bluuebunny/crossref_metadata_2025 huggingface dataset:
Allergens of Epicoccum nigrum grown in different media for quality source material
Authors: Bisht V. , Singh B. P. , Arora N. , Sridhara S. , Gaur S. N.
Published: March 2003

Background: The Epicoccum nigrum (EN) extract used in allergy disorders exhibits batch‐to‐batch variations in protein composition and allergenic potency. In this study, the allergens of EN grown in different media were investigated.

Methods: EN was grown in five different nutrient media as stationary cultures at 25°C for 5–23 days. The growth pattern was characterized by measuring dry weight, and protein and carbohydrate content. The antigenic and allergenic content of EN extract was evaluated with EN‐positive patients' sera and antibodies raised in rabbit.

Results: The growth of EN in Czapeck Dox medium yielded insufficient material, while Sabouraud's broth with yeast extract (SBY) gave maximum spore‐mycelial mass and protein content. Potato dextrose broth (PDB) and potato dextrose agar (PDA) showed higher dry weight and protein in 7–9‐day cultures. SDS–PAGE resolved 26, 22, and 21 protein bands in EN extracts from cultures of day‐13 SBY, day‐7 PDB, and day‐9 PDA, respectively. IgE/IgG immunoblots showed more allergenic (
25)/antigenic (
25) bands in EN cultured in SBY than in the others. Specific IgE ELISA and intradermal tests showed EN extract from day‐13 culture in SBY to be the most potent.

Conclusions: The day‐13 culture of EN in SBY was the most potent and may be selected for preparing EN extracts for diagnosis of allergy and future studies.
Involvement of inferior turbinate mucosa in chronic sinusitis – localization of T‐cell subset
Authors: Grevers G. , Klemens A. , Sturm C. , Menauer F.
Published: March 2003

Background: In chronic sinusitis (CS), different subsets of leukocytes are involved in development of persistent inflammation of the nasal mucosa. The localization and differentiation of these infiltrating lymphocytes may help us to understand the inflammatory interactions in the epithelium, lamina propria, and seromucous glands of the nasal mucosa in CS.

Methods: We examined frozen sections of inferior turbinates from 14 patients with nonallergic CS and 10 normal nonallergic controls. We used the avidin‐biotin‐peroxidase (ABC) technique with monoclonal antibodies against CD3 (total T cells), CD4 (T‐helper/inducer cells), CD8 (T‐suppressor/cytotoxic cells), CD22 (B cells), CD56 (natural killer cells), elastase (neutrophil granulocytes), eosinophil cationic protein (eosinophil granulocytes), and CD68 (macrophages).

Results: We found significant increases (P<0.05) of CD3, CD4, and CD8 T cells and B cells in the nasal mucosa of patients with CS. The number of CD68 cells and eosinophils showed no significant rise.

Conclusions: The different types of leukocytes play a key role in the defense of the respiratory tract. The analysis of the distribution of cells in the epithelium, mucosa, and glands of the inferior turbinate confirmed that nonallergic CS is, in fact, chronic, bacterial rhinosinusitis involving the inferior turbinates, and that the pathomechanism is therefore different from that of nasal polyposis.
Aluminium‐induced granulomas after inaccurate intradermal hyposensitization injections of aluminium‐adsorbed depot preparations
Authors: Vogelbruch M. , Nuss B. , Körner M. , Kapp A. , Kiehl P. , Bohm W.
Published: March 2003

Background: The development of persistent subcutaneous nodules at the injection sites of aluminium‐adsorbed hyposensitization solutions is rare. These nodules have been interpreted as a delayed, granulomatous hypersensitivity reaction to aluminium. We report for the first time a case of persistent intradermal granulomas that developed at the sites of inaccurate intradermal, instead of subcutaneous, hyposensitization injections.

Methods: An intradermal nodule was excised and processed for histopathology, scanning electron microscopy, and X‐ray microanalysis. Intradermal and patch tests with aluminium hydroxide were performed.

Results: Histologically, the nodule presented a pattern of granulomatous inflammatory reaction surrounding foci of necrotic tissue. Scanning electron microscopy and X‐ray microanalysis revealed deposits of aluminium within the granulomas. Patch tests with aluminium hydroxide were negative, and intradermal tests caused persistent intradermal granulomas. Subsequent hyposensitization therapy in our department with the usual subcutaneous injections of aluminium‐adsorbed allergen extracts was well tolerated by the patient.

Conclusions: Local toxic effects of aluminium may be crucial in the development of persistent intradermal injection‐site granulomas. Such intradermal nodules may develop even if the subcutaneous route is well tolerated. We conclude that inaccurate intradermal injections of aluminium‐containing solutions have to be strictly avoided.
The prevalence of skin‐test‐positive allergic rhinitis in Danish adults: two cross‐sectional surveys 8 years apart.The Copenhagen Allergy Study
Authors: Linneberg A. , Jørgensen T. , Nielsen N. Henrik , Madsen F. , Frølund L. , Dirksen A.
Published: March 2003

Background: It is disputed whether increases in self‐reported respiratory allergy represent a true increase or merely increased recognition. We aimed to investigate whether the prevalence of skin‐prick‐test (SPT)‐positive allergic rhinitis had increased in an adult general population in Copenhagen, Denmark.

Methods: Two cross‐sectional surveys were carried out in 1990 and 1998. A screening questionnaire on respiratory symptoms in random samples of 15–41‐year‐olds preceded both surveys. Among the responders, random samples were invited to a health examination including SPT. Totals of 312 (participation rate 74.6%) and 482 (participation rate 53.4%) subjects were examined in 1990 and 1998, respectively. Diagnoses of SPT‐positive allergic rhinitis were based on a history of nasal symptoms on exposure to allergens and SPT positivity to allergens.

