by serial peak expiratory flow (PEF) monitoring at work and off work. Moreover, inhalation testing was performed by asking the patients to mimic exposure at work with the cyanoacrylate glue in a 7‐m3 challenge chamber.

Results: Serial PEF monitoring at work and away from work was consistent with occupational asthma in both patients. The methacholine inhalation test was negative in patient 1 (off work) and showed bronchial hyperresponsiveness in patient 2. After 20‐min exposure to cyanoacrylate, the patients had late and progressive asthmatic reactions, respectively, and the methacholine test became positive in patient 1. Induced‐sputum samples obtained 3 and 24 h after the cyanoacrylate challenge showed a marked increase in sputum eosinophils.

Conclusions: Exposure to cyanoacrylate in these patients provoked not only variable airflow limitation and bronchial hyperresponsiveness, but also pronounced eosinophilia in sputum.
Diagnostic evaluation of grass‐ and birch‐allergic patients with oral allergy syndrome
Authors: Anhoej C. , Backer V. , Nolte H.
Published: March 2003

Background: Patients with birch and grass allergy often suffer from oral allergy symptoms when ingesting cross‐reacting fresh fruits and vegetables. However, fruit and vegetable allergen extracts are often readily degradable or contain clinically irrelevant cross‐reacting epitopes, resulting in diagnostic discrepancies when fruit and vegetable allergic reactions are evaluated. The risk of using nonstandardized fresh food extracts for skin testing may also be of concern.

The objective was to compare and evaluate the clinical utility of selected recombinant grass and birch cross‐reacting food allergens with fresh and commercial melon, hazelnut, and apple extracts.

Methods: Thirty‐six grass‐ and or birch‐allergic patients and 17 control subjects consented to participate in the study. All subjects were skin prick tested and had basophil histamine‐release tests done with fresh fruits and various extracts of hazelnut, apple, and melon. The diagnosis of oral allergy syndrome was confirmed by oral challenges. In addition, histamine release to recombinant Bet v 1 and Bet v 2, and recombinant Phl p 1 and Phl p 2, Phl p 5 was performed.

Results: The skin prick test with fresh hazelnut, apple, and melon showed sensitivities of 0.97, 0.92, and 0.89, respectively. The corresponding specificities were 0.78, 0.72, and 0.82, respectively. In contrast, the histamine‐release test with hazelnut, apple, and melon gave sensitivities of 0.87, 0.71, and 1.00, respectively. The corresponding specificities were 0.65, 0.93, and 0.43. The skin prick test showed excellent negative predictive value (>90%). No added value of recombinant allergen testing was noted. Oral challenge did not result in severe systemic reactions, and no systemic reactions were observed with skin prick tests with fresh fruits.

Conclusions: The skin prick test showed an almost optimal diagnostic value with a satisfactory sensitivity (>89%) and excellent negative predictive value with fresh fruits. When the skin prick test with fresh nut and apple cannot be performed, histamine release is a diagnostic alternative. Histamine release with melon showed lack of specificity. This was probably due to extensive IgE cross‐reactivity with pollen, since these patients also responded to recombinant Phl p 1 and Bet v 1. Skin testing and challenges with fresh fruits were safe.
Dispersion of horse allergen in the ambient air, detected with sandwich ELISA
Authors: Emenius G. , Larsson P. H. , Wickman M. , Härfast B.
Published: March 2003

Background: The objective was to establish an ELISA to detect horse allergen in ambient air and settled dust.

Methods: Monoclonal antibodies (mAbs) were produced against extracts of horse antigen. Two mAbs were selected and used in a sandwich ELISA. By the aid of portable pumps, air samples were collected in one stable and in the ambient air surrounding this stable. Furthermore, settled dust was collected by wiping spots with pieces of fabric, at sites within 500 m of the stable.

Results: Extracts of horsehair could be extensively diluted and still be positive. Extracts of cat and dog allergen failed to be detected. Furthermore, the mAbs were shown to detect an IgE‐binding component. This was demonstrated by an ELISA using mAbs as capture antibody and sera from horse‐allergic subjects as secondary antibody with readout depending on anti‐IgE antibody. The sera with the highest RAST class to horse were positive in this ELISA. Airborne levels of horse allergen were over 500‐fold higher in the stable than just outside the stable and over 3000‐fold higher than at a residential building located only 12 m from the stable. Similarly, an inverse correlation was found between the distance to the stable and levels of “outdoor settled” horse allergen (r=−0.9, P<0.001).

