bluuebunny/crossref_metadata_2025 huggingface dataset:
Elevated neutrophil membrane expression of proteinase 3 is dependent upon CD177 expression
Authors: Abdgawad M , Gunnarsson L , Bengtsson A A , Geborek P , Nilsson L , Segelmark M , Hellmark T
Published: May 2010

Proteinase 3 (PR3) is a major autoantigen in anti-neutrophil cytoplasmic antibodies (ANCA)-associated systemic vasculitis (AASV), and the proportion of neutrophils expressing PR3 on their membrane (mPR3+) is increased in AASV. We have shown recently that mPR3 and CD177 are expressed on the same cells in healthy individuals. In this study we try to elucidate mechanisms behind the increased mPR3 expression in AASV and its relationship to CD177. All neutrophils in all individuals were either double-positive or double-negative for mPR3 and CD177. The proportion of double-positive neutrophils was increased significantly in AASV and systemic lupus erythematosus patients. The proportion of mPR3+/CD177+ cells was not correlated to general inflammation, renal function, age, sex, drug treatment and levels of circulating PR3. AASV patients had normal levels of granulocyte colony-stimulating factor and granulocyte–macrophage colony-stimulating factor. Pro-PR3 was found to constitute 10% of circulating PR3 but none of the mPR3. We found increased mRNA levels of both PR3 and CD177 in AASV, but they did not correlate with the proportion of double-positive cells. In cells sorted based on membrane expression, CD177–mRNA was several-fold higher in mPR3+ cells. When exogenous PR3 was added to CD177-transfected U937 cells, only CD177+ cells bound PR3 to their membrane. In conclusion, the increased membrane expression of PR3 found in AASV is not linked directly to circulating PR3 or PR3 gene transcription, but is dependent upon CD177 expression and correlated with the transcription of the CD177 gene.
The immunotherapeutic potential of dendritic cells in type 1 diabetes
Authors: Mukherjee G , DiLorenzo T P
Published: May 2010

Type 1 diabetes is an autoimmune disease characterized by destruction of the pancreatic islet beta cells that is mediated primarily by T cells specific for beta cell antigens. Insulin administration prolongs the life of affected individuals, but often fails to prevent the serious complications that decrease quality of life and result in significant morbidity and mortality. Thus, new strategies for the prevention and treatment of this disease are warranted. Given the important role of dendritic cells (DCs) in the establishment of peripheral T cell tolerance, DC-based strategies are a rational and exciting avenue of exploration. DCs employ a diverse arsenal to maintain tolerance, including the induction of T cell deletion or anergy and the generation and expansion of regulatory T cell populations. Here we review DC-based immunotherapeutic approaches to type 1 diabetes, most of which have been employed in non-obese diabetic (NOD) mice or other murine models of the disease. These strategies include administration of in vitro-generated DCs, deliberate exposure of DCs to antigens before transfer and the targeting of antigens to DCs in vivo. Although remarkable results have often been obtained in these model systems, the challenge now is to translate DC-based immunotherapeutic strategies to humans, while at the same time minimizing the potential for global immunosuppression or exacerbation of autoimmune responses. In this review, we have devoted considerable attention to antigen-specific DC-based approaches, as results from murine models suggest that they have the potential to result in regulatory T cell populations capable of both preventing and reversing type 1 diabetes.
TP53 mutations coincide with the ectopic expression of activation-induced cytidine deaminase in the fibroblast-like synoviocytes derived from a fraction of patients with rheumatoid arthritis
Authors: Igarashi H , Hashimoto J , Tomita T , Yoshikawa H , Ishihara K
Published: May 2010

Main features of rheumatoid arthritis (RA), hyperplasia of fibroblast-like synoviocytes (FLS) and joint destruction are caused by inflammatory cytokines produced in chronic autoimmune inflammation. Cell-intrinsic acquisition of tumour-like phenotypes of RA-FLS could also be responsible for the aggressive proliferation and invasion, which are supported by the fact that in some cases RA-FLS has mutations of a tumour suppressor gene TP53. However, the underlying molecular mechanism for TP53 mutations in RA-FLS has not yet been clarified. Recently it has been reported that the non-lymphoid cells in the inflammatory tissues express ectopically the activation-induced cytidine deaminase (AID) gene that induces somatic hypermutations, not only at the immunoglobulin (Ig) gene variable regions in germinal centre B lymphocytes but also at coding regions in TP53. Real-time polymerase chain reaction (PCR) analyses revealed more than half (five of nine) of the RA-FLS lines we established showed the markedly increased expression of AID. AID transcription in RA-FLS was augmented by tumour necrosis factor (TNF)-α and even by physiological concentration of β-oestradiol that could not induce AID transcription in osteoarthritis-FLS. Furthermore, AID-positive RA-FLS presented a higher frequency of somatic mutations in TP53. Cytological and immunohistochemical analyses demonstrated clearly the ectopic expression of AID in the FLS at the RA synovium. These data suggested strongly a novel consequence of RA; the ectopic expression of AID in RA-FLS causes the somatic mutations and dysfunction of TP53, leading to acquisition of tumour-like properties by RA-FLS.
Presence of intestinal helminths decreases T helper type 1 responses in tuberculoid leprosy patients and may increase the risk for multi-bacillary leprosy
Authors: Diniz L M , Magalhães E F L , Pereira F E L , Dietze R , Ribeiro-Rodrigues R
Published: May 2010