Results: The prevalence of a diagnosis of SPT‐positive allergic rhinitis increased from 12.9% to 22.5% (adjusted odds ratio 1.94, 95% CI 1.30–2.90), whereas the prevalence of a positive SPT (allergen histamine wheal ratio ≥0.5) to one or more of 10 allergens increased from 27.7% to 33.9% (adjusted odds ratio 1.47, 95% CI 1.05–2.05).

Conclusions: The prevalence of SPT‐positive allergic rhinitis has increased significantly. Our findings indicate that a true increase in respiratory allergy has occurred.
The effect of Chinese herbal medicine, xiao‐qing‐long tang (XQLT), on allergen‐induced bronchial inflammation in mite‐sensitized mice
Authors: Kao S. T. , Wang S. T. , Yu C. K. , Lei H. Y. , Wang J. Y.
Published: March 2003

Background: There are detailed descriptions of the clinical experiences and prescriptions of asthma in traditional Chinese medicine. Xiao‐qing‐long tang (XQLT), or sho‐seiryo‐to by its Japanese name, is one of the Chinese herbal medicines used to treat bronchial asthma and allergic rhinitis for centuries. However, the therapeutic mechanisms of this medication are still far from clear. In this study, a house‐dust‐mite (Dermatophagoides pteronyssinus [Der p])‐sensitized murine model of asthma was used to evaluate the immunomodulatory effect of XQLT on the allergen‐induced airway inflammation in asthma.

Methods: Three different protocols were designed to evaluate the treatment and/or long‐term prophylactic effect of XQLT in Der p‐sensitized mice. XQLT extracts (1 gm/kg) were administered to sensitized mice 1 h before allergen challenge (AC) (group A), 24 h after AC (group B), and every other day six times before AC (group C), respectively. Cellular infiltration and T‐cell subsets in the bronchoalveolar lavage fluid (BALF) of allergen‐challenged mice were analyzed. Intrapulmonary lymphocytes were also isolated to evaluate their response to allergen stimulation.

Results: When XQLT was administered to the sensitized mice before AC (groups A and C), it suppressed airway inflammation by decreasing the number of total cells and eosinophil infiltration in the BALF, and downregulated the allergen‐ or mitogen‐induced intrapulmonary lymphocyte response of sensitized mice as compared to those of controls. This immunomodulatory effect of XQLT may be exerted through the regulation of T‐cell subsets by elevation or activation of the CD8+ and double‐negative T‐cell population in the lung. However, the administration of XQLT to sensitized mice 24 h after AC (group B) did not have the same inhibitory effect on the airway inflammation as XQLT given before AC.

Conclusions: The administration of XQLT before AC has the immunomodulatory effect of reducing bronchial inflammation in the allergen‐sensitized mice.
Reduction of exercise‐induced asthma oxidative stress by lycopene, a natural antioxidant
Authors: Neuman I. , Nahum H. , Ben‐Amotz A.
Published: March 2003

Background: Lycopene has previously been shown to have high antioxidative activity. In view of the controversy regarding the beneficial effect of antioxidants on asthma, the acute effects of lycopene (LYC‐O‐MATOTM) on airway hyperreactivity were assessed in patients with exercise‐induced asthma (EIA).

Methods: Twenty patients with EIA participated in our study to verify the antioxidative effects. The test was based on the following sequence: measurement of baseline pulmonary function, 7‐min exercise session on a motorized treadmill, 8‐min rest and again measurement of pulmonary function, 1‐week, oral, randomly administered, double‐blind supplementation of placebo or 30 mg/day of lycopene (LYC‐O‐MATO), measurement of pulmonary function at rest, 7‐min exercise session, and 8‐min rest and again measurement of pulmonary function. A 4‐week washout interval was allowed between each protocol.

Results: All patients given placebo showed significant postexercise reduction of more than 15% in their forced expiratory volume in 1 s (FEV1). After receiving a daily dose of 30 mg of lycopene for 1 week, 11 (55%) patients were significantly protected against EIA. Serum analyses of the patients by high‐pressure liquid chromatography detected in the lycopene‐supplemented patients an elevated level of lycopene compared to the placebo group, with no change in retinol, tocopherols, or in the other carotenoids.

Conclusions: Our results indicate that a daily dose of lycopene exerts a protective effect against EIA in some patients, most probably through an in vivo antioxidative effect.
Sensitization to the fungus Hemileia vastatrix (coffee leaf rust)
Authors: Croce Portocarrero M. A. , Da Costa Manso E. Rosa , Gambale W. , Takayama L. , Oliveira Andrade C. E. , Pereira Pinto J. H. , Morato Castro F. F. , Croce J.
Published: March 2003

Background: The aim of the present study was to determine the existence of sensitization to the fungus Hemileia vastatrix (coffee leaf rust) in a sample of the Brazilian population. This fungus attacks coffee plantations, and in some regions of Brazil the concentration of its spores in the air can be very high.

Methods: A total of 378 individuals underwent skin tests (prick and intradermal tests) with H. vastatrix extract. The subjects were divided into four groups according to the occurrence of atopy and the region where they lived (coffee‐growing or non‐coffee‐growing regions), and another group (V) consisted of 50 rural workers employed on coffee plantations. The presence of specific IgE against the fungus H. vastatrix in sensitized individuals was demonstrated in vitro by immunoblotting.

Results: There was no statistical difference in comparing the results with intradermal or prick tests. The incidence of positive tests was significantly higher among atopic individuals residing in coffee‐growing regions (14.7%). Among rural workers, 10% showed positive tests. Immunoblotting revealed specific IgE against 20 protein bands of H. vastatrix.