Conclusions: We have developed a sensitive, horse‐allergen‐specific, mAb assay allowing detection of low levels of horse allergens. Raised levels of horse allergen were found outdoors only in the close vicinity of the stable.
Natural history of hay fever and pollen sensitization, and doctors' diagnosis of hay fever and pollen asthma in German schoolchildren
Authors: Riedinger F. , Kuehr J. , Strauch E. , Schulz H. , Ihorst G. , Forster J ,   and the Ozone Working Group
Published: March 2003

Background: In order to prevent pollen asthma by immunotherapy it is mandatory to know the best time to initiate it. Children with hay fever complaints are at considerable risk of developing pollen asthma. Population‐based data on their natural history is urgently needed.

Methods: A longitudinal cohort study was conducted over four years in six rural towns in Baden‐Wu¨rttemberg, Germany. A questionnaire with questions taken from the International Study of Asthma and Allergies in childhood (ISAAC) was filled in every spring and autumn. Hay fever complaints, asthma defining symptoms and new doctors' diagnosis of hay fever and asthma were recorded. Additionally a skin prick test with pollen allergens was performed every autumn.

Results: In 1996, 19.7% of 1101 elementary school children (age: 8.1–9.9 years (5–95%)) were found to be sensitized to pollen and 8.7% had already been diagnosed as having hay fever. In a pooled analysis of 2478 children‐summers, children with positive pollen sensitization had a significantly higher risk of developing hay fever symptoms (2.63; 2.17–3.10 odds ratio (OR); 95% confidence interval (CI)) and of being diagnosed as suffering from hay fever (7.88; 4.70–13.20). Furthermore, although their OR for the development of asthma symptoms during the pollen season was 3.88 (2.48–6.07 CI), it was only 0.69 (0.24–2.01 CI) for doctors' diagnosis of pollen asthma.

Conclusion: >Children of elementary school age with pollen sensitization and a history of hay fever are at considerable risk of getting pollen asthma, but they are not quickly diagnosed as such. Specific immunotherapy might be a means of preventing asthma completely in such a situation. Our data helps to estimate the sample size for intervention studies of this kind.
Sensitivity to methacholine and capsaicin in patients with unclear respiratory symptoms
Authors: Ternesten‐Hasséus E. , Farbrot A. , Löwhagen O. , Millqvist EVA
Published: March 2003

Background: Capsaicin, the pungent ingredient in red pepper, is known to stimulate coughing via the sensory nervous system. Earlier studies showed that patients with airway symptoms induced by chemicals and strong scents cough more after inhalation of capsaicin than healthy control subjects and this has been interpreted as a hyperreactivity of airway sensory nerves. Our aim was to study airway sensitivity to inhaled capsaicin and the occurrence of airway symptoms induced by strong scents in patients who underwent a bronchial methacholine test, primarily because of suspected asthma.

Methods: Fifty‐two consecutive patients referred for testing with methacholine were also provoked with inhaled capsaicin in increasing concentrations. Cough sensitivity to capsaicin was compared with that in 40 healthy control subjects.

Results: The patients coughed significantly more compared with the healthy control subjects with each dose of capsaicin (P < 0.0001). Twelve patients (23%) had a positive methacholine test, and of these, nine were diagnosed with asthma. There was no difference in capsaicin sensitivity between patients sensitive or insensitive to methacholine.

Conclusions: The majority of the patients had no increased sensitivity to methacholine but did demonstrate sensory hyperreactivity (SHR). SHR appears to be a common diagnosis in investigations of patients with obscure airway symptoms.
Localization of Der f 2 in the gut and fecal pellets of Dermatophagoides farinae
Authors: Jeong K. Y. , Lee I.‐Y. , Ree H.‐I. , Hong C.‐S. , Yong T.‐S.
Published: March 2003

Background:  House dust mite derived materials are known to be the most potent agent inducing allergic diseases. Localization of Der f 2 was attempted to specify the sites and concentrations of Der f 2 within the mite, which may indicate the importance of secreted materials and nonexcreted body components as allergen sources.