Resistance to intracellular pathogens such as Mycobacterium leprae is dependent upon an effective T helper type 1 (Th1)-type immune response. On the other hand, intestinal helminths are known to subvert the host's immune response towards to either a Th2-type immune response or a regulatory T cell up-regulation, which may affect the host's ability to mount an effective response to mycobacteria. Here, we report a significant association between intestinal helminth infections and lepromatous leprosy [odds ratio (OR), 10·88; confidence interval (CI) 95%: 4·02–29·4; P < 0·001]. We also observed that the frequency of intestinal helminths correlated strongly with the mycobacterial index (r = 0·982, P < 0·01). Corroborating with our hypothesis, intracellular levels of interferon-γ were decreased significantly in leprosy patients co-infected with intestinal helminths when compared to leprosy patients without worms. Conversely, lepromatous leprosy patients with intestinal worms produced higher levels of both interleukin (IL)-4 and IL-10. Our results suggest that a pre-existing infection by intestinal helminths may facilitate the establishment of M. leprae infection or its progression to more severe forms of leprosy.
A crucial role of sialidase Neu1 in hyaluronan receptor function of CD44 in T helper type 2-mediated airway inflammation of murine acute asthmatic model
Authors: Katoh S , Maeda S , Fukuoka H , Wada T , Moriya S , Mori A , Yamaguchi K , Senda S , Miyagi T
Published: May 2010

CD44 is a highly glycosylated cell adhesion molecule that is involved in lymphocyte infiltration of inflamed tissues. We have demonstrated previously that sialic acid residues of CD44 negatively regulates its receptor function and CD44 plays an important role in the accumulation of T helper type 2 (Th2) cells in the airway of a murine model of acute asthma. Here we evaluated the role of sialidase in the hyaluronic acid (HA) receptor function of CD44 expressed on CD4+ T cells, as well as in the development of a mite antigen-induced murine model of acute asthma. Splenic CD4+ T cell binding of HA was examined with flow cytometry. Expression of sialidases (Neu1, Neu2, Neu3 and Neu4) in spleen cells was evaluated by quantitative real-time reverse transcription–polymerase chain reaction. Airway inflammation and airway hyperresponsiveness (AHR) were evaluated in the asthmatic Neu1-deficient mouse strain SM/J model. Splenic CD4+ T cells from asthmatic model mice displayed increased HA receptor activity of CD44 after culture with the antigen, along with characteristic parallel induction of sialidase (Neu1) expression. This induction of HA binding was suppressed significantly by a sialidase inhibitor and was not observed in SM/J mice. Th2 cytokine concentration and absolute number of Th2 cells in the bronchoalveolar lavage fluid, and AHR were decreased in SM/J mice. In conclusion, HA receptor activity of CD44 and acute asthmatic reactions, including Th2-mediated airway inflammation and AHR, are dependent upon Neu1 enzymatic activity. Our observation suggests that Neu1 may be a target molecule for the treatment of asthma.
In vivo manipulation of Vγ9Vδ2 T cells with zoledronate and low-dose interleukin-2 for immunotherapy of advanced breast cancer patients
Authors: Meraviglia S , Eberl M , Vermijlen D , Todaro M , Buccheri S , Cicero G , La Mendola C , Guggino G , D'Asaro M , Orlando V , Scarpa F , Roberts A , Caccamo N , Stassi G , Dieli F , Hayday A C
Published: May 2010

The potent anti-tumour activities of γδ T cells have prompted the development of protocols in which γδ-agonists are administered to cancer patients. Encouraging results from small Phase I trials have fuelled efforts to characterize more clearly the application of this approach to unmet clinical needs such as metastatic carcinoma. To examine this approach in breast cancer, a Phase I trial was conducted in which zoledronate, a Vγ9Vδ2 T cell agonist, plus low-dose interleukin (IL)-2 were administered to 10 therapeutically terminal, advanced metastatic breast cancer patients. Treatment was well tolerated and promoted the effector maturation of Vγ9Vδ2 T cells in all patients. However, a statistically significant correlation of clinical outcome with peripheral Vγ9Vδ2 T cell numbers emerged, as seven patients who failed to sustain Vγ9Vδ2 T cells showed progressive clinical deterioration, while three patients who sustained robust peripheral Vγ9Vδ2 cell populations showed declining CA15-3 levels and displayed one instance of partial remission and two of stable disease, respectively. In the context of an earlier trial in prostate cancer, these data emphasize the strong linkage of Vγ9Vδ2 T cell status to reduced carcinoma progression, and suggest that zoledronate plus low-dose IL-2 offers a novel, safe and feasible approach to enhance this in a subset of treatment-refractory patients with advanced breast cancer.
Plant dispersal by teal (Anas crecca) in the Camargue: duck guts are more important than their feet
Authors: BROCHET A. L. , GUILLEMAIN M. , FRITZ H. , GAUTHIER‐CLERC M. , GREEN A. J.
Published: May 2010

1. Migratory waterbirds are major vectors for the dispersal of aquatic plants. However, quantitative field studies of the frequency of transport are scarce, and the relative importance of internal and external transport remains unclear.

2. We quantified and compared the rates of internal and external transport of aquatic plant propagules by teal (Anas crecca) in the Camargue (southern France), inspecting the lower gut contents of birds that had been shot (n = 366) and washing birds that had been live‐trapped (n = 68) during the winters of 2006–2007 and 2007–2008.

3. Intact propagules (n = 902) of 21 plant taxa were recorded in the rectum of teal, of which 16 germinated or were shown to be viable. Intact propagules were recorded in the rectum of 20% of teal, with up to 171 propagules per individual bird. Chara oogonia were most abundant (60% of intact propagules), suggesting that small size favours internal transport. Eleocharis palustris, Juncus spp. and Potamogeton pusillus (17, 7 and 6% of intact propagules, respectively) were also very abundant.