Conclusions: The fungus H. vastatrix may be an important allergen in coffee‐producing countries. The sensitization is more frequent among atopic individuals residing in coffee‐growing regions.
Desloratadine in the treatment of chronic idiopathic urticaria
Authors: Ring J.
Published: March 2003

Chronic idiopathic urticaria (CIU) is a common dermatologic disorder that may severely impair quality of life. Patients may suffer symptoms such as pruritus and disfigurement due to wheals for years or decades. Advances have been made in the last 10 years with the identification of an autoimmune pathogenesis in a significant proportion of patients. Despite this, treatment remains symptomatic, and antihistamines are the first choice of therapy once the diagnosis of CIU has been established. The goal of treatment is rapid, long‐lasting symptom relief, and currently available antihistamines fail to provide this in many cases. Desloratadine is a novel, potent H1‐receptor antagonist with additional inhibitory effects on inflammatory mediators such as cytokines and adhesion molecules. Newly published data on the efficacy and safety of desloratadine in CIU is highly encouraging, suggesting that the drug may improve symptom control above that currently available.
Molecular features determining lymphocyte reactivity in allergic contact dermatitis to chloramphenicol and azidamphenicol
Authors: Sachs B. , Erdmann S. , Al Masaoudi T. , Merk H. F.
Published: March 2003

Background: We report on two cases of allergic contact dermatitis to chloramphenicol and azidamphenicol respectively, with in vivo and in vitro lymphocyte reactivity to both compounds. The molecular features determining lymphocyte reactivity were explored because chloramphenicol, azidamphenicol, and thiamphenicol exhibit almost identical chemical structures.

Methods: With chloramphenicol, azidamphenicol, and the chemically related thiamphenicol, we performed patch tests and lymphocyte transformation tests with both patients. Furthermore, the interleukin‐5 and interferon‐γ concentrations in the cultures of peripheral blood mononuclear cells of one patient were determined.

Results: Patch tests showed delayed hypersensitivity reactions to chloramphenicol and azidamphenicol, but not to thiamphenicol. These results were confirmed by lymphocyte transformation tests with peripheral blood mononuclear cells of the patients, showing a proliferative T‐cell response to azidamphenicol and chloramphenicol. Moreover, lymphocytes from one patient secreted large amounts of interleukin‐5, but not of interferon‐γ upon coculture with azidamphenicol.

Conclusions: Since lymphocyte reactivity was observed to chloramphenicol and azidamphenicol, but not to thiamphenicol, the epitope(s) recognized by the allergen‐reactive T cells may be formed by the nitro‐group of the benzene ring shared by chloramphenicol and azidamphenicol.
Is obesity a risk factor for childhood asthma?
Authors: Von Kries R. , Hermann M. , Grunert V. P. , Von Mutius E.
Published: March 2003

Background: In adolescents and adults, an association between obesity and asthma was found in females. Does this sex‐specific association already exist in young children?

Methods: Questionnaire data on 9357 5‐ and 6‐year‐old German children were collected in 1997 in two rural regions in Bavaria. The diagnosis of asthma, hay fever, and eczema was ascertained with the ISAAC core and other validated questions. Overweight was defined by a BMI of >90th and ≤97th percentile and obesity by a BMI of >97th percentile.

Results: The lifetime prevalence of doctor's diagnosed asthma in girls was 3.5% (95% CI 2.9–4.1%) for normal weight, 5.8% (95% CI 3.2–8.4%) for overweight, and 10.3% (95% CI 5.3–15.2%) for obesity, whereas no relation to weight was found in boys. Hay fever and eczema were unrelated to weight in girls and boys. The adjusted odds ratio for asthma in girls was 2.12 (95% CI 1.22–3.68) for overweight and 2.33 (95% CI 1.13–4.82) for obesity.

Conclusions: A sex‐specific association with doctor's diagnosed asthma was also observed in girls at school entry. Since this association was confined to doctor's diagnosed asthma in the absence of other atopic conditions, and no association with other atopic manifestations was found, we hypothesize that this association is related to factors other than atopic sensitization.
Specific IgE and IgG to gelatin in children with systemic cutaneous reactions to Japanese encephalitis vaccines
Authors: Sakaguchi M. , Miyazawa H. , Inouye S.
Published: March 2003

Background: Systemic allergic reactions to Japanese encephalitis (JE) vaccine that include urticaria, angioedema, and rash have been reported. In Japan, children who suffered from allergic immediate‐type reactions to JE vaccine had antigelatin IgE in their sera. However, the immunologic mechanism of allergic nonimmediate‐type reactions that consist of cutaneous signs appearing several hours or more after JE vaccination has not been defined.

Methods: Serum samples were taken from 28 children who showed allergic nonimmediate‐type cutaneous reactions to JE vaccine. Furthermore, serum samples were taken from 10 children who showed allergic immediate‐type reactions with cutaneous signs and/or respiratory symptoms to JE vaccine. We have defined an immediate‐type reaction as one occurring within 1 h after vaccination.

Results: Of 10 children who showed immediate‐type reactions, all had antigelatin IgE and IgG. Of 28 children who showed systemic nonimmediate‐type reactions, one had antigelatin IgE and nine (32%) had antigelatin IgG. The child who had antigelatin IgE showed urticaria 2 h after JE vaccination.

Conclusions: These results suggest that some children who showed allergic nonimmediate‐type reactions to JE vaccine were sensitized to gelatin.
Comparison of ELISA for tissue transglutaminase autoantibodies with antiendomysium antibodies in pediatric and adult patients with celiac disease
Authors: Salmaso C. , Ocmant A. , Pesce G. , Altrinetti V. , Montagna P. , Descalzi D. , Martino S. , Bagnasco M. , Mascart F.
Published: March 2003

Background: Tissue transglutaminase (t‐TG) is the main autoantigen recognized by the endomysium antibodies (EMA) observed in patients with celiac disease (CD). The aim of the study was to assess an ELISA method for t‐TG antibodies (t‐TGA) with respect to EMA IF assay in pediatric and adult patients.

