bluuebunny/crossref_metadata_2025 huggingface dataset:
Complement membrane attack is required for endplate damage and clinical disease in passive experimental myasthenia gravis in Lewis rats
Authors: Chamberlain-Banoub J , Neal J W , Mizuno M , Harris C L , Morgan B P
Published: August 2006

Myasthenia gravis (MG) is a debilitating and potentially fatal neuromuscular disease characterized by the generation of autoantibodies reactive with nicotinic acetylcholine receptors (AChR) that cause loss of AChR from the neuromuscular endplate with resultant failure of neuromuscular transmission. A role for complement (C) in the pathology of human MG has been suggested based upon identification of C activation products in plasma and deposited at the endplate in MG. In the rat model, experimental autoimmune MG (EAMG), C depletion or inhibition restricts clinical disease, further implicating C in pathology. The mechanisms by which C activation drives pathology in MG and EAMG are unclear. Here we provide further evidence implicating C and specifically the membrane attack complex (MAC) in the Lewis rat passive EAMG model of MG. Rats deficient in C6, an essential component of the MAC, were resistant to disease induction and endplate destruction was reduced markedly compared to C6-sufficient controls. After reconstitution with C6, disease severity and endplate destruction in the C6-deficient rats was equivalent to that in controls. The data confirm the essential role of the MAC in the destruction of the endplate in EAMG and raise the prospect of specific MAC inhibition as an alternative therapy in MG patients resistant to conventional treatments.
Hypoxia induces expression of connective tissue growth factor in scleroderma skin fibroblasts
Authors: Hong K-H , Yoo S-A , Kang S-S , Choi J-J , Kim W-U , Cho C-S
Published: August 2006

Connective tissue growth factor (CTGF) plays a role in the fibrotic process of systemic sclerosis (SSc). Because hypoxia is associated with fibrosis in several profibrogenic conditions, we investigated whether CTGF expression in SSc fibroblasts is regulated by hypoxia. Dermal fibroblasts from patients with SSc and healthy controls were cultured in the presence of hypoxia or cobalt chloride (CoCl2), a chemical inducer of hypoxia-inducible factor (HIF)-1α. Expression of CTGF was evaluated by Northern and Western blot analyses. Dermal fibroblasts exposed to hypoxia (1% O2) or CoCl2 (1–100 µM) enhanced expression of CTGF mRNA. Skin fibroblasts transfected with HIF-1α showed the increased levels of CTGF protein and mRNA, as well as nuclear staining of HIF-1α, which was enhanced further by treatment of CoCl2. Simultaneous treatment of CoCl2 and transforming growth factor (TGF)-β additively increased CTGF mRNA in dermal fibroblasts. Interferon-γ inhibited the TGF-β-induced CTGF mRNA expression dose-dependently in dermal fibroblasts, but they failed to hamper the CoCl2-induced CTGF mRNA expression. In addition, CoCl2 treatment increased nuclear factor (NF)-κB binding activity for CTGF mRNA, while decreasing IκBα expression in dermal fibroblasts. Our data suggest that hypoxia, caused possibly by microvascular alterations, up-regulates CTGF expression through the activation of HIF-1α in dermal fibroblasts of SSc patients, and thereby contributes to the progression of skin fibrosis.
The testes‐specific bZip type transcription factor Tisp40 plays a role in ER stress responses and chromatin packaging during spermiogenesis
Authors: Nagamori Ippei , Yomogida Kentaro , Ikawa Masahito , Okabe Masaru , Yabuta Norikazu , Nojima Hiroshi
Published: August 2006