Methods:  Serial cryostat sections of embedded live mites and the fecal pellets, collected by brush, were immunoprobed using monoclonal antibody (mAb) 2F38 raised against recombinant (r) Der f 2.

Results:  Highest concentrations were found in the anterior midgut, implying that this is the site of Der f 2 synthesis and secretion. Digestive material and defecated fecal pellets were also labeled with mAb.

Conclusions: 
Our results show that the major allergen, Der f 2, found in the house dust mite
D. farinae is derived from the digestive tract, and is concentrated in the feces.
IgE‐mediated allergy to phytase – a new animal feed additive
Authors: Baur X. , Melching‐Kollmuss S. , Koops F. , Straßburger K. , Zober A.
Published: March 2003

Background: Although fungal phytase is frequently used as an additive to animal feed few investigations of its allergenic property have been conducted.

Methods: Fifty‐three subjects occupationally exposed to powdered phytase from Aspergillus niger were studied. Exposure data and symptoms were registered by the company physician.

Results: Thirty‐eight subjects complained of work‐related respiratory symptoms and 14 of them showed phytase‐specific IgE antibodies; only one asymptomatic subject revealed such antibodies. IgE antibodies were significantly more frequently found in the high‐exposure group (technical centre) when compared with the low‐exposure group (laboratories, experimental animal husbandry). Phytase‐specific IgG antibodies were present in 19 symptomatic (50%) and five (33%) asymptomatic subjects.

Conclusions: Our results demonstrate that powdered fungal phytase is a highly sensitizing substance whose inhalation exposure should be avoided. Hypersensitivity symptoms could be prevented by means of extensive hygienic measures and ongoing medical surveillance.
Immunological cross‐reactivity between lipid transfer proteins from botanically unrelated plant‐derived foods: a clinical study
Authors: Asero R. , Mistrello G. , Roncarolo D. , Amato S. , Caldironi G. , Barocci F. , Van Ree R.
Published: March 2003

Background: Lipid transfer proteins (LTP) are highly conserved and widely distributed throughout the plant kingdom. Recent studies demonstrated immunological cross‐reactivity between LTP from many botanically unrelated fruits and vegetables and concluded that LTP are pan‐allergens. This study aimed to evaluate the clinical relevance of such cross‐reactivity in a group of subjects monosensitized to LTP.

Methods: Twenty LTP‐hypersensitive patients were selected from a population of about 600 subjects with history of Rosaceae allergy by means of: 1) negative skin prick test (SPT) with a commercial birch pollen extract; 2) positive SPT with a commercial plum extract, rich in LTP but virtually lacking both Bet v 1‐like proteins and profilin; 3) in‐vitro IgE reactivity to the 9–10 kDa fraction of peach peel or immunoblot with peach peel showing a single band at 10 kDa; and 4) total inhibition of reactivity to whole peach extract (containing Bet v 1‐related allergen, profilin, and LTP) by purified peach LTP on enzyme‐linked immunoassay (ELISA). Allergy to foods other than Rosaceae was ascertained by careful interview and analysis of medical recordings. SPT with a large series of plant‐derived foods were carried out as well. The cross reactivity between LTPs from botanically unrelated plant‐derived foods was assessed by ELISA inhibition tests using walnut and peanut extracts as substrate, and peach LTP as inhibitor.

Results: All patients reported allergic reactions after the ingestion of at least one from a large number of vegetable foods other than Rosaceae, and in several cases clinical reactions were very severe (anaphylaxis, asthma, urticaria/angioedema). Nuts and peanuts were the most frequently reported causes of allergic reactions (80% and 40% of patients, respectively). All patients showed positive SPT to several non‐Rosaceae food extracts. SPT with nuts, peanut, legumes, celery, rice, and corn were positive in the majority of patients. In ELISA inhibition studies, absorption of sera with peach LTP caused complete inhibition of IgE reactivity to walnut and peanut in all cases.