Methods: t‐TGA were analyzed by ELISA in 220 sera samples: 82 patients with biopsy‐proven untreated CD (23 adults and 59 children), 14 CD children on gluten‐free diet, 18 asymptomatic relatives of CD patients, and 106 age‐matched control patients with gluten‐unrelated gastrointestinal diseases (58 adults and 48 children). Serum IgA EMA were tested on umbilical cord sections in all patients.

Results: The great majority (92.7%) of untreated CD patients (both adults and children) were t‐TGA positive (values ranging from 20.1 to >300 AU). None of the child control patients and only two out of 58 (3.4%) of the adults with unrelated gastrointestinal diseases had serum t‐TGA positivity; two out of 18 first‐degree relatives with biopsy‐proved silent CD were t‐TGA (as well as EMA) positive. Finally, two out of 14 CD children, assuming a gluten‐free diet, had serum t‐TGA (as well as EMA). A highly significant correlation (P<0.001) was observed between t‐TGA concentrations and EMA. t‐TGA showed a sensitivity of 87% and 95%, a specificity of 97% and 100% for adults and children, respectively.

Conclusions: The method is highly sensitive and specific in the diagnosis of CD and is promising as a tool for routine diagnostic use and population screening, especially in children.
Occupational contact urticaria from diglycidyl ether of bisphenol A epoxy resin
Authors: Kanerva L. , Pelttari M. , Jolanki R. , Alanko K. , Estlander T. , Suhonen R.
Published: March 2003

Background: Epoxy resin (ER) is a common cause of occupational allergic contact dermatitis (ACD), but contact urticaria from ER is very rare.

Methods and Results: A plastic‐product worker first developed ACD from diglycidyl ether of bisphenol A (DGEBA) epoxy resin, and subsequent exposure resulted half a year later in contact urticaria: first with edema of the lips and eyelids, and later an urticarial reaction on the upper chest, with strong swelling of the eyelids and tightness of the throat. The diagnosis was based on a positive skin prick test to his “own” ER compound, a positive prick test reaction to DGEBA, and a positive skin provocation test with the ER compound and DGEBA. The contact urticaria test reaction was strongly aggravated when the allergen was wiped off with an alcohol solution, apparently because the solution enhanced the penetration of the allergen.

Conclusions: Our case is of interest, first, because contact urticaria from ER is very rare, and second, because this is the second report in which a strongly intensified contact urticaria reaction was provoked by an alcohol solution. We suggest that if the contact urticaria provocation test with low‐molecular‐weight chemicals is negative, a contact urticaria provocation test with alcohol (CUPTA) should be performed.
Influence of food processing on the allergenicity of celery: DBPCFC with celery spice and cooked celery in patients with celery allergy
Authors: Ballmer‐Weber B. K. , Hoffmann A. , Wüthrich B. , Lüttkopf D. , Pompei C. , Wangorsch A. , Kästner M. , Vieths S.
Published: March 2003

Background: Celery root is often consumed in a processed form as a cooked vegetable or as a spice. So far, however, there has been no information about the allergenicity of processed celery in celery‐allergic patients.

Methods: In 12 patients with a history of allergic reactions to raw or raw and cooked celery, double‐blind placebo‐controlled food challenges (DBPCFCs) with raw celery (n = 10), cooked celery (110°C/15 min; n = 11), and celery spice (n = 5) were performed. Nine patients underwent an open mucosal challenge with four samples of canned celery retorted at Co‐values (cooking effect) of 7.45–76.07 (corresponding to the time periods in minutes at a thermal influence of 100°C). IgE immunoblot analysis of celery extract was performed with sera of all challenged patients. The thermal stability of celery allergen was investigated by enzyme allergosorbent test (EAST) inhibition. Furthermore, intraperitoneal immunization of mice followed by a rat basophil leukemia (RBL) cell mediator release assay was used as a biological in vitro model to assess the allergenicity of processed celery.

Results: Six out of 11 patients showed a positive DBPCFC to cooked celery and five out of five patients to celery spice. Allergenicity of celery was preserved in four patients with a positive DBPCFC to cooked celery even if celery was treated at a Co‐value of 76.07. Patients with positive DBPCFC to cooked celery reacted to known celery allergens (Api g 1, Api g 4, cross‐reactive carbohydrate determinants CCD). EAST inhibition showed that heat resistance of celery allergens decreases in the following order: CCD > Api g 4 > Api g 1. Accordingly, five of six patients with a positive DBPCFC to cooked celery were sensitized to profilin and/or CCD. The murine model reflected the reactivity of patients sensitized to the major allergen Api g 1.

Conclusions: 1) In a subset of patients with a positive DBPCFC to cooked celery, celery remains allergenic even after extended thermal treatment (76.07 min/100°C). 2) Celery spice is allergenic for patients with an allergy to raw celery. 3) RBL cells sensitized with mouse IgE to raw celery may serve as a useful tool for screening the potential allergenicity of heat‐processed products containing celery.
Prick tests to aeroallergens: is it possible simply to wipe the device between tests?
Authors: Piette V. , Bourret E. , Bousquet J. , Demoly P.
Published: March 2003

Background: Improperly performed skin prick tests (SPT) can lead to wrong allergy diagnosis and incorrect treatment. To overcome false‐positive results it is recommended to change the puncture device between each test, although very few studies have examined the real drawbacks (false‐positives) and advantages (time and cost savings) of using only one device.

Methods: Two groups of 20 patients with rhinitis or asthma, sensitized to either house‐dust mites or grass pollens, had successive serial SPT to 9% codeine phosphate and the relevant allergen using the same needle or lancet, wiped between each test.