4. Intact propagules (n = 12) of 10 plant taxa were found on the outside of live teal, and four of these taxa later germinated. Intact propagules were found on 18% of teal. No teal was found to carry more than one propagule externally. There was no difference in size between propagules transported internally and externally.

5. Teal are major dispersers of plants within the Camargue, despite being highly granivorous. Contrary to widespread assumptions in the literature, endozoochory by ducks appears to be a much more important mode of dispersal for aquatic plants than exozoochory. We found no evidence of changes in the probability of plant propagule dispersal at a landscape scale over the course of the winter, so propagule production and zoochory appear to be decoupled over time in aquatic systems.
High content cellular immune profiling reveals differences between rhesus monkeys and men
Authors: Magalhaes Isabelle , Vudattu Nalini K. , Ahmed Raija K. , Kühlmann‐Berenzon Sharon , Ngo Yen , Sizemore Donata R. , Wehlin Lena , Weichold Frank , Andersson Jan , Skeiky Yasir A.W. , Sadoff Jerry , Gaines Hans , Thorstensson Rigmor , Spångberg Mats , Maeurer Markus J.
Published: May 2010

A better understanding of similarities and differences in the composition of the cellular immune system in non‐human primates (NHPs) compared with human subjects will improve the interpretation of preclinical studies. It will also aid in addressing the usefulness of NHPs as subjects for studying chronic diseases, vaccine development and immune reconstitution. We employed high content colour flow cytometry and analysed simultaneously the expression of CD3, CD4, CD8α, CD8β, CD16/CD56, CD45RA, CCR7, CD27, CD28, CD107a and the interleukin‐7 receptor α‐chain (IL‐7Rα) in peripheral blood mononuclear cells (PBMCs) of 27 rhesus macaques and 16 healthy human subjects. Regulatory T cells (Tregs) were identified using anti‐CD3, ‐CD4, ‐CD25, ‐FoxP3, and ‐IL‐7Rα monoclonal antibodies. Responsiveness to IL‐7 was gauged in a signal transducer and activation of transcription 5 (STAT‐5) phosphorylation assay. Human and NHP PBMCs showed a similar T‐cell composition pattern with some remarkable differences. Similarities: human and NHP CD4+ and CD8+ cells showed a similar STAT‐5 phosphorylation pattern in response to IL‐7. Multicolour flow cytometric analysis identified a CD4+ CD8αα+ CD8αβ+ T‐cell population in NHPs as well as in human subjects that expressed the degranulation marker CD107a and may represent a unique CD4+ T‐cell subset endowed with cytotoxic capacity. Differences: we identified in PBMCs from NHPs a higher proportion (5·16% in CD3+ T cells) of CD8αα+ T cells when compared with human donors (1·22% in CD3+ T cells). NHP CD8αα+ T cells produced tumour necrosis factor‐α / interferon‐γ (TNF‐α/IFN‐γ) or TNF‐α, whereas human CD8αα+ T cells produced simultaneously TNF‐α/IFN‐γ and IL‐2. A minor percentage of human CD8+ T cells expressed CD25bright and FoxP3 (0·01%). In contrast, 0·07% of NHP CD8+ T cells exhibited the CD25bright FoxP3+ phenotype. PBMCs from NHPs showed less IL‐7Rα‐positive events in all T‐cell subsets including CD4+ Tregs (median 5%) as compared with human (median 12%). The data visualize commonalities and differences in immune cell subsets in humans and NHPs, most of them in long‐lived memory cells and cells with suppressive functions. This provides a matrix to assess future efforts to study diseases and vaccines in NHPs.
Interleukin (IL)‐21‐independent pathogen‐specific CD8+ T‐cell expansion, and IL‐21‐dependent suppression of CD4+ T‐cell IL‐17 production
Authors: Ertelt James M. , Johanns Tanner M. , Rowe Jared H. , Way Sing Sing
Published: May 2010

Although interleukin‐21 (IL‐21) potently activates and controls the differentiation of immune cells after stimulation in vitro, the role for this pleiotropic cytokine during in vivo infection remains poorly defined. Herein, the requirement for IL‐21 in innate and adaptive host defence after Listeria monocytogenes infection was examined. In the innate phase, IL‐21 deficiency did not cause significant defects in infection susceptibility, or in the early activation of natural killer and T cells. In the adaptive phase, L. monocytogenes‐specific CD8+ T cells expand to a similar magnitude in IL‐21‐deficient mice compared with control mice. Interestingly, the IL‐21‐independent expansion of L. monocytogenes‐specific CD8+ T cells was maintained even in the combined absence of IL‐12 and type I interferon (IFN) receptor. Similarly, L. monocytogenes‐specific CD4+ T cells expanded and produced similar levels of IFN‐γ regardless of IL‐21 deficiency. Unexpectedly however, IL‐21 deficiency caused significantly increased CD4+ T‐cell IL‐17 production, and this effect became even more pronounced after L. monocytogenes infection in mice with combined defects in both IL‐12 and type I IFN receptor that develop a T helper type 17‐dominated CD4+ T‐cell response. Despite increased CD4+ T‐cell IL‐17 production, L. monocytogenes‐specific T cells re‐expanded and conferred protection against secondary challenge with virulent L. monocytogenes regardless of IL‐21 deficiency, or combined defects in IL‐21, IL‐12, and type I IFN receptor. Together, these results demonstrate non‐essential individual and combined roles for IL‐21, IL‐12 and type I IFNs in priming pathogen‐specific CD8+ T cells, and reveal IL‐21‐dependent suppression of IL‐17 production by CD4+ T cells during in vivo infection.
Distribution and development of the postnatal murine Vδ1 T‐cell receptor repertoire
Authors: Holtmeier Wolfgang , Gille Jens , Zeuzem Stefan , Šinkora Marek
Published: May 2010