Conclusion: LTP is a clinically relevant pan‐allergen. Most Rosaceae‐allergic, LTP‐hypersensitive patients experience adverse reactions after ingestion of botanically unrelated plant‐derived foods as well. In view of the high prevalence and severity of the allergic reactions induced, hazelnut, walnut, and peanut should be regarded as potentially hazardous for these patients.
The effect of storage on allergen and microbial agent levels in frozen house dust
Authors: Fahlbusch B. , Koch A. , Douwes J. , Bischof W. , Gehring U. , Richter K. , Wichmann H.‐E. , Heinrich J.
Published: March 2003

Background: House dust samples collected for exposure studies are often stored for variable time periods until analysis. However, there is currently no information on the effects of dust storage on the content of biocontaminants. Therefore, associations were analysed between the levels of mite allergens (Der p 1, Der f 1), cat allergen (Fel d 1) and microbial components (endotoxin, β(1→3)‐glucan) on the one hand and the storage duration of dust samples at −20°C on the other hand.

Methods: Within the framework of a study on the influences of INdoor factors and Genetics on Asthma (INGA), dust samples were collected from living room floors between June 1995 and August 1998 and extracted according to a standardized protocol. The concentrations of Der p 1, Der f 1, Fel d 1 and β(1→3)‐glucan were determined with specific enzyme immunoassays. Endotoxin content was quantified using a chromogenic kinetic Limulus amoebocyte lysate (LAL) test. All concentrations were expressed per gram of dust

Results: Dust samples (n = 1236) were obtained from 655 homes in Hamburg, Hettstedt, Zerbst and Bitterfeld. Storage duration (range 8–298 days) was grouped into four categories (≤ 60 d; 61–90 d; 91–120 d; > 120 d). After adjustment for city of residence and season of dust sampling, means ratios comparing categories 2–4 to the first category were not statistically significant for Der p 1, Der f 1, endotoxin and β(1→3 glucan). However, Fel d 1 concentrations significantly declined with increased storage times of dust samples.

Conclusions: Storage of house dust at −20°C for up to 10 months has no effect on mite allergen, endotoxin and β(1→3)‐glucan levels. A potential loss of Fel d 1 during storage of frozen dust samples needs further investigations by repeated measurements of allergen in identical dust samples.
A comparison of different allergometric tests, skin prick test, Pharmacia UniCAP® and ADVIA Centaur®, for diagnosis of allergic diseases in children
Authors: Ricci G. , Capelli M. , Miniero R. , Menna G. , Zannarini L. , Dillon P. , Masi M.
Published: March 2003

Background:  The diagnosis of allergic disease is performed by skin prick tests (SPT) or through the demonstration of specific IgE in a blood sample via an in vitro test. The measurement of IgE concentration against allergens provides critical information in clinical allergy. Standardized and reproducible methods contribute to the quality of diagnosis and treatment of allergic disease.

Methods:  In this study we evaluated the performance of a new specific IgE method, developed by ALK‐Abellò for Bayer Diagnostics to run on their ADVIA Centaur immunoassay system. One hundred and fifty‐one children with allergic diseases (both food and inhalant allergies) were tested for specific IgE (sIgE) via SPT and in vitro tests (UniCAP system, Pharmacia, and ADVIA Centaur immunoassay system, Bayer Diagnostics) and the test results were correlated with the clinical data.

Results:  Statistical analysis revealed no significant difference between the two in vitro tests compared with clinical history. The sensitivities and specificities are similar, but the UniCAP system method has higher sensitivity. In the children with cow's milk allergy, the UniCAP system has sensitivity of 91% and specificity of 70%; the ADVIA Centaur immunoassay has sensitivity of 82% and specificity of 74%. In hen's egg allergy, UniCAP system has 94% sensitivity and 64% specificity, and the ADVIA Centaur system has 88% sensitivity and 52% specificity. In inhalant allergies, the two methods show statistically similar performances for both grass pollen allergies (UniCAP sensitivity 100%, specificity 73%; ADVIA Centaur sensitivity 95%, specificity 79%) and in the dust mites allergies (UniCAP sensitivity 91%, specificity 62%; ADVIA Centaur sensitivity 86%, specificity 64%). In cat allergies, the systems showed equivalent results (UniCAP sensitivity 100%, specificity 71%; ADVIA Centaur sensitivity 100%, specificity 70%). Using the UniCAP system, the geometric mean of sIgE values in children with clinical allergy is significantly higher than in sensitized ones. The ADVIA Centaur system shows a similar trend with the exclusion of cow's milk and Dermatophagoides farinae allergens. With this last method the mean value of sIgE is higher in sensitized than in symptomatic children.