Results: With both the needle and the lancet, there were 12.5–67.5% false‐positive results using the house‐dust mite or grass pollen allergen extracts, respectively. There were no false‐positive results with the 9% codeine phosphate.

Conclusions: Our study shows that this technique is not reliable as it provoked an unacceptable number of false‐positive results.
Urinary leukotriene levels are increased during exacerbation of atopic eczema/dermatitis syndrome. Relation to clinical status
Authors: Adamek‐Guzik T. , Guzik T. J. , Czerniawska‐Mysik G. , Korpanty G. , Mastalerz L. , Radwan J. , Szczeklik A.
Published: March 2003

Background:  Leukotrienes are potent mediators of allergic inflammation and their role in the pathogenesis of allergic disorders, particularly asthma, is well established. Their importance in the pathogenesis of atopic eczema/dermatitis syndrome (AEDS) is still unclear. We aimed to compare urinary cysteinyl leukotriene (Cys‐LT) levels during exacerbation and remission of AEDS in relation to clinical status, IgE levels, and eosinophil counts.

Methods:  Urinary Cys‐LTs were measured by direct enzyme immunoassay in 17 adult patients with AEDS and in 17 healthy controls in whom atopy had been excluded. Cys‐LTs were compared during exacerbation and remission of AEDS in relation to the clinical status measured by SCORAD. Total IgE levels were measured by enzyme‐linked immunoassay (ELISA).

Results: 
Mean clinical score during the exacerbation was 64.3 ± 3.1 and during remission 22.4 ± 4 (
P
 < 0.01). Cys‐LTs levels were significantly higher during the exacerbation of AEDS than in the control group (230.9 ± 20.8 vs 123.2 ± 9.9 pg/mg creatinine;
P
 < 0.005). During the remission, the difference between AEDS patients and the control group was not significant (96.3 ± 8.7
vs
123.2 ± 9.9 pg/mg creatinine;
P
 = 0.8). During AEDS exacerbation Cys‐LTs levels were significantly correlated with the clinical status (
r
S
 = 0.73,
P
 < 0.01) and with eosinophil counts (
r
 = 0.86;
P  < 0.01) but not with the duration of the disease, age of patients, or IgE levels.

Conclusions:  Our results point to enhanced biosynthesis of Cys‐LTs during the AEDS exacerbations. Inflammatory cells, e.g. eosinophils are the most probable source of Cys‐LTs. A strong correlation between Cys‐LT levels and clinical status may in part explain preliminary clinical observations of efficacy of leukotriene antagonists in alleviating symptoms of AEDS.
The 3 mm skin prick test (SPT) threshold criterion is not reliable for Tyrophagus putrescentiae: the re‐evaluation of SPT criterion to dust mites
Authors: Kanceljak‐Macan B. , Macan J. , Plavec D. , Klepac T. , Milković‐Kraus S.
Published: March 2003

Background: The mean wheal diameter ≥ 3 mm is the usual criterion for positive skin prick test (SPT) reaction to dust mites. The study assessed the accuracy of this SPT criterion with respect to specific IgE values of above 0.35 kUA/l (+ sIgE).

Methods: Specific IgE (ImmunoCAP, Pharmacia AB Diagnostics, Uppsala, Sweden) and standard SPT to Dermatophagoides pteronyssinus (DP) and farinae (DF), Lepidoglyphus destructor (LD) and Tyrophagus putrescentiae (TP) (ALK, Hørsholm, Denmark) were performed in a random sample of 457 subjects, of whom 273 men (mean age 35.3 ± 11.0 years) and 184 women (mean age 37.9 ± 9.5 years). Statistical analysis was performed using the chi‐square test, regression analysis and discriminant analysis.

Results: When the mean wheal diameter of ≥ 3 mm was considered positive (+ SPT), the correlation between + SPT and + sIgE was 0.47 for DP (P < 0.001), 0.43 for DF (P = 0.004), 0.35 for LD (P = 0.03) and 0.37 for TP (P = 0.014). Regarding + sIgE, this SPT criterion has a specificity of 92.2% for DP, 82.3% for DF, 80.8% for LD and 70.1% for TP. When the value 4.5 mm was taken as the threshold for the positive SPT reaction to TP, specificity increased significantly from 70.1% to 86.4% (χ2 = 32.04, P < 0.001).

Conclusions: The 3 mm SPT threshold criterion is not reliable in evaluating sensitization to TP due to an insufficient specificity of the allergen extract to this mite. It is advisable either to re‐evaluate the TP allergen extract or change the threshold criterion for positive SPT reaction to TP.
The increased histamine release in ischaemic heart disease patients undergoing coronaroangiography is not mediated by specific IgE
Authors: Rodriguez R. M. , Guéant J.‐L. , Aimone‐Gastin I. , Gérard P. , Amoghly F. , Bellou A. , Jullière Y. , Faure G. , Danchin N. , Romano A.
Published: March 2003

Background:  The release of histamine by iodinated contrast media (ICM) is higher in coronary artery disease patients than in noncoronary patients during coronary angiogram.

Methods:  Eighty‐eight patients who underwent a coronary angiography were classified either as having coronary artery disease or as noncoronary patients. Histamine concentration was higher than the 6.8 nM upper limit in 7 cases (group 1), of whom six were coronary artery disease patients. We compared the IgE and complement fractions in plasma of these patients to two control groups with normal histamine blood level, one (group 2) with and the other (group 3) without coronary artery disease.

Results: 
No difference of total IgE and C
3c
and C
4 complement fractions was found among the three groups. Anti‐ioxaglate IgE‐RIA was positive in only one patient from group 1. The affinity of drug‐IgE binding in the serum of this patient was very low (Kd: 18.7 mM). The level of anti‐ICM IgE detected by ioxitalamate‐ and iomeprol‐Sepharose RIA was significantly higher in groups 2 and 3 than in group 1.