Murine γ/δ T cells express canonical Vγ5Vδ1 chains in the epidermis and Vγ6Vδ1 chains at reproductive sites. Both subsets carry an identical Vδ1‐Dδ2‐Jδ2 chain which completely lacks junctional diversity. These cells are thought to monitor tissue integrity via recognition of stress‐induced self antigens. In this study, we showed by reverse transcription–polymerase chain reaction (RT‐PCR), complementarity determining region 3 (CDR3) spectratyping and sequencing of the junctional regions of Vδ1 chains from C57BL/6 mice (aged 1 day to 14 months) that the canonical Vδ1‐Dδ2‐Jδ2 chain is also consistently present at other sites such as the thymus, gut, lung, liver, spleen and peripheral blood. In addition, we found multiple Vδ1 chains with fetal type rearrangements which were also shared among organs and among animals. These Vδ1 chains were typically characterized by a conserved amino acid motif, ‘GGIRA’. Furthermore, by analysing the early postnatal period at days 10 and 16, we demonstrated that the diversification of the thymic Vδ1 repertoire is not paralleled by a diversification of extrathymic Vδ1+γ/δ T cells. This indicates that only fetal type rearrangements survive at extrathymic sites. In conclusion, γ/δ T cells expressing the canonical Vδ1‐Dδ2‐Jδ2 chain are not unique to the skin and reproductive sites. Furthermore, we found other γ/δ T cells expressing fetal type Vδ1 chains which were shared among different organs and animals. Thus, γ/δ T cells expressing conserved Vδ1 chains are likely to have important functions. We suggest a model in which this subset continuously recirculates throughout the organism and rapidly responds to stress‐induced self antigens.
PCR assays for the sugarcane rust pathogens Puccinia kuehnii and P. melanocephala and detection of a SNP associated with geographical distribution in P. kuehnii
Authors: Glynn N. C. , Dixon L. J. , Castlebury L. A. , Szabo L. J. , Comstock J. C.
Published: May 2010

Puccinia kuehnii and P. melanocephala cause orange and brown rust of sugarcane, respectively. Puccinia kuehnii has been confirmed in Asia, Australia and recently, the Caribbean basin, whereas P. melanocephala is distributed among the majority of sugarcane growing regions. Differentiating these two economically significant pathogens visually is problematic and limited to material exhibiting mature disease symptoms or spores. Partial ITS1, ITS2 and complete 5·8S sequences were generated from P. kuehnii and P. melanocephala isolates from around the world. PCR primers and dual labelled hydrolysis probes were designed for each pathogen for use in real‐time PCR and optimized using locked nucleic acids (LNA). The primers amplified DNA from their target pathogens and not from other species of Puccinia or fungal species isolated from sugarcane leaves. Optimized real‐time PCR conditions allowed the detection of 0·19 pg of P. kuehnii or P. melanocephala genomic DNA and differentiated the pathogens on sugarcane leaves prior to observing typical symptoms in the field. Primer‐introduced restriction analysis‐PCR (PIRA‐PCR) was used to detect a single nucleotide polymorphism (Pk ITS1 183A>G) in ITS1 of P. kuehnii. Allele 183A was observed in all samples, whereas 183G was detected in 52% of samples from Asia and Australia yet absent from all Caribbean basin samples. Long distance spore dispersal, dispersal through an intermediate location or improper movement of contaminated material could explain the introduction of P. kuehnii to the Western hemisphere. However, the current proliferation of the pathogen in the Americas is limited to isolates which contain only the 183A allele.
Molecular and phenotypic features of Pseudomonas syringae pv. actinidiae isolated during recent epidemics of bacterial canker on yellow kiwifruit (Actinidia chinensis) in central Italy
Authors: Ferrante P. , Scortichini M.
Published: May 2010

Pseudomonas syringae pv. actinidiae (Psa) was identified as the causal agent of severe epidemics of bacterial canker on Actinidia chinensis (yellow kiwifruit) in central Italy occurring during 2008–9. A total of 101 strains were obtained from infected leaves, twigs, branches and trunks of cvs Hort16A, Jin Tao and CK3. Outbreaks were also found on A. deliciosa cv. Hayward. A representative set of 21 strains were compared with other Psa strains isolated from previous outbreaks in Japan and Italy as well as with P. s. pv. syringae strains obtained from A. chinensis and with strains of genomospecies 8. Repetitive‐sequence PCR (rep‐PCR) typing using BOX and ERIC primer sets revealed that all Psa strains obtained during 2008–9 showed the same fingerprinting profile. This profile, however, was different from those of strains previously isolated in Japan and Italy. Multilocus sequence typing (MLST) of gapA, gltA, gyrB and rpoD revealed a higher genetic variability among the strains than rep‐PCR, with some of them showing the same sequence pattern although isolated from different areas, cultivars and years. None of the recently obtained strains possessed genes coding for phaseolotoxin or coronatine, and all had an effector protein, namely hopA1, differentiating them from the strains causing past outbreaks in Japan and Italy. All isolates were inhibited in vitro by copper‐based compounds, antibiotics, geraniol, citronellol and by a chitin‐based organic compound. The recent epidemics found in central Italy on yellow kiwifruit appear to have been caused by a different Psa population than those previously recorded in Japan, South Korea and Italy.
Development of a simplified NASBA protocol for detecting viable cells of the citrus pathogen Xanthomonas citri subsp. citri under different treatments
Authors: Scuderi G. , Golmohammadi M. , Cubero J. , López M. M. , Cirvilleri G. , Llop P.
Published: May 2010