Conclusion:  The new ADVIA Centaur method compares favorably with the results obtained on the UniCAP system. If other studies continue to confirm this data, then the advantages are numerous: the use of only a small quantity of serum (25 µl per allergen), rapid turnaround time, minimal hands‐on time, and no interference from IgG.
An unusual fragile X sibship: female compound heterozygote and male with a partially methylated full mutation
Authors: Russo S. , Briscioli V. , Cogliati F. , Macchi M. , Lalatta F. , Larizza L.
Published: March 2003

We describe here a fragile X sibship of borderline retarded sister and brother born to carrier parents. The sister is a compound heterozygote (with a full mutation on one X chromosome and a pre‐mutation on the other X chromosome). The brother has a partially methylated full mutation. The activation ratio (AR) for the sister's pre‐mutation was 0.69 and the percent lack of methylation for the brother's full mutation was 73%. Intellectual and neuropsychological Wechsler Adult Intelligence Scale (W.A.I.S.) achievement tests reported full scale IQ scores of 74 in the sister and 77 in the brother. A significant discrepancy between verbal and performance IQ was found in the sister, indicating that her main impairment was in the cognitive area. The parents of this unusual sibship came from a small village, as did one of the two previously described cases of compound heterozygous females. These rare females raise special issues for genetic counselling in fragile X carrier couples, the frequency of which remains to be defined in different populations.
Effect of vitamin E on chromosomal aberrations in lymphocytes from patients with Down’s syndrome
Authors: Pincheira J , Navarrete MH , De La Torre C , Tapia G , Santos MJ
Published: March 2003

A possible protective effect of vitamin E ( dl‐α‐tocoferol) on chromosomal damage was evaluated in lymphocytes from patients with Down’s syndrome (DS) and from controls. This included the analysis of the basal and G2 chromosomal aberration frequencies in lymphocytes cultured with and without 100 μM vitamin E. The chromosomal damage in G2 was determined by scoring the number of chromosomal aberrations in lymphocyte cultures treated with 5 mM caffeine, 2 h before harvesting.Vitamin E treatment decreased the basal and G2 chromosomal aberrations both in control and DS lymphocytes. In DS cells, this protective effect, expressed as a decrease in the chromosomal damage, was greater (50%) than in controls (30%). These results suggest that the increment in basal and G2 aberrations yield in DS lymphocytes may be related to the increase in oxidative damage reported in these patients.
Molecular and clinical characterization of a patient with duplication of 1p36.3 and metopic synostosis
Authors: Heilstedt HA , Shapira SK , Gregg AR , Shaffer LG
Published: March 2003

Chromosome 1p duplications are rare. There have been only 11 reported cases of isolated 1p duplication, all of which were proximal, interstitial duplications. We present a patient with a terminal duplication of 1p (1p36.3). To our knowledge, this is the first such reported case. Our patient presented with metopic synostosis, rectal stenosis, atrial septal defect, and mildly delayed gross motor development. Molecular characterization using microsatellite marker analysis and fluorescence in situ hybridization (FISH) revealed an area of duplication between p58 and D1S2893, approximately 13 cM in size. We compare our patient's clinical findings with the clinical phenotype found in patients with the corresponding deletion of 1p36.3 and discuss the role of gene dosage in other deletion/duplication syndromes.
Internet resources for the clinical geneticist
Authors: Ouellette Francis
Published: March 2003

The Internet offers a number of resources to clinical geneticists. This review outlines some of these with special emphasis on sites present at the National Center for Biotechnology Information (NCBI) at the National Library of Medicine at the National Institutes of Health. Special attention is presented on how these various resources make use of PubMed, the premiere source of MEDLINE® information on the Internet. Three NCBI resources are presented here. 1) ‘Genes and diseases’: a general curated series of web pages outlining various references to known genetic diseases with links to relevant on‐line resources. 2) The Online Mendelian Inheritance in Man (OMIM) from Victor A. McKusick at Johns Hopkins University presents our current knowledge of all known human genetic diseases. 3) Human genome resources describe our current knowledge on the human genome project (HGP). A list of relevant uniform resource locators (URLs) is also included.
FISH analysis of terminal deletions in patients diagnosed with cri‐du‐chat syndrome
Authors: Catrinel Marinescu R , Johnson Elizabeth I , Grady Deborah , Chen Xiao‐Ning , Overhauser Joan
Published: March 2003