Conclusions:  The higher histamine release in ischaemic heart disease patients undergoing coronaroangiography is not mediated by IgE or complement activation. Further studies are needed to investigate the implication of histamine release factors.
Leukotriene receptor antagonists in the treatment of asthma: an update
Authors: Balzano G. , Fuschillo S. , Gaudiosi C.
Published: March 2003

Leukotriene receptor antagonists (LTRAs), such as montelukast and zafirlukast, have been demonstrated in a number of studies to possess bronchodilating and anti‐inflammatory properties, that make these drugs ideal candidates for the treatment of asthma. The last 1998‐updating of the GINA Guidelines for the diagnosis and therapy of asthma recommends the use of LTRAs in the treatment of moderate and mild asthma. In patients with moderate asthma not completely controlled with moderate doses of inhaled corticosteroids, the addition of a LTRA is indicated in alternative to either the increase of the inhaled corticosteroid dose or the addition of an inhaled long‐acting beta2‐agonist. Both in vitro and in vivo evidences indicate that LTRAs possess an anti‐inflammatory activity that is presumably complementary to that presented by corticosteroids. Moreover, clinical studies show that the addition of an LTRA, montelukast, is able to improve clinical and functional indexes in patients with asthma not controlled with inhaled corticosteroids, and to allow a reduction in corticosteroid dosage in patients with asthma well controlled by inhaled corticosteroids. In patients with mild persistent asthma monotherapy with an LTRA is indicated in alternative to a low‐dose inhaled corticosteroid, an inhaled cromone, or an oral slow‐release theophylline. Previous clinical studies in patients with mild to moderate asthma had demonstrated that monotherapy with LTRAs is able to improve airway function, asthma symptoms, use of as‐needed medications, exacerbation rate, and quality of life, without evidence of tolerance with prolonged use. Recently, in a subgroup analysis of patients with mild persistent asthma, a 6‐week treatment with oral montelukast or inhaled beclomethasone gave similar improvements in ‘rescue‐free’ days, days with well controlled asthma, FEV1, blood eosinophils, beta‐agonist use, and nocturnal awakes due to asthma.
Tuberculin responses in children with allergic diseases
Authors: Ozmen S. , Tomac N. , Uysal A. , Arslan Z. , Kuyucu N. , Yoney A.
Published: March 2003

Background: The prevalence of allergic disorders has been increasing over the last 30 years, especially in developed countries. One factor associated with this rise may be the decline of many childhood infections. We investigated tuberculin responses in allergic children in order to see the development of delayed‐type hypersensitivity reactions to tubercule bacillus infection.

Methods: The study sample was composed of 106 allergic and 100 nonallergic children vaccinated with bacille Calmette‐Guerin (BCG). The standard Mantoux test was applied to all children. The reactions were read after 72 h by measuring the diameter of the wheal.

Results: The wheal size was 6.29 ± 5.09 mm (mean ± SD) in allergic children, and 2.79 ± 2.96 mm in nonallergic children. The difference between the two groups was significant (P < 0.001). In children with a single BCG scar, the mean purified protein derivative (PPD) wheal size for allergic children was 4.77 ± 4.79 mm, and for nonallergic children it was 2.48 ± 3.19 mm. The mean PPD wheal sizes in allergic and nonallergic children who had been vaccinated twice were 8.35 ± 4.80 mm and 3.33 ± 2.44 mm, respectively. This difference was statistically significant (P < 0.05). In 27.35% of the allergic children and 6% of the nonallergic children, the positive tuberculin responses (PPD ≥ 10 mm) were recorded. The difference was significant (P < 0.05).

Conclusions: Our results showed that response to tuberculin in BCG‐immunized allergic children is higher than in BCG‐immunized nonallergic children.
Accurate determination of the number of CAG repeats in the Huntington disease gene using a sequence‐specific internal DNA standard
Authors: Bruland Ove , Almqvist Elisabeth W , Goldberg Y Paul , Boman Helge , Hayden Michael R , Knappskog Per M
Published: March 2003

We have developed a sequence‐specific internal DNA size standard for the accurate determination of the number of CAG repeats in the Huntington disease (HD) gene by cloning key fragments (between 15 and 64 CAG repeats) of the HD gene. These fragments, pooled to produce a sequence‐specific DNA ladder, enabled us to observe the true number of CAG repeats directly, with no need for calculations. Comparison of the calculated numbers of CAG repeats in the HD gene using this sequence‐specific DNA standard with a commercially available standard (GENESCAN‐500 TAMRA) showed that the latter underestimated the number of CAG repeats by three when analyzed by capillary electrophoresis on the ABI 310 Genetic Analyzer (POP4 polymer). In contrast, the use of the same standard overestimated the number of CAG repeats by one when the samples were analyzed by denaturing polyacrylamide electrophoresis on ABI 377 DNA Sequencer (6% denaturing polyacrylamide gel). This suggests that our sequence‐specific standard provides greater accuracy for the determination of the true number of CAG repeats in the HD gene than commercially available standards. The sequence‐specific standard can be radioactively labeled and successfully replace conventional DNA size standards when analyzing polymerase chain reaction (PCR)‐amplified HD alleles by denaturing polyacrylamide electrophoresis.
Recombinant proteins for genetic disease
Authors: Russell Chris S. , Clarke Lorne A.
Published: March 2003