Nucleic acid sequence based amplification (NASBA) is a method of amplifying RNA, for the detection of RNA viruses and human pathogenic bacteria. Recently, NASBA has also been employed for the detection of plant diseases caused by viruses and quarantine bacteria. A major citrus pathogen, Xanthomonas citri subsp. citri (Xcc), causal agent of citrus bacterial canker, is being studied in depth due to its economic importance, with recent focus concentrating on its viability and survival under different stress conditions and control treatments. In this work, a NASBA protocol using primers for gumD mRNA has been developed to assess the viability of this pathogen under different bacteriocidal treatments. This method is rapid, specific and sensitive, and is able to detect viable bacterial cells, using a hybridization device which allows the visualization of the results in only 30 min. The usefulness of the method has been confirmed with bacterial suspensions subjected to different heat treatments and to sodium orthophenylphenate.
Differential seedling resistance to the eyespot pathogens, Oculimacula yallundae and Oculimacula acuformis, conferred by Pch2 in wheat and among accessions of Triticum monococcum
Authors: Burt C. , Hollins T. W. , Powell N. , Nicholson P.
Published: May 2010

Eyespot is an economically important stem‐base disease of wheat caused by two fungal species: Oculimacula yallundae and Oculimacula acuformis. This study investigated the efficacy of two sources of resistance, viz. the genes Pch1, introgressed into hexaploid wheat from Aegilops ventricosa, and Pch2, identified in wheat cv. Cappelle Desprez, against O. yallundae and O. acuformis separately. In a series of seedling bioassays Pch1 was found to be highly effective against both species. Although Pch2 was found to confer resistance against both pathogen species, it was significantly less effective against penetration from O. yallundae than O. acuformis. Furthermore, a quantitative trait locus (QTL) analysis was not able to locate any resistance to O. yallundae on chromosome 7A of Cappelle Desprez. This has important implications for the use of Pch2 in commercial cultivars as it is necessary to have genes that confer resistance to both pathogens for effective eyespot control. In addition, a set of 22 T. monococcum accessions was screened for resistance to both O. yallundae and O. acuformis to identify potentially novel resistances and to assess the accessions for evidence of differential resistance to the eyespot species. Significant differences in resistance to the two pathogens were identified in four of these lines, providing evidence for differential resistance in T. monococcum. This study demonstrates that future screening for novel sources of eyespot resistance should investigate both pathogen species.
Mold‐sensitivity in children with moderate‐severe asthma is associated with HLA‐DR and HLA‐DQ
Authors: Knutsen A. P. , Vijay H. M. , Kumar V. , Kariuki B. , Santiago L. A. , Graff R. , Wofford J. D. , Shah M. R.
Published: May 2010

To cite this article: Knutsen AP, Vijay HM, Kumar V, Kariuki B, Santiago LA, Graff R, Wofford JD, Shah MR. Mold‐sensitivity in children with moderate‐severe asthma is associated with HLA‐DR and HLA‐DQ. Allergy 2010; 65: 1367–1375.

Background:  Several epidemiologic studies in the United States and Europe have linked Alternaria sensitivity to both persistence and severity of asthma. In this study, we examined T cell responses and HLA class II alleles in children with moderate‐severe asthma.

Methods:  Ninety‐six children with moderate‐severe asthma were compared to 90 children with mild asthma. HLA class II genotyping was performed to determine HLA allelic frequencies. Th1/Th2 Alternaria‐specific T cell cytokine responses were determined by the use of Alternaria‐stimulated cultures. HLA class II restriction was examined by inhibition of Alternaria‐stimulated lymphoproliferative responses with blocking anti‐HLA class II monoclonal antibodies.

Results:  Children with moderate‐severe asthma had significantly increased sensitivities to Aspergillus fumigatus; sensitivities to Alternaria were similar in both moderate‐severe and mild asthmatics. The frequency of HLA‐DRB1*13 alleles were increased in mold‐sensitive moderate‐severe asthmatic children. HLA‐DRB1*03 tended to be increased in mold‐sensitive moderate‐severe asthmatics. The frequency of HLA‐DQB1*03 alleles was significantly decreased in mold and Alternaria‐sensitive moderate‐severe asthma. HLA class II blocking monoclonal antibodies demonstrated HLA‐DR restriction. Alternaria‐stimulated IL‐5 and IL‐13 synthesis was significantly increased in moderate‐severe asthmatics. IL‐5 and IL‐13 synthesis was significantly increased in Alternaria‐stimulated lymphocyte cultures of HLA‐DQB1*03‐ asthmatics compared to HLA‐DQB1*03+ asthmatics.

Conclusions:  In children with Alternaria‐sensitive moderate‐severe asthma, there was increased Th2 sensitivity to Alternaria stimulation. This was associated with HLA‐DR restriction and with increased frequency of HLA‐DRB1*13 and HLA‐DRB1*03. There was decreased frequency of HLA‐DQB1*03 in Alternaria‐sensitive moderate‐severe asthma, suggesting HLA‐DQB1*03 may be protective of the development of Alternaria‐sensitive severe asthma.
Specific recommendations for PROs and HRQoL assessment in allergic rhinitis and/or asthma: a GA2LEN taskforce position paper
Authors: Braido F. , Bousquet P. J. , Brzoza Z. , Canonica G. W. , Compalati E. , Fiocchi A. , Fokkens W. , Gerth van Wijk R. , La Grutta S. , Lombardi C. , Maurer M. , Pinto A. M. , Ridolo E. , Senna G. E. , Terreehorst I. , Todo Bom A. , Bousquet J. , Zuberbier T. , Baiardini I.
Published: May 2010

To cite this article:Braido F, Bousquet PJ, Brzoza Z, Canonica GW, Compalati E, Fiocchi A, Fokkens W, Gerth van Wijk R, La Grutta S, Lombardi C, Maurer M, Pinto AM, Ridolo E, Senna GE, Terreehorst I, Todo Bom A, Bousquet J, Zuberbier T, Baiardini I. Specific recommendations for PROs and HRQoL assessment in allergic rhinitis and/or asthma: a GA2LEN taskforce position paper.Allergy2010;65: 959–968.