Most patients with cri‐du‐chat syndrome have a de novo deletion of the short arm of chromosome 5 (5p). In order to perform extensive phenotype–genotype correlation studies, a relatively easy method for the precise determination of the extent of a patient's deletion is essential. Towards this purpose, a set of minimally overlapping YAC clones that span 5p was identified. A BAC that maps at or near the 5p telomere was also used. A total of 110 patients with previously determined de novo terminal deletions by standard cytogenetic approaches were reanalyzed using the YAC clones and fluorescent in situ hybridization (FISH). Of the 110 samples, 4 patients were determined to have interstitial deletions, 1 patient had an unbalanced translocation, and no deletion could be detected in 2 patients. The FISH results in the 7 patients affect the clinical prognosis for some of these patients. These results demonstrate the need for supplementing standard cytogenetics with FISH analysis when an abnormal karyotype is detected.
An unaffected individual from a breast/ovarian cancer family with germline mutations in both BRCA1 and BRCA2
Authors: Moslehi Roxana , Russo Donna , Phelan Catherine , Jack Elaine , Antman Karen , Narod Steven
Published: March 2003

Currently many centers offer testing for three specific mutations, 185delAG, 5382insC, and 6174delT, in the BRCA1 and BRCA2 genes to Ashkenazi Jewish individuals at high risk for breast and ovarian cancer. We recently tested members of a family with multiple cases of breast and ovarian cancer (Family R014). The proband in this family tested positive for the 185delAG mutation. The unaffected sister of the proband tested positive for both the 185delAG and the 6174delT mutations. Further testing and review of the family history suggest that both mutations may have come from a maternal grandfather and passed down for two generations. Counseling of the unaffected double heterozygote individual in this family is complicated by lack of information on the risk of breast, ovarian, and other cancers in such individuals. A better understanding of these risks will depend on the identification and study of more individuals carrying mutations in both the BRCA1 and BRCA2 genes. Our study emphasizes the importance of testing Ashkenazi Jewish individuals from high‐risk breast and ovarian cancer families for all three common BRCA1 and BRCA2 mutations identified in this ethnic group.
Correlations between individual clinical manifestations and CTG repeat amplification in myotonic dystrophy
Authors: Marchini Corrado , Lonigro Renata , Verriello Lorenzo , Pellizzari Lucia , Bergonzi Paolo , Damante Giuseppe
Published: March 2003

Myotonic dystrophy (DM) is a multisystemic disease caused by the expansion of a CTG repeat, located in the 3′‐untranslated region of the DMPK gene. The number of CTG repeats broadly correlates with the overall severity of the disease. However, correlations between CTG repeat number and presence/absence or severity of individual clinical manifestations in the same patients are yet scarce. In this study the number of CTG repeats detected in blood cells of 24 DM subjects was correlated with the severity of single clinical manifestations. The presence/absence of muscular atrophy, respiratory insufficiency, cardiac abnormalities, diabetes, cataract, sleep disorders, sterility or hypogonadism is not related to the number of CTG repeats. Muscular atrophy and respiratory insufficiency are present with the highest frequency, occurring in 96 and 92% of the cases, respectively. A significant correlation was found with age of onset (r=−0.57, p<0.01), muscular disability (r=0.46, p<0.05), intellective quotient (r=−0.58, p<0.01) and short‐term memory (r=−0.59, p<0.01). Therefore, the CTG repeat number has a predictive value only in the case of some clinical manifestations, this suggesting that pathogenetic mechanisms of DM may differ depending on the tissue.
Localization of an acromesomelic dysplasia on chromosome 9 by homozygosity mapping
Authors: Ianakiev P , Kilpatrick Mw , Daly Mj , Zolindaki A , Bagley D , Beighton G , Beighton P , Tsipouras P
Published: March 2003