We previously reported that the spermatid‐specific transcription factor Tisp40 functions through UPRE and CRE. To investigate Tisp40 function in vivo, we generated TISP40(–/–) mice. TISP40(–/–) mice were born at expected ratios, were healthy, and mutant males bred normally. However, the ER stress‐response protein Grp78/BiP accumulated in the TISP40(–/–) testis and RAMP4 (Ribosome‐associated membrane protein 4) mRNA level was up‐regulated. Disruption of TISP40 caused ER stress and activation of caspase 12 but not caspase 9, leading to apoptosis of meiotic/postmeiotic germ cells. On the other hand, DAPI staining and electron microscopy revealed that epididymal sperm nuclei were abnormally relaxed in the TISP40(–/–) testis, a phenotype that was independent of the expression and maturation of transition proteins and protamines but due to abnormally retained histones. Histones localized to the cytoplasm as well as to the nucleus and were also retained in epididymal sperm. Histones H2A and H4 were dramatically up‐regulated and the acetylation of H2A, H2B and H4 was also enhanced in the TISP40(–/–) testis. Taken together, we conclude that Tisp40 plays an important role in the unfolded protein response of the testis and in regulating the maturation of sperm head nuclei.
Ammonium transporter genes in the fission yeast Schizosaccharomyces pombe: role in ammonium uptake and a morphological transition
Authors: Mitsuzawa Hiroshi
Published: August 2006

Ammonium is an important source of nitrogen for many microorganisms, including yeast, and its availability also has substantial effects on the nitrogen metabolism and development of yeast cells. Three ammonium transporter genes of the fission yeast Schizosaccharomyces pombe, named amt1, amt2, and amt3, were identified on the basis of amino acid sequence similarity to members of the ammonium transporter/methylammonium permease (Amt/Mep) family. A series of strains were constructed that carry all combinations of amt deletion (amtΔ) mutations, and tested for growth on low ammonium and resistance to the toxic ammonium analog methylammonium. The amt1Δ and amt2Δ single mutants had different growth defects, and the amt1Δamt2Δ double mutant displayed a much more severe growth defect on ≤ 5 mm ammonium. All single mutants exhibited methylammonium resistance but to different extents: amt2Δ was the most resistant and amt3Δ was the least. These results suggest that the amt genes encode functional transporters with distinct uptake properties. In response to ammonium limitation, the wild‐type strain isogenic to the amtΔ mutants underwent filamentous growth underneath the surface of solid medium. No such filamentous invasive growth, however, was observed for the amt1Δ mutant, indicating that Amt1 transporter is required for ammonium limitation‐induced filamentous invasive growth.
New reporter system for Per1 and Bmal1 expressions revealed self‐sustained circadian rhythms in peripheral tissues
Authors: Nishide Shin‐ya , Honma Sato , Nakajima Yoshihiro , Ikeda Masaaki , Baba Kenkichi , Ohmiya Yoshihiro , Honma Ken‐ichi
Published: August 2006

A new reporter system for monitoring expressions of two clock genes, Per1 and Bmal1, from a single tissue in culture was developed in mice. Reporters are Vargula hilgendorfii luciferase (VL) and firefly luciferase (FL), whose activities are increased in parallel with Per1 and Bmal1 expressions, respectively. Formal properties of the circadian system in transgenic mice are indistinguishable from those in wild‐type animals. Circadian rhythms in Per1‐VL and Bmal1‐FL in the suprachiasmatic nucleus (SCN) were robust and anti‐phasic, although they were phase delayed by 4–8 h as compared with circadian rhythms in respective transcript levels in vivo. In peripheral tissues such as liver, circadian rhythms in Bmal1‐FL persisted for more than 3 weeks. In the course of prolonged culture, circadian rhythms apparently damped out, but were restored immediately by refreshment of the culture medium. Restoration of the circadian rhythm is unlikely to be due to resetting of desynchronized population oscillation, because peripheral circadian rhythms did not show a type 0 phase response curve (PRC) for medium refreshment, a requirement for instantaneous resetting of circadian oscillation. Long‐term persistence of circadian oscillation in spite of external perturbations supports an idea that circadian oscillations in peripheral tissues are self‐sustained.
Effect of water washing on the functional and rheological properties of proteins from threadfin bream (Nemipterus japonicus) meat
Authors: Karthikeyan M. , Dileep A.O. , Shamasundar B.A.
Published: August 2006