The GA2LEN taskforce on Patient‐Reported Outcomes (PROs) and Health‐Related Quality of Life (HRQoL) published in 2009 a position paper concerning PROS and HRQoL assessment in clinical trials on allergy. Because of the specificity of this topic in asthma and rhinitis, specific recommendations are needed. The aim of this position paper is to define PROs and their meaning in asthma and rhinitis research, explore the available tools to provide criteria for a proper choice, identify patient‐related factor which could influence PROs assessment, define specific recommendations for assessment, analysis and results spreading, underline the unexplored areas and unmet needs. PROs assessment is gaining increasing importance, and it must be performed with a rigorous methodological procedure and using validated tools. This approach enables to better understand patient‐related factors influencing clinical trials and real‐life management outcomes, identify patients subgroups that can benefit from specific treatment and management plan and tailor treatment to address PROs (not only physician‐defined targets) to improve asthma and rhinitis management.
IgE‐mediated hypersensitivity reactions to methylprednisolone
Authors: Aranda A. , Mayorga C. , Ariza A. , Doña I. , Blanca‐Lopez N. , Canto G. , Blanca M. , Torres M. J.
Published: May 2010

To cite this article:Aranda A, Mayorga C, Ariza A, Doña I, Blanca‐Lopez N, Canto G, Blanca M, Torres MJ. IgE‐mediated hypersensitivity reactions to methylprednisolone.Allergy2010;65: 1376–1380.

Background: Allergic reactions to systemically administered corticosteroids seem to be infrequent considering their extensive use. The aim of the study was to evaluate the IgE response in patients with immediate allergic reactions to methylprednisolone (MP).

Methods: Four subjects who developed immediate reactions after MP administration and ten controls with good tolerance to MP administration were evaluated. Skin prick and intradermal testing were done using MP, hydrocortisone (HC), and dexamethasone (DX). If negative, a drug provocation test (DPT) was done to confirm the diagnosis and assess cross‐reactivity. Thein vitroIgE response was evaluated by the basophil activation test (BAT) and ImmunoCAP.

Results: Three patients were diagnosed by the presence of a positive skin test in the immediate reading with MP, two by prick and one by intradermal testing, and one patient was skin test negative and diagnosed by DPT. All four patients had good tolerance to HC and DX. The BAT was positive for just MP in those patients with positive skin tests, with all patients being negative for HC and DX. Two patients were also ImmunoCAP positive to MP.

Conclusions: This study confirms the existence of immediate allergic reactions to MP and that some are mediated by specific IgE antibodies. Skin testing, ImmunoCAP and the BAT are useful to confirm the diagnosis.
Micrometer‐sized thread‐like and/or spherical particles in the first fraction of cerebrospinal fluid in patients with bipolar disorder
Authors: Båve Ullvi , Nybom Rolf , Landén Mikael , Wetterberg Lennart
Published: May 2010

Båve U, Nybom R, Landén M, Wetterberg L. Micrometer‐sized thread‐like and/or spherical particles in the first fraction of cerebrospinal fluid in patients with bipolar disorder. Bipolar Disord 2010: 12: 298–305. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S.

Objectives:  Scanning electron microscopy (SEM) is a powerful tool to identify pathogenic factors for which sensitive tests are lacking. The technique has been used to recognize structures in the cerebrospinal fluid (CSF) of patients with schizophrenia. The aim of this study was to use SEM to screen for potential particles in CSF in bipolar disorder.

Methods:  Fresh CSF samples from 56 euthymic bipolar patients, 31 bipolar I disorder and 25 bipolar II disorder, were compared to CSF samples from 20 controls. SEM of two portions of 200 μL filtered CSF was performed; the first 0.6 mL of CSF and the following 12 mL. The microscopic structures were identified and the quantity and patterns were rated by two independent researchers.

Results:  Quantitative SEM examinations showed that of the 56 patients, 11 were free of any SEM structures in CSF, while 45 patients displayed morphological structures in the first 0.6 mL of CSF. By contrast, only 2 patients showed structures in the second CSF fraction drawn from the following mixed 12 mL of CSF. In total, 45 of the 56 patients had either thread‐like, spherical, or both structures in the CSF, compared to none of the 20 controls.

Conclusions:  The identified particles in the first fraction of CSF have previously not been described in patients with bipolar disorder. Hypothetically, the amount of SEM structures in CSF, from none to many, might correlate to the degree of the alleged underlying disease processes in the central nervous system in patients with bipolar disease.
Factors associated with functional recovery in bipolar disorder patients
Authors: Wingo Aliza P , Baldessarini Ross J , Holtzheimer Paul E , Harvey Philip D
Published: May 2010

Wingo AP, Baldessarini RJ, Holtzheimer PE, Harvey PD. Factors associated with functional recovery in bipolar disorder patients. Bipolar Disord 2010: 12: 319–326. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S.

Objectives:  Among bipolar disorder (BPD) patients, functional recovery, defined as regaining individual premorbid residential and vocational status, is far less common than symptomatic recovery. As several factors have tentatively been implicated in outcomes in BPD, we investigated predictors of functional recovery among BPD patients, including demographic, clinical, and neurocognitive factors.

