bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimization of codon usage is required for effective genetic immunization against Art v 1, the major allergen of mugwort pollen
Authors: Bauer R. , Himly M. , Dedic A. , Ferreira F. , Thalhamer J. , Hartl A. 
Published: September 2003

Background:  As the major allergen of mugwort pollen, Art v 1 is an important target for specific immunotherapy. However, both recombinant protein as well as a gene vaccine for Art v 1 failed to be immunogenic in mice. In order to improve immunogenicity we focused on genetic immunization because interspecific differences of codon usage have been shown as an obstacle for effective induction of immune responses with gene vaccines encoding infectious pathogens.Objective:  In order to find out, whether codon usage might also be used to improve genetic immunization with allergen genes, the response against a gene vaccine expressing the wild‐type gene of Art v 1 (pCMV‐wtArt) was compared with a synthetic codon‐optimized vector with human codon usage (pCMV‐humArt).Methods:  Balb/c mice were injected intradermally with pCMV‐wtArt or pCMV‐humArt. In vitro expression levels of both constructs were compared in transfection experiments. Total immunoglobulin G (IgG), IgG1, IgG2a and IgE antibodies were analyzed by enzyme‐linked immunosorbent assay and the anaphylactic activity of the sera was determined by allergen‐specific degranulation of rat basophil leukemia‐2H3 cells.Results:  No immune response was detectable with the gene vaccine expressing the wildtype Art v 1, but immunization with pCMV‐humArt revealed a strong and allergen‐specific induction of antibody responses. The antibodies recognized both the recombinant as well as the purified natural (glycosylated) Art v 1 molecule. The response type was Th1‐biased, as indicated by high levels of IgG2a antibodies. Expression analysis with B16 mouse melanoma cells transfected with pCMV‐humArt or pCMV‐wtArt revealed an impaired expression of the wild‐type vector but normal translation after recoding.Conclusion: The results demonstrate that optimization of codon usage offers a simple way to improve immunogenicity and therefore should be routinely considered in the development of gene vaccines for the treatment of allergy.
Interleukin (IL)‐4 and to a lesser extent either IL‐13 or interferon‐gamma regulate the production of eotaxin‐2/CCL24 in nasal polyps
Authors: Lezcano‐Meza D. , Dávila‐Dávila B. , Vega‐Miranda A. , Negrete‐García M. C. , Teran L. M. 
Published: September 2003

Background:  Eotaxin‐2/CCL24 is a potent eosinophil attractant that has been implicated in the recruitment of eosinophils in allergic disease. We have investigated whether the cytokines interleukin (IL)‐4, IL‐13, and interferon (IFN)‐gamma regulate eotaxin‐2/CCL24 in nasal polyps.Methods:  Nasal polyps were cultured in the presence of the cytokines described above and the concentration of eotaxin‐2/CCL24 was measured in the culture supernatant.Results:  IL‐4 was found to be the major stimulus for eotaxin‐2/CCL24 production from nasal polyps followed by IL‐13 and IFN‐gamma. IL‐4 induced eotaxin‐2/CCL24 in a dose‐dependent manner with concentrations as low as 0.1 ng/ml being able to induce eotaxin‐2/CCL24. By immunohistochemistry, eotaxin‐2/CCL24 immunoreactivity was localized to mononuclear cells in the IL‐4 stimulated nasal polyp tissue. Interestingly, nasal turbinates obtained from patients suffering from nonallergic rhinitis (vasomotor rhinitis) were also found to release eotaxin‐2/CCL24 both spontaneously and following cytokine stimulation with IL‐4 and IFN‐gamma being major inducers of this cytokine.Conclusions:  All together these findings suggest that Th1 and Th2 cytokines may regulate eotaxin‐2/CCL24 production in nasal polyps and nonallergic rhinits.
Allergen‐dependent CD14 modulation and apoptosis in monocytes from allergic patients
Authors: Monteseirín J. , Bonilla I. , Chacón P. , Vega A. , Camacho M. J. , Guardia P. , Conde J. , Sobrino F. 
Published: September 2003