The era of molecular biology has led to the development of powerful tools capable of generating therapeutics for genetic disorders. Although there is much current emphasis placed on the development of ‘gene therapy’ for human disease, developments in the production and availability of recombinant proteins are likely to have a more substantial impact on genetic disease in the short term. The clinical evaluation of recombinant or purified proteins serves as an initial ‘proof of principle’ of gene‐based therapies and thus should expedite advances in this area. Current examples include the use of bovine adenosine deaminase for a form of severe combined immune deficiency (SCID) (Hilman BC, Sorensen RU. Management options: SCIDS with adenosine deaminase deficiency. Ann Allergy 72: 1994: 395–403) and glucocerebrosidase for Gaucher disease (Niederau C, vom Dahl S, Haussinger D. First long‐term results of imiglucerase therapy of type 1 Gaucher disease. Eur J Med Res 1998: 3: 25–30). The success of these two enzyme replacement regimes in human clinical trials has been a main impetus for the development of gene‐based therapies for these disorders. The ‘molecularization of medicine’ has led to a more thorough understanding of the molecular basis of disease and disease pathogenesis. The availability of recombinant proteins and the development of appropriate delivery systems will result in more widespread use of these agents. Protein engineering will generate agents with novel functions as is already witnessed with the generation of fusion proteins. This review will highlight advances in the use of recombinant proteins for genetic disease and future potential uses of recombinant proteins.
Schizophrenia susceptibility gene locus at Xp22.3
Authors: Milunsky Jeff , Huang Xin‐Li , Wyandt Herman E , Milunsky Aubrey
Published: March 2003

Multiple genetic loci have been implicated in the search for schizophrenia susceptibility genes, none having been proven as causal. Genetic heterogeneity is probable in the polygenic etiology of schizophrenia. We report on two unrelated Caucasian women with paranoid schizophrenia (meeting Diagnostic and Statistical Manual of Mental Disorders (DSM IV) criteria) who have an Xp22.3 overlapping deletion characterized by fluorescence in situ hybridization (FISH). Patient 1 was previously reported by us (Wyandt HE, Bugeau‐Michaud L, Skare JC, Milunsky A. Partial duplication of Xp: a case report and review of previously reported cases. Amer J Med Genet 1991: 40: 280–283) to have a de novo partial duplication of Xp. At that time, she was a 24‐year‐old woman with short stature, irregular menses, other abnormalities suggestive of Turner syndrome, and paranoid schizophrenia. Recently, FISH analysis demonstrated that she has an inverted duplication (X)(p22.1p11.2) and a microscopic deletion (X)(p22.2p22.3) between DXS1233 and DXS7108 spanning approximately 16–18 cM. Patient 2 is a 14‐year‐old girl with short stature, learning disabilities, and paranoid schizophrenia. High‐resolution chromosome analysis revealed a de novo deletion involving Xp22. FISH analysis showed that the deletion (X)(p22.2p22.3) spanned 10–12 cM between AFMB290XG5 and DXS1060. Given that deletions of Xp22 are not common events, the occurrence of two unrelated schizophrenia patients with an overlapping deletion of this region would be extraordinarily rare. Hence, the deletion within Xp22.3 almost certainly contains a gene involved in the pathogenesis of paranoid schizophrenia.
STK11/LKB1 germline mutations are not identified in most Peutz–Jeghers syndrome patients
Authors: Jiang Cao‐Yang , Esufali Susmita , Berk Terri , Gallinger Steven , Cohen Zane , Tobi Martin , Redston Mark , Bapat Bharati
Published: March 2003

Germline mutations of the STK11 gene mapped to chromosome 19p13.3 are responsible for Peutz–Jeghers syndrome (PJS), a dominant disorder associated with characteristic gastrointestinal hamartomatous polyps and a predisposition to various cancers. We conducted a detailed investigation of germline STK11 alterations by protein truncation test and genomic DNA sequence analysis in ten unrelated PJS families. We identified a novel truncating deletion spanning STK11 exons 2–7 in a single patient and several known polymorphisms. Loss of heterozygosity studies in PJS polyps of four of these patients identified an allelic deletion of D19S886 in another patient. Our results suggest that STK11 mutations account for only a proportion of PJS cases.
Identification and characterization of ‐3c–g acceptor splice site mutation in human α‐ l‐iduronidase associated with mucopolysaccharidosis type IH/S
Authors: Teng Yn , Wang Tr , Hwu Wl , Lin Sp , Lee‐Chen Gj
Published: March 2003

DNA screening for mutations in the α‐ l‐iduronidase (IDUA) gene was performed in a Chinese mucopolysaccharidosis type IH/S patient. The patient had two different mutations: the maternal allele has L346R (t–g transversion in codon 346) and the paternal allele has 388‐3c–g (c–g transversion at position ‐3 of the 3′ splice site of intron 2). In transfected COS‐7 cells, L346R showed no appreciable IDUA activity (0.4% of normal activity), although it did not cause an apparent reduction in IDUA mRNA or protein level. The 388‐3c–g mutation profoundly affects normal splicing leading to a very unstable mRNA. Expression of the IDUA cDNA containing the mutated acceptor splice site showed trace amounts of enzyme activity (1.6% of normal activity). The results provide further support for the importance of cytosine at the ‐3 position in RNA processing.
The causes and consequences of random and non‐random X chromosome inactivation in humans
Authors: Brown CJ , Robinson WP
Published: March 2003

X chromosome (X) inactivation is a remarkable biological process including the choice and cis‐limited inactivation of one X, as well as the stable maintenance of this silencing by epigenetic chromatin alterations. The process results in females generally being mosaic for two populations of cells – one with each parental X active. In this review, we discuss recent advances in our understanding of how inactivation works, as well as the causes and clinical implications of deviations from random inactivation.
Exclusion of chromosome 15q21.1 in autosomal‐recessive Weill–Marchesani syndrome in an inbred Lebanese family
Authors: Mégarbané A , Mustapha M , Bleik J , Waked N , Delague V , Loiselet J
Published: March 2003