Methods:  We assessed functional recovery status with standardized residential and occupational indices, assessed neurocognitive functioning with performance‐based neuropsychological tests, and collected demographic and clinical information for 65 euthymic or residually depressed Structured Clinical Interview for DSM‐IV‐defined type I or II BPD patients. We examined predictors of functional recovery with multiple logistic regression modeling.

Results:  More education (p = 0.006), fewer years of illness (p = 0.037), and being married (p = 0.045) were associated independently with functional recovery, even after controlling for residual depressive symptoms, diagnostic type (I versus II), and psychiatric comorbidity. Functionally unrecovered BPD patients performed less well than recovered patients on verbal fluency (effect size = 0.54, p = 0.03), a measure of executive functioning, but this difference was not significant when adjusted for residual mood symptoms and education.

Conclusions:  Among euthymic or mildly depressed BPD patients, functional recovery was associated with more education, being married, and fewer years of illness.
Identification of bipolar disorder in women with postpartum depression
Authors: Sharma Verinder , Khan Mustaq
Published: May 2010

Sharma V, Khan M. Identification of bipolar disorder in women with postpartum depression. Bipolar Disord 2010: 12: 335–340. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S.

Objective:  No studies to date have assessed the pharmacological management of treatment‐resistant postpartum depression. We reviewed the pharmacological treatment of postpartum depression in patients diagnosed with treatment‐resistant ‘unipolar’ depression.

Methods:  We conducted a chart review of patients treated consecutively at a perinatal clinic. Treatment‐resistant postpartum depression was defined as a failure to respond to at least one adequate antidepressant trial. Patients were diagnosed using the DSM‐IV criteria, and the Clinical Global Impression–Improvement (CGI‐I) rating scale was used to assess response to various pharmacological interventions.

Results:  The majority of patients (57%, 34/60) referred for postpartum depression actually suffered from bipolar disorder. All patients were on antidepressants at the time of referral, but by the end of the study 37% (22/60) continued on antidepressants alone or in combination with other medications. CGI‐I ratings showed appreciable improvement in depression at the end of six months following the initial consultation. Very much improvement was noted in 65% (39/60) of patients, and 22% (13/60) were considered much improved. The most common change in medication was a switch to or addition of an atypical neuroleptic.

Limitations:  Retrospective design, small sample size, and lack of a control group.

Conclusions:  Management of treatment resistance in women with postpartum depression should be considered within the context of types of mood disorders. Atypical neuroleptics and mood stabilizers used alone or as adjuncts should be considered in the treatment of resistant postpartum depression in patients with a bipolar diathesis.
A prospective latent analyses study of psychiatric comorbidity of DSM‐IV bipolar I and II disorders
Authors: Mantere Outi , Isometsä Erkki , Ketokivi Mikko , Kiviruusu Olli , Suominen Kirsi , Valtonen Hanna M , Arvilommi Petri , Leppämäki Sami
Published: May 2010

Mantere O, Isometsä E, Ketokivi M, Kiviruusu O, Suominen K, Valtonen HM, Arvilommi P, Leppämäki S. A prospective latent analyses study of psychiatric comorbidity of DSM‐IV bipolar I and II disorders. Bipolar Disord 2010: 12: 271–284. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S.

Objective:  To test two hypotheses of psychiatric comorbidity in bipolar disorder (BD): (i) comorbid disorders are independent of BD course, or (ii) comorbid disorders associate with mood.

Methods:  In the Jorvi Bipolar Study (JoBS), 191 secondary‐care outpatients and inpatients with DSM‐IV bipolar I disorder (BD‐I) or bipolar II disorder (BD‐II) were evaluated with the Structured Clinical Interview for DSM‐IV Disorders, with psychotic screen, plus symptom scales, at intake and at 6 and 18 months. Three evaluations of comorbidity were available for 144 subjects (65 BD‐I, 79 BD‐II; 76.6% of 188 living patients). Structural equation modeling (SEM) was used to examine correlations between mood symptoms and comorbidity. A latent change model (LCM) was used to examine intraindividual changes across time in depressive and anxiety symptoms. Current mood was modeled in terms of current illness phase, Beck Depression Inventory (BDI), Young Mania Rating Scale, and Hamilton Depression Rating Scale; comorbidity in terms of categorical DSM‐IV anxiety disorder diagnosis, Beck Anxiety Inventory (BAI) score, and DSM‐IV‐based scales of substance use and eating disorders.

Results:  In the SEM, depression and anxiety exhibited strong cross‐sectional and autoregressive correlation; high levels of depression were associated with high concurrent anxiety, both persisting over time. Substance use disorders covaried with manic symptoms (r = 0.16–0.20, p < 0.05), and eating disorders with depressive symptoms (r = 0.15–0.32, p < 0.05). In the LCM, longitudinal intraindividual improvements in BDI were associated with similar BAI improvement (r = 0.42, p < 0.001).

Conclusions:  Depression and anxiety covary strongly cross‐sectionally and longitudinally in BD. Substance use disorders are moderately associated with manic symptoms, and eating disorders with depressive mood.
Antithetical asymmetry in schizophrenia and bipolar affective disorder: a line bisection study
Authors: Rao Naren P , Arasappa Rashmi , Reddy Nalini N , Venkatasubramanian Ganesan , Gangadhar Bangalore N
Published: May 2010

Rao NP, Arasappa R, Reddy NN, Venkatasubramanian G, Gangadhar BN. Antithetical asymmetry in schizophrenia and bipolar affective disorder: a line bisection study. Bipolar Disord 2010: 12: 221–229. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S.