Background: CD14 is a most important monocyte surface molecule. Recently, it has been reported that there is an important relationship between CD14 and immunoglobulin E, and that regulation of CD14 expression is an effector mechanism mediating apoptosis of monocytes.Objective: The present study was designed to determine whether specific allergens were able to modulate CD14 expression and apoptosis by monocytes from allergic patients or whether specific immunotherapy (IT) might affect these processes.Methods: One group of adult allergic asthmatic patients had received IT for the previous 3 years. Another similar group was not treated with IT. We challenged peripheral blood monocytes from both groups of asthmatic patients in vitro with the specific allergen that produced clinical symptoms in asthmatic patients. The cells were also challenged with allergen to which the patients were not sensitive. Monocytes from normal subjects were also challenged with allergens. Expression of CD14 on the monocyte surface was analyzed by flow cytometry, and soluble CD14 (sCD14) in culture supernatant by enzyme‐linked immunosorbent assay. The three groups of subjects were challenged with allergens, and apoptosis was analyzed by flow cytometry.Results: When monocytes from non‐IT‐treated asthmatic patients were cultivated with the allergens to which the patients were sensitive, a significant up‐regulation on the monocyte surface was observed compared with results from the healthy group (P < 0.003) and from the IT asthmatic group (P < 0.003). A significantly higher sCD14 level was observed in the culture supernatant of the monocytes from the IT asthmatic group were observed compared with those from the healthy group (P < 0.001) and those from the non‐IT asthmatic group (P < 0.001). A significantly higher apoptosis level was observed in monocytes from the IT asthmatic group compared with those from the healthy group (P < 0.001) and those from the non‐IT asthmatic group (<0.001).Conclusions: We present evidence that the expression of CD14 on the surface of monocytes and the apoptosis of the same cells can be modulated by an allergen‐dependent mechanism. These processes can be affected by IT.
Human serum IgE‐mediated mast cell degranulation shows poor correlation to allergen‐specific IgE content
Authors: Marchand F. , Mecheri S. , Guilloux L. , Iannascoli B. , Weyer A. , Blank U. 
Published: September 2003

Background:  Although allergen‐specific IgE content in serum can be determined immunochemically, little is known about the relationship between this parameter and the strength of the degranulation response upon allergen triggering.Objectives:  Analyse the degranulation capacity of immunochemically defined purified and serum IgE after challenge with anti‐IgE or allergen using a rat mast cell line (RBL) transfected with the α‐chain of the human high‐affinity IgE receptor (FcɛRI).Methods:  Purified IgE specific for 4‐hydroxy‐3nitrophenylacetyl, purified IgE of unknown specificity, and sera from allergic patients sensitive to Dermatophagoides pteronyssinus and Dactylis glomerata were assessed. Degranulation was measured by a β‐hexosaminidase release assay after anti‐IgE or allergen‐specific challenge.Results:  For purified monoclonal IgE a significant correlation (r = 0.97) was found between the proportion of bound allergen‐specific IgE and the strength of the degranulation response. In contrast, no correlation (r = 0.27) was detected after sensitization with serum IgE.Conclusion:  Our studies demonstrate that mast cell activation mediated through IgE from allergic patients is a result of complex relationships that are not only dependent on allergen‐specific IgE content but also relate to the capacity to efficiently sensitize and trigger the signalling responses that lead to degranulation.
Prevalence of asthma with aspirin hypersensitivity in the adult population of Poland
Authors: Kasper L. , Sladek K. , Duplaga M. , Bochenek G. , Liebhart J. , Gladysz U. , Malolepszy J. , Szczeklik A. 
Published: September 2003

Background: Acetylsalicylic acid (ASA) and other nonsteroid anti‐inflammatory drugs (NSAIDs) are reported to account for 21–25% of all adverse drug reactions. Some asthmatics may react to ASA and other NSAIDs with acute bronchoconstriction, profuse rhinorrhea and skin flushing. This is a distinct clinical syndrome called aspirin‐induced asthma (AIA). The prevalence of AIA among asthmatic patients in Poland has not been previously assessed.Methods: A questionnaire survey of 12 970 adults of both sexes, randomly selected from the population of Poland.Results: The prevalence of AIA in the general population of Poland was estimated as 0.6%. Thirty patients (4.3%; 95% CI: 2.8–5.8) of 703 asthmatics (5.4% of general population) reported symptoms attesting to hypersensitivity to aspirin. In 27% of them the reactions were precipitated by aspirin, whereas in the remaining subjects by other NSAIDs.Conclusions: The prevalence of AIA in Poland is 4.3%, being somewhat lower than in Finland and Australia, where it was recently reported to account for 8.8 and 10.9% of the adult asthmatics, respectively. These figures indicate that aspirin hypersensitivity might be a significant community problem.
Serum inhibitors for human mast cell growth: possible role of retinol
Authors: Ishida S. , Kinoshita T. , Sugawara N. , Yamashita T. , Koike K. 
Published: September 2003