The effect of the number of water washing cycles on the proximate composition, physicochemical and functional properties of proteins from threadfin bream meat was studied. Contents of proteins, fat, ash and non‐protein nitrogen showed a significant (P < 0.05) decrease with the number of washing cycles. The removal of low molecular weight components and increase in the concentration of high molecular weight components was confirmed by gel filtration profile and sodium dodecyl sulphate polyacrylamide gel electrophoresis. The water absorption, fat absorption and emulsion capacity parameters showed a positive correlation with the number of washing cycles. The gel‐forming ability showed a marked improvement with the number of washing cycles. The dynamic viscoelastic behaviour of unwashed and washed meat showed a structure build‐up reaction and was more pronounced in once washed meat. The flow behaviour of total protein solution from unwashed and washed meat showed a pseudoplastic behaviour.
PBP3 inhibition elicits adaptive responses in Pseudomonas aeruginosa
Authors: Blázquez Jesús , Gómez‐Gómez José‐María , Oliver Antonio , Juan Carlos , Kapur Vivek , Martín Soledad
Published: August 2006

Adaptive evolution depends on both the genetic variability in a population of organisms and the selection of the better adapted genotypes. However, for the fittest variants to be selected they must survive over a sufficient period under the new conditions. Bacteria are often exposed to different types of stress in nature, including antibiotics. We analysed the global expression profiles of the opportunistic pathogen Pseudomonas aeruginosa in response to ceftazidime, a PBP3 inhibitor, at different concentrations and times. PBP3 inhibition exerts a global impact on the transcription of a large number of genes. From an adaptive perspective, it is noteworthy the induction of several SOS genes, as well as adaptation, protection and antibiotic resistance genes. Intriguingly, transcription of pyocin genes, previously described as SOS‐regulated, was repressed upon PBP3 inhibition. Ciprofloxacin, an SOS inducer, produced transcriptional induction of pyocins. Our results indicate that: (i) the SOS responses resulting from treatments with these two antibiotics cause only partially overlapping transcription profiles; (ii) PBP3 and DNA‐gyrase inhibition produce opposite effects on transcription of pyocin genes. Consequently, ceftazidime decreases ciprofloxacin toxicity; (iii) error‐prone DNA‐polymerase DinB is induced by PBP3 inhibition but not by DNA‐gyrase inhibition; (iv) PBP3 inhibition causes induced mutagenesis; (v) ceftazidime upregulates several antibiotic‐resistance and adaptation genes; and (vi) ceftazidime concentrations thought previously to be lethal are not, as most cells treated with ceftazidime remain alive and recover their capacity to form colonies. Thus, transcriptional changes demonstrated in this work are likely to be adaptively relevant to cells that survive.
PfCRT and the trans‐vacuolar proton electrochemical gradient: regulating the access of chloroquine to ferriprotoporphyrin IX
Authors: Bray Patrick G. , Mungthin Mathirut , Hastings Ian M. , Biagini Giancarlo A. , Saidu Dauda K. , Lakshmanan Viswanathan , Johnson David J. , Hughes Ruth H. , Stocks Paul A. , O'Neill Paul M. , Fidock David A. , Warhurst David C. , Ward Stephen A.
Published: August 2006

It is accepted that resistance of Plasmodium falciparum to chloroquine (CQ) is caused primarily by mutations in the pfcrt gene. However, a consensus has not yet been reached on the mechanism by which resistance is achieved. CQ‐resistant (CQR) parasite lines accumulate less CQ than do CQ‐sensitive (CQS) parasites. The CQR phenotype is complex with a component of reduced energy‐dependent CQ uptake and an additional component that resembles energy‐dependent CQ efflux. Here we show that the required energy input is in the form of the proton electrochemical gradient across the digestive vacuole (DV) membrane. Collapsing the DV proton gradient (or starving the parasites of glucose) results in similar levels of CQ accumulation in CQS and CQR lines. Under these conditions the accumulation of CQ is stimulated in CQR parasite lines but is reduced in CQS lines. Energy deprivation has no effect on the rate of CQ efflux from CQR lines implying that mutant PfCRT does not function as an efflux pump or active carrier. Using pfcrt‐modified parasite lines we show that the entire CQ susceptibility phenotype is switched by the single K76T amino acid change in PfCRT. The efflux of CQ in CQR lines is not directly coupled to the energy supply, consistent with a model in which mutant PfCRT functions as a gated channel or pore, allowing charged CQ species to leak out of the DV.
Deletion of the gliP gene of Aspergillus fumigatus results in loss of gliotoxin production but has no effect on virulence of the fungus in a low‐dose mouse infection model
Authors: Kupfahl Claudio , Heinekamp Thorsten , Geginat Gernot , Ruppert Thomas , Härtl Albert , Hof Herbert , Brakhage Axel A.
Published: August 2006