Objective:  Evolutionary theories link the pathogenesis of psychosis with anomalous brain asymmetry. Research shows that aberrant lateralization is linked to schizophrenia with elevated rates of left‐handedness and reversal of normal cerebral asymmetries. However, lateralization is underexamined in bipolar affective disorder (BPAD) and the available literature suggests the possibility of greater lateralization, which is diametrically opposite to what is observed in schizophrenia. For the first time, we report concurrent analyses of asymmetry in BPAD and schizophrenia using a line bisection task.

Methods:  We examined 164 subjects (31 patients with BPAD in remission, 30 patients with schizophrenia, and 103 healthy controls) using a two‐hand line bisection task with established methodology. Raters with good inter‐rater reliability (intraclass correlation coefficient > 0.8) measured deviation from the center. Task performance was compared using analysis of covariance with age, sex, and education as covariates.

Results:  Study groups did not differ significantly on age, sex, and handedness (p > 0.06). Patients (both schizophrenia and BPAD) had significantly more errors in identifying the center than controls (p < 0.001). Patients with schizophrenia bisected fewer lines at center than controls and BPAD subjects (p < 0.001). Using their right hand, schizophrenia patients had significant rightward deviation and BPAD patients had leftward deviation (p = 0.001). A significant interaction between diagnosis and direction of deviation (p = 0.01) was noted, with significant rightward deviation in schizophrenia and a trend toward leftward deviation in BPAD.

Conclusions:  Study findings suggest attenuation of normal pseudoneglect in schizophrenia and accentuation of normal pseudoneglect in BPAD, indicating lesser lateralization in schizophrenia and possibly greater lateralization in BPAD. From an evolutionary perspective, schizophrenia and BPAD might have antithetical origins.
Pretreatment and outcome correlates of past sexual and physical trauma in 118 bipolar I disorder patients with a first episode of psychotic mania
Authors: Conus Philippe , Cotton Sue , Schimmelmann Benno G , Berk Michael , Daglas Rothanthi , McGorry Patrick D , Lambert Martin
Published: May 2010

Conus P, Cotton S, Schimmelmann BG, Berk M, Daglas R, McGorry PD, Lambert M. Pretreatment and outcome correlates of past sexual and physical trauma in 118 bipolar I disorder patients with a first episode of psychotic mania. Bipolar Disord 2010: 12: 244–252. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S.

Objectives:  To assess the prevalence and correlates of childhood and adolescent sexual and/or physical abuse (SPA) in bipolar I disorder (BDI) patients treated for a first episode of psychotic mania.

Methods:  The Early Psychosis Prevention and Intervention Centre admitted 786 first‐episode psychosis patients between 1998 and 2000. Data were collected from patients’ files using a standardized questionnaire. A total of 704 files were available; 43 were excluded because of a nonpsychotic diagnosis at endpoint and 3 due to missing data regarding past stressful events. Among 658 patients with available data, 118 received a final diagnosis of BDI and were entered in this study.

Results:  A total of 80% of patients had been exposed to stressful life events during childhood and adolescence and 24.9% to SPA; in particular, 29.8% of female patients had been exposed to sexual abuse. Patients who were exposed to SPA had poorer premorbid functioning, higher rates of forensic history, were less likely to live with family during treatment period, and were more likely to disengage from treatment.

Conclusions:  SPA is highly prevalent in BDI patients presenting with a first episode of psychotic mania; exposed patients have lower premorbid functional levels and poorer engagement with treatment. The context in which such traumas occur must be explored in order to determine whether early intervention strategies may contribute to diminish their prevalence. Specific psychological interventions must also be developed.
Association between mood stabilizers and hypothyroidism in patients with bipolar disorders: a nested, matched case‐control study
Authors: Gau Churn‐Shiouh , Chang Ching‐Jui , Tsai Fang‐Ju , Chao Pei‐Fong , Gau Susan Shur‐Fen
Published: May 2010

Gau C‐S, Chang C‐J, Tsai F‐J, Chao P‐F, Gau SS‐F. Association between mood stabilizers and hypothyroidism in patients with bipolar disorders: a nested, matched case‐control study. Bipolar Disord 2010: 12: 253–263. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S.

Objectives:  This study investigated whether lithium, carbamazepine, and valproate increased the risk for hypothyroidism using Taiwan’s National Health Insurance Dataset.

Methods:  The sample included 557 bipolar disorder patients with incident hypothyroidism first diagnosed between 1998 and 2004, and 2,228 sex‐, age‐, and index date‐matched bipolar disorder patients without hypothyroidism from 1996–2004. We compared the use of lithium, carbamazepine, and valproate before the onset of hypothyroidism between the two groups using a conditional logistical regression model.

Results:  Compared with patients who had never used any of the three mood stabilizers, patients were more likely to have hypothyroidism if they only used carbamazepine [odds ratio (OR) = 1.68; 95% confidence interval (CI): 1.07–2.65]; or comedication of lithium and valproate (OR = 2.40; 95% CI: 1.70–3.40), lithium and carbamazepine (OR = 1.52; 95% CI: 1.10–2.08), and three mood stabilizers (OR = 2.34; 95% CI: 1.68–3.25). There was a dose‐response relationship between the number of mood stabilizers and risk for hypothyroidism (OR = 1.34, 95% CI: 1.21–1.49) and a significant interaction between lithium and valproate on the risk for hypothyroidism (p = 0.020).

Conclusions:  Our findings indicate that lithium, carbamazepine, and valproate may increase the risk for hypothyroidism, particularly if combined, and suggest regular monitoring of thyroid function and monotherapy of mood stabilizers for treating patients with bipolar disorders.