Background: In vitro culture systems have been used to study the physiological and pathological characteristics of human mast cells. However, there are some differences in proliferation and maturation of mast cells between fetal bovine serum (FBS)‐containing and serum‐deprived cultures. Accordingly, we attempted to identify circulating factor(s) affecting the development of human mast cells.Methods: We measured the serum levels of retinol and several cytokines. To elucidate the antiproliferative effects of the serum, a retinoic acid receptor (RARα) antagonist and neutralizing antibodies against cytokines were used.Results: Similar to FBS, human serum dose‐dependently suppressed the growth of tryptase+ cells from CD34+ cord blood cells or 20‐week cultured mast cells under stimulation with stem cell factor (SCF). The serum‐mediated inhibition might be based on a decline in proliferation rate. Among inhibitors for mast cell growth, retinol and transforming growth factor (TGF)‐β1 were present at high levels in human serum. In contrast with anti‐TGF‐β1 antibody, an RARα antagonist counteracted the serum‐induced suppression of human mast cell proliferation.Conclusions: Our results suggest that retinol and its derivatives act as a circulating regulator for human mast cell growth. The RARα antagonist may be a useful tool to obtain higher numbers of mast cells in FBS‐containing cultures.
Two CD14 promoter polymorphisms and atopic phenotypes in Czech patients with IgE‐mediated allergy
Authors: Bučková D. , Hollá L. I. , Schüller M. , Znojil V. , Vácha J. 
Published: September 2003

Background: Immunoglobulin E (IgE)‐mediated allergy belongs to common chronic disorders resulting from an interaction between both genetic and environmental factors. The gene encoding CD14 is a positional candidate gene for allergic diseases as it is localized on chromosome 5q31.1, a region that is linked to asthma and bronchial hyperresponsiveness. Recently, several polymorphisms in the promoter region of this gene have been associated with atopic phenotypes in various populations.Methods: We investigated relationship among atopic phenotypes and two polymorphisms [C(‐159)T and G(‐1359)T] in the promoter of the CD14 gene in the Czech population. Polymerase chain reaction with restriction fragment length polymorphism analyses was used to determine the CD14 genotypes in subjects with IgE‐mediated allergic diseases (n = 562) and random controls (n = 320).Results: The CD14 allele or genotype distributions were similar in patients and control group. However, the frequency of the C allele of the C(‐159)T polymorphism was higher in patients with positive skin prick tests for moulds than in patients without reactivity to this antigen (P < 0.002, Pcorr<0.01). In addition, we found that patients with homozygous genotype (GG) of the G(‐1359)T polymorphism had marginally lower percentage of positive skin prick tests compared with the other genotypes (P < 0.029, Pcorr > 0.05).Conclusions: Our study supports the idea that CD14 gene variants may act as disease modifiers of IgE‐mediated allergic diseases.
Childhood asthma and continuous exposure to cats since the first year of life with cats allowed in the child's bedroom
Authors: Oberle D. , von Mutius E. , von Kries R. 
Published: September 2003

Background: There are controversial data as to interdependencies of exposure to furred pets in infancy and the prevalence of asthma and hay fever in children. Does the timing, intensity and type of pet exposure matter?Methods: Cross‐sectional questionnaire data on 8216 German schoolchildren aged 5–7 years not living on a farm in ten rural districts in Bavaria in 1997 were analysed. The diagnosis of asthma and hay fever was ascertained with the International Study of Asthma and Allergies in Childhood (ISAAC) core questions. Wheeze and asthma were classified as ‘atopic’ in children who also had hay fever or atopic dermatitis. Prevalence and intensity of exposure to pets in the first year of life and at present were assessed via questionnaire.Results: Although the study was of considerable size we found no convincing association between atopic disease and pet exposure in general. Exposure to cats from the first year of life to school entry, however, was associated with a reduced prevalence of atopic asthma, if cats were allowed to be in the child's bedroom: no case of atopic asthma in 296 children exposed and an aOR 0.11 (95% CI:0.01–0.52) for atopic wheeze in the last 12 months.Conclusions: Allowing cats to be in the child's bedroom from the first year of life onwards may be an indicator of intensive exposure to cats and appears to prevent the development of childhood asthma.
Maternal smoking in pregnancy alters neonatal cytokine responses
Authors: Noakes P. S. , Holt P. G. , Prescott S. L. 
Published: September 2003