The acromesomelic dysplasias (AMDs) are a group of genetic disorders that primarily affect the middle and distal segments of the extremities. A form of AMD is present on the isolated island of St Helena in the South Atlantic, which has a population of approximately 5500 derived from a number of founder individuals. DNA from four affected individuals and 11 first‐degree relatives in four related nuclear families segregating an AMD was collected for gene mapping studies. Six consecutive markers on chromosome 9, spanning an approximately 5 cM region, showed identical homozygosity in all affected individuals, thus identifying a region of homozygosity by descent. Multipoint analysis generated a maximum lod score of Z=2.85. These data localize the gene for this dysplasia to the pericentromeric region of chromosome 9 where the gene for the Maroteaux form of AMD is situated. The identification of the gene responsible for this disorder may shed further light on the complex processes involved in limb morphogenesis.
Mutation and transcription analysis of transthyretin gene in Italian families with hereditary amyloidosis: a putative novel ‘hot spot’ in codon 47
Authors: Ferlini A , Obici L , Manzati E , Biadi O , Tarantino E , Conigli P , Merlini G , D'alessandro M , Mazzaferro V , Tassinari Ca , Salvi F
Published: March 2003

Transthyretin gene mutations are associated with autosomal dominant familial amyloidosis. The commonest phenotype in the patients is peripheral neuropathy, but restrictive cardiomyopathy is also a frequent sign. More than 70 different mutations in the gene have been described. Although these mutations are randomly distributed, some hot spots have also been reported notably at position 6, 30, 33, 58, 109, 119 and 122. A few of these codons contain a CpG dinucleotide. We describe an additional ‘hot spot’ occurring at codon 47, in which we report one novel and two previously described mutations. This codon, however, does not contain a CpG dinucleotide, suggesting that other mechanisms might be responsible for the allelic heterogeneity. All the reported mutations in codon 47 are located in the exon 2 consensus sequence and are potentially involved in splicing. We performed transcription analysis on two livers obtained from transplanted patients carrying the Ala47 mutation. These livers showed a normally spliced message, indicating that this mutation does not affect splicing.
Apolipoprotein B‐100 gene Xba I polymorphism and cholesterol gallstone disease
Authors: Han Tianquan , Jiang Zhaoyan , Suo Guangjun , Zhang Shengdao
Published: March 2003

The apolipoprotein (apo) B gene Xba I polymorphism is associated with alterations in serum lipids. Disturbances in serum lipids may be a risk factor for cholesterol gallstone disease. However, the relation between the Xba I polymorphism and cholesterol gallstones is unknown. This study was aimed at characterizing the polymorphism of the apo B gene Xba I in patients with gallbladder stones and the association of Xba I polymorphism with serum lipids. Xba I genotypes were measured by PCR‐RFLP, and serum lipids assayed in 190 patients with gallbladder stones and 441 control subjects. The frequency of the X+/− genotype (20.63 vs. 7.94%) and X+ allele (10.79 vs. 3.97%) was significantly higher in the patient group than in the control group. Patients with the X+/− genotype had a significantly higher concentration of total cholesterol, low‐density lipoprotein (LDL)‐cholesterol, and apo B in serum than patients with the X−/− genotype. The X+ allele of the apo B gene is characterized by a higher cholesterol concentration and a higher LDL‐cholesterol concentration in serum, and it may be a marker for increased risk of cholesterol gallstone disease.
Mutations ofGJB2in three geographic isolates from northern Tunisia: evidence for genetic heterogeneity within isolates
Authors: Ben Arab Saïda , Hmani Mounira , Denoyelle Françoise , Boulila‐Elgaied Amel , Chardenoux Sebastien , Hachicha Slah , Petit Christine , Ayadi Hammadi
Published: March 2003

Geographically isolated populations have been successfully used to localize genes for recessive inherited diseases, including non‐syndromic sensorineural recessive deafness (NSRD). To date, 25 loci for NSRD have been localized on human chromosomes (DFNB loci), and six of the corresponding genes have been identified.  Here, we report on the contribution of the DFNB1 locus (GJB2gene) to NRSD in seven affected families living in three northern Tunisian geographic isolates, and we provide evidence for genetic heterogeneity within isolates. This finding challenges the classical view of a single ‘founder’ mutation segregating in such isolates.