We report an inbred family where 3 siblings had short stature, brachydactyly, limitation of joint movements, microspherophakia, luxated lenses, glaucoma, and heart malformations. Parents of the affected siblings were relatively short, but did not have any of the other features present in their siblings. Those clinical features are consistent with the Weill–Marchesani syndrome (MIM 277600). Both autosomal‐recessive and autosomal‐dominant pedigrees have been reported, with a possible linkage to chromosome 15q21.1 in the latter. Linkage analysis at 15q21.1 in this Lebanese family allowed us to exclude the role of this region in the etiology of the syndrome. Speculations regarding the pathogenesis of the disorder are discussed.
Prenatal diagnosis and characterization of an unbalanced whole arm translocation resulting in monosomy for 18p
Authors: McGhee EM , Qu Y , Wohlferd MM , Goldberg JD , Norton ME , Cotter PD
Published: March 2003

Monosomy for the short arm of chromosome 18 is one of the most frequent autosomal deletions observed. While most cases result from terminal deletion of 18p, 16% of cases reported were as a result of an unbalanced whole arm translocation resulting in monosomy 18p. The origin and structure of these derivative chromosomes were reported in only a few cases. We report the prenatal diagnosis and characterization of a new case of monosomy 18p as a result of an unbalanced whole arm translocation. Amniocentesis was performed at 15 weeks of gestation on a 34‐year‐old woman initially referred for advanced maternal age. Holoprosencephaly was identified by ultrasound at the time of amniocentesis. Karyotype analysis showed an unbalanced whole arm translocation between the long arm of one chromosome 18 and the long arm of one chromosome 22, 45,XX,der(18;22)(q10;q10), in all metaphases. In effect, the fetus had monosomy for 18p. Parental karyotypes were normal, suggesting a de novo origin for the der(18;22). Fluorescence in situ hybridization (FISH) analysis was performed with α‐satellite probes D18Z1 and D14Z1/D22Z1 to identify the origin of the centromere on the der(18;22). Signal was observed with both probes, indicating that the centromere was composed of α‐satellite DNA from both constituent chromosomes. Genotyping of the fetus and her parents with chromosome 18p STS marker D18S391 showed only the paternal 187 bp allele was present in the fetus, indicating that it was the maternal chromosome 18 involved in the der(18;22). This case and previous reports show that de novo unbalanced whole arm translocations are more likely to retain α‐satellite sequences from the two chromosomes involved.
Recurrent mutations in the COL1A2 gene in patients with osteogenesis imperfecta
Authors: Trummer T , Brenner R , Just W , Vogel W , Kennerknecht I
Published: March 2003

A new recurrent point mutation in the COL1A2 gene was found in a patient with type III osteogenesis imperfecta (OI). A G‐to‐T transversion in nucleotide position 1121 leads to an amino acid substitution Gly238Cys. This is the first report on the most N‐terminal cysteine substitution in COL1A2 reported so far. Until now, at this position, only serine substitutions were observed five times in unrelated patients showing a highly variable expression of OI. It is obvious that endogenic and/or exogenic modifiers are involved in this classical autosomal dominant (or rarely recessive) mendelian disorder. An apparent preferential substitution by cysteine and serine residues is discussed with reference to post‐transcriptional or post‐translational collagen assembly control.
Apolipoprotein E polymorphism and lipid levels differ by gender and family history of diabetes: the Rancho Bernardo Study
Authors: Oh J‐Y , Barrett‐Connor E
Published: March 2003

Association between apolipoprotein E (apoE) gene polymorphism and lipid levels was studied in 164 nondiabetic first‐degree relatives of persons with diabetes and 962 nondiabetic persons with no family history of diabetes. Sex‐specific genotypic distribution of apoE polymorphism did not differ between persons with and without a family history of diabetes. In first‐degree relatives, lipid levels did not differ among persons with apoE2 (E2/2, E2/3), apoE3/3, and apoE4 (E4/4, E3/4) after adjusting for age, waist circumference, smoking, and alcohol and estrogen use. In persons without a family history of diabetes, both men (p<0.01) and women (p<0.001) with apoE2 showed lower levels of total and low density lipoprotein cholesterol compared with persons with apoE3/3 and apoE4. In women with a family history of diabetes, persons with apoE4 had larger waist circumference (p<0.05). ApoE2 allele is associated with more favorable levels of total and low density lipoprotein cholesterol in men and women without a family history of diabetes. ApoE4 allele is associated with obesity independent of dyslipidemia in women but not men with a family history of diabetes. ApoE polymorphism is not associated with lipids in men or women with a family history of diabetes.
Living with Marfan syndrome II. Medication adherence and physical activity modification
Authors: Peters KF , Horne R , Kong F , Francomano CA , Biesecker BB
Published: March 2003

We investigated the perceptions of and adherence to medication and physical activity guidelines in 174 adults with Marfan syndrome. Over 80% of those prescribed beta‐ and Ca2+‐channel blockade reportedly adhere well to their medication regimen. The presence of cardiovascular symptoms and fatigue were positively correlated with the medication use. Medication‐takers reported that they are psychologically receptive to the use of medication for prophylactic treatment of their cardiovascular problems. However, all do not view their medication as essential for their health. Duration of the medication regimen, type of medication, and perception of controllability of the condition were each independently associated with respondents’ perceptions of the necessity of taking beta‐ or Ca2+‐channel blockers. Over 80% of the respondents reported that they choose their physical activities with their diagnosis in mind. Modifying exercise activities was significantly correlated with an increased perception of Marfan syndrome as having negative consequences on the respondents’ lives. Genetic counseling should address beliefs about medication use and physical activity restrictions, as perceptions of these health behaviors may have significant impact on how adults with Marfan syndrome adhere to these recommendations and cope with their condition.