Background: Maternal cigarette smoking in pregnancy is an important, common and avoidable exposure that has been linked with elevated cord blood (CB) immunoglobulin E levels and subsequent asthma and allergic disease in childhood. Despite this, there is still very little information about the immunological effects of maternal smoking on the fetus.Methods: This aim of this study was to compare cord blood mononuclear cell (CBMC) cytokine responses to allergens [ovalbumin (OVA) or house dust mite (HDM)] and mitogens [concanavalin A (ConA) or phytohemaglutinen (PHA)] in neonates whose mothers smoked throughout pregnancy (n = 17) with responses of neonates whose mothers never smoked (n = 40). Cell cultures were stimulated for 24 h and supernatants collected for cytokine detection by enzyme‐linked immunosorbent assay [interleukin (IL)‐13, IL‐6, interferon (IFN)γ and IL‐10]. Cell pellets were also collected for cytokine mRNA detection (IL‐5, IL‐9, IFNγ).Results: Maternal smoking in pregnancy was associated with significantly higher neonatal T helper type 2 (IL‐13 protein) responses to both HDM (P = 0.01) and OVA (P = 0.035). These effects remained statistically significant after allowing for confounding factors, including the effects of maternal atopy. Similar trends were also seen for IL‐9mRNA, IL‐5mRNA and IL‐6 responses, although these were not statistically significant. Although IFNγ mRNA responses to PHA (P = 0.015) and ConA (P = 0.025) were lower if mothers smoked in pregnancy, there were no differences in neonatal (Th1) IFNγ protein responses to allergens or mitogens.Conclusions: These findings indicate that maternal cigarette smoking can modify aspects of fetal immune function and highlight the need for further studies in this area.
Small vulvar squamous cell carcinomas and adjacent tissues. A morphologic study
Authors: POULSEN HEMMING , JUNGE JETTE , VYBERG MOGENS , HORN THOMAS , LUNDVALL FINN 
Published: September 2003

Vulvar squamous cell carcinomas are of different subtypes and degrees of differentiation, and may be associated with adjacent lichen sclerosus and/or varying degrees of dysplasia. The aim of this investigation was to study small carcinomas with a diameter of less than 2 cm in order to find a possible relation between subtypes of carcinomas and adjacent epithelial changes.Fourteen cases of small vulvar squamous cell carcinomas were totally embedded in paraffin. Serial sectioning made a detailed mapping of all different lesions possible, and a two‐ and three‐dimensional imaging was obtained in each case.Seven patients with keratinizing squamous cell carcinomas (median age 65) had adjacent lichen sclerosus. All carcinomas were completely surrounded by areas of VIN1. VIN2 and VIN3 were not found. Seven patients without lichen sclerosus (median age 58) showed squamous cell carcinomas of the keratinizing type (n=2) or the basaloid type (n=5). Five of these cases were incompletely surrounded by varying degrees of dysplasia, mainly VIN2 and VIN3.Two different pathogenetic pathways for the development of vulvar squamous cell carcinoma are likely.
Analysis of protein tyrosine kinase expression in melanocytic lesions by tissue array
Authors: Shen Steven S. , Zhang Peter S. , Eton Omar , Prieto Victor G. 
Published: September 2003

Background:  It has been proposed that melanoma progression involves a multistep process from benign nevi (BN), dysplastic nevi (DN), radial and vertical growth phase melanoma (MM) to metastatic melanoma (MMM). Protein tyrosine kinases (PTKs) may participate in this progression.Methods:  Tissue microarray blocks of 89 melanocytic lesions were evaluated by immunohistochemistry for the expression of selected PTKs: c‐kit, c‐abl, abl‐related gene (ARG), platelet‐derived growth factor receptors α (PDGFR‐α) and β (PDGFR‐β).Results:  Seventeen of 31 (55%) MMM lacked expression of c‐kit versus 100% expression (18/18) in DN and 96% expression (22/23) in MM; similarly, only 59% (10/17) of BN showed expression of c‐kit. PDGFR‐β expression levels were similar in BN, DN, and MM, but lower in MMM. There was a trend toward lower expression of abl and ARG from BN to MMM. There was a marked decrease in staining intensity of ARG from BN to DN, MM, and MMM.Conclusion:  Our results support that BN is different from DN and MM and that these two are different from MMM. Metastasis appears to be associated with loss of c‐kit and PDGFR‐β expression. Since malignant melanoma expresses PTK, it may be a candidate for treatment with anti‐PTK, such as STI‐571 (Gleevec).
Scarring alopecia associated with mastocytosis
Authors: Xu Xiaowei , Solky Benjamin , Elenitsas Rosalie , Cotsarelis George 
Published: September 2003