Gliotoxin is a secondary metabolite produced by several fungi including the opportunistic human pathogen Aspergillus fumigatus. As gliotoxin exerts immunosuppressive effects in vitro and in vivo, a role as a virulence determinant in invasive aspergillosis has been discussed for a long time but evidence has not been provided until now. Here, by the use of different selection marker genes A. fumigatus knock‐out strains were generated that are deficient for the non‐ribosomal peptide synthetase GliP, the putative key enzyme of the gliotoxin biosynthesis. Deletion of the gliP gene resulted in loss of gliotoxin production, as analysed by high performance liquid chromatography and tandem mass spectrometry. No differences in morphology or growth kinetics between wild‐type and gliP‐deletion strains were observed. In vitro, the culture supernatant of the gliP‐deficient strains showed a reduced cytotoxic effect on both macrophage‐like cells and T cell lines. In a low‐dose murine infection model of invasive aspergillosis, gliotoxin was detected in the lung and absent when mice were infected with the gliP deletion strain. However, gliP deletion strains showed no difference in virulence compared with the corresponding wild‐type strains. Taken together, the non‐ribosomal peptide synthetase GliP is essential for gliotoxin production in A. fumigatus. Gliotoxin is not required for pathogenicity of the fungus in immunocompromised mice, despite the fact that a reduced cytotoxicity of the culture supernatant of gliP deletion strains was demonstrated.
Cutaneous squamous cell carcinoma of the lower limbs in Goiânia, Goiás, Brazil
Authors: Quinteiro Ribeiro Ana Maria , Curado Maria Paula , Benevides Santana Filho Jales
Published: August 2006

Background Cutaneous squamous cell carcinoma is a common malignant neoplasm that affects areas that are exposed to the sun in fair‐skinned people. It occurs less frequently on the lower limbs where other etiological factors are involved.

Objective To determine the epidemiological aspects of cutaneous squamous cell carcinoma of the lower limbs in Goiânia.

Methodology Forty‐three cases of cutaneous squamous cell carcinoma of the lower limbs from the Cancer Registry of the Population Base of Goiás, for the period between 1995 and 1999, were included in the study.

Results Among the cases of cutaneous squamous cell carcinoma registered in this 5‐year interval, 43 (4.6%) represented cases affecting the lower limbs. Of these individuals, seven (16.3%) were male and 36 (83.7%) female (P < 0.001). Those in the age group of 60 years and above represented 90.7% of the cases (P < 0.001). None of the patients had metastasis.

Conclusion Cutaneous squamous cell carcinomas on the lower limbs are more frequently seen in women older than 60 years of age, and they rarely metastasize.
Microscopic study of normal skin in cases of mycosis fungoides
Authors: El‐Darouti Mohammad A. , Marzouk Salonaz A. , Bosseila Manal , Zeid Ola Abu , El‐Safouri Omar , Zayed Amira , El‐Ramly Amany , Abdel‐Halim Mona R. E.
Published: August 2006

Background  During therapy of patients with mycosis fungoides (MF) at the Department of Dermatology, Kasr El‐Aini Hospital, follow‐up biopsies are routinely taken every 2 months. It was noticed that lesions of MF might become clinically normal during treatment, and yet still show microscopical evidence of MF. This finding raised the possibility that clinically normal skin in MF could be microscopically involved.

Aim  The aim of our work was to evaluate the degree of histopathological involvement of normal‐looking skin in patients with MF.

Patients and methods  Thirty patients with stage IB were biopsied from their normal skin. Two biopsies were taken: one proximal (2 cm) and the other distal (> 5 cm) from any visible lesion. Ten normal controls were included in the study. All specimens were stained with H&E and examined microscopically. The microscopical diagnosis was confirmed by immunophenotyping.