Background:  Mastocytosis is comprised of a group of heterogeneous diseases involving various organs. Urticaria pigmentosa is the most common manifestation of cutaneous mastocytosis; others include mastocytoma, diffuse mastocytosis, and telangiectasia macularis eruptiva perstans.Methods:  We describe a case of indolent mastocytosis presenting as scarring alopecia. The scalp biopsy revealed a perifollicular and dermal inflammatory infiltrate composed predominantly of mast cells, which was confirmed by tryptase and Giemsa stains.Results:  The preponderance of mast cells in the biopsy prompted testing for urine N‐methylhistamine levels, which were elevated and confirmed the diagnosis of mastocytosis. This is the first report of mastocytosis presenting as scarring alopecia.Conclusions:  This case suggests that the diagnosis of mastocytosis should be entertained in patients presenting with scarring alopecia accompanied by an intense mast cell infiltrate on scalp biopsy and also supports the notion that mast cells may be involved in the pathogenesis of alopecia.
Myxoid Spitz nevus
Authors: Hoang Mai P. 
Published: September 2003

Background:  The deposition of extracellular mucin has not been described in Spitz nevus and herein such a case is reported.Methods:  A 6‐year‐old male presented with a growing 1.0‐cm pigmented lesion on his left anterior knee. The lesion was excised.Results:  The histologic sections demonstrated a symmetrical and dome‐shaped proliferation of spindle and epithelioid melanocytes with sharp lateral demarcation at the dermal–epidermal junction and within the superficial dermis. Features of Spitz nevus such as retraction from the epidermis, eosinophilic bodies, and uniform cytologic atypia were seen. Of interest, there was marked mucin deposition within the epidermal clefts and between the neoplastic cells.The mucin was highlighted by alcian blue and colloidal iron stains, and it was negative with mucicarmine and periodic acid–Schiff stains.Conclusion:  Awareness that soitz nevi can rarely have extracellular mucin helps in avoiding diagnostic pitfalls.
Subungual pleomorphic fibroma
Authors: Hsieh Ya‐Ju , Lin Yang‐Chih , Wu Yu‐Hung , Su Hsin‐Yi , Billings Steven D. , Hood Antoinette F. 
Published: September 2003

Background:  Pleomorphic fibroma is a benign fibroblastic tumor characterized by pleomorphic, hyperchromatic cells or giant multinucleated cells embedded in a collagenous stroma. These cytologic features may lead to an incorrect diagnosis of malignancy. Most cases reported in the literature are located on trunk or extremities; the presentation as a subungual mass is rare.Methods:  We report an unusual case of a subungual pleomorphic fibroma in 66‐year‐old woman. Clinical information was obtained. Histologic examination and immunohistochemical studies were performed.Results:  A 66‐year‐old woman presented with a longstanding (40 years), subungual mass that deformed the nail of the left middle finger. Microscopic examination revealed a paucicellular tumor composed of hyperchromatic spindled, pleomorphic, floret‐like giant cells embedded in haphazardly arranged collagen bundles in the dermis. No mitotic figures were seen. The tumor cells were vimentin‐positive but did not stain with antibodies to S‐100, cytokeratin, smooth muscle actin, factor XIIIa or CD34 negative. The diagnosis of a pleomorphic fibroma was made. Follow‐up shows no evidence of tumor, 36 months after excision.Conclusion:  Pleomorphic fibroma of the subungual region is an unusual cutaneous tumor with histologic features that may cause confusion with true sarcomas. This is only the second case reported of a subungual pleomorphic fibroma. Pleomorphic fibroma should be considered in the differential diagnosis of pleomorphic subungual tumors.
Chronic vulvar purpura: persistent pigmented purpuric dermatitis (lichen aureus) of the vulva or plasma cell (Zoon's) vulvitis?
Authors: Li Qing , Leopold Kathy , Carlson J. Andrew 
Published: September 2003

Background:  Lichen aureus is localized variant of persistent pigmented purpuric dermatitis that typically affects the legs and can be associated with delayed hypersensitivity reactions or vascular abnormalities. Plasma cell vulvitis (Zoon's vulvitis) is a rare condition that frequently contains hemosiderin deposits and is suspected to be a mucosal reaction pattern due to variety of insults, most often local irritation or trauma.Case Report:  A 50‐year‐old female with longstanding complaints of spotting, vulvar dryness, irritation, and dyspareunia presented with circumscribed, purpuric, erythematous vulvar patches. Past estrogen cream treatment evoked symptoms of discomfort. On biopsy, siderophages and extravasated red blood cells were found in conjunction with a lichenoid, lymphocyte and plasma cell infiltrate, and dilated dermal and intraepithelial vessels.Conclusions:  Reported herein is an unusual vulvar dermatosis that is best classified as a localized variant of persistent pigmented dermatosis (lichen aureus) but overlaps clinically and histologically with Zoon's vulvitis. This constellation of findings may represent a site‐specific mucosal reaction to an erosive process that could either be inflammatory (hypersensitivity reaction) and/or traumatic in nature.