Results  Epidermotropism was detected in 21 (70%) of the proximal skin biopsies and 14 (47%) of the distal skin biopsies, whereas no biopsy from the control group showed epidermotropism. All the proximal skin biopsies showed dermal infiltrate and 90% of the biopsies from the distal normal skin showed dermal infiltrate (mostly superficial perivascular).

Conclusion  Normal skin in patients with MF could be affected microscopically and this may raise questions regarding the credibility of the current staging classification of MF, and may necessitate taking biopsies from normal skin before starting topical treatment. During MF treatment, biopsies from cured lesions are required before starting withdrawal.
Autoimmune subepidermal blistering diseases in Uganda: correlation of autoantibody class with age of patients
Authors: Mulyowa Grace K. , Jaeger Gerold , Kabakyenga Jerome , Bröcker Eva‐B. , Zillikens Detlef , Schmidt Enno
Published: August 2006

Background  No data are available on the incidence and immunoreactivity of autoimmune subepidermal blistering skin diseases in East Africa.

Methods  All patients with frank blisters/erosions on the skin and/or mucous membranes that attended the Department of Dermatology at Mbarara University, Uganda, from May 2000 to June 2002, were investigated. The diagnosis was based on the clinical presentation and on the presence of circulating autoantibodies detected by indirect immunofluorescence microscopy on 1 m NaCl‐split human skin and by Western blotting of recombinant and cell‐derived forms of BP180, BP230, and type VII collagen.

Results  Twenty‐two patients with autoimmune subepidermal blistering skin disorders were identified, including nine with bullous pemphigoid (41%), four with linear immunoglobulin A (IgA) disease (18%), three with mucous membrane pemphigoid (14%), two with linear IgG/IgA bullous dermatosis (9%), and one each with cicatricial pemphigoid and epidermolysis bullosa acquisita (5%). In addition, two patients with immunoreactivity to both the epidermal and dermal side of salt‐split skin by indirect immunofluorescence microscopy, who were unreactive to type VII collagen, were provisionally diagnosed as “mixed pemphigoid” (9%). In patients with subepidermal blistering diseases, IgG reactivity correlated significantly with old age, whereas younger patients preferentially developed IgA autoantibodies (P = 0.024).

Conclusions  The age of patients with autoimmune subepidermal blistering diseases appears to influence the immunoglobulin class of autoantibodies. The high frequency of IgA autoantibodies in Ugandan patients may be explained by the age distribution of the Ugandan population.
Ivermectin treatment of three cases of demodecidosis during human immunodeficiency virus infection
Authors: Clyti Emmanuel , Nacher M. , Sainte‐Marie D. , Pradinaud R. , Couppie P.
Published: August 2006

Demodecidosis is an ectoparasitosis that is infrequently observed in subjects with human immunodeficiency virus (HIV) infection. It has a rosacea‐like presentation. We present three cases in patients with acquired immunodeficiency syndrome (AIDS). Two of these patients had a profuse eruption, and all three cases were cured by ivermectin. The single‐dose treatment could be repeated in cases of subsequent recurrence. Ivermectin thus seems to be a good alternative in the treatment of demodecidosis in patients with HIV infection.
Delayed complications of sulfur mustard poisoning in the skin and the immune system of Iranian veterans 16–20 years after exposure
Authors: Hefazi Mehrdad , Maleki Masoud , Mahmoudi Mahmoud , Tabatabaee Abbas , Balali‐Mood Mahdi
Published: August 2006

Background  Extensive cutaneous burns caused by alkylating chemical warfare agent sulfur mustard (SM) have been associated with the severe suppression of the immune system in humans. We aimed to study the association between late cutaneous and immunological complications of SM poisoning.

Methods  Skin examination was performed on all SM‐poisoned Iranian veterans in the province of Khorasan, Iran, who had significant clinical complications, and their SM intoxication was confirmed by toxicological analysis. Light microscopy was performed on eight skin biopsies. Blood cell counts, serum immunoglobulin and complement factor, as well as flow cytometric, analyses were performed on all the patients. The severity of cutaneous complications were classified into four grades and compared with hematological and immunological parameters, using Spearman's rank correlation test.

Results  Forty male subjects, confirmed with SM poisoning 16–20 years earlier, were studied. The main objective findings were hyperpigmentation (55%), dry skin (40%), multiple cherry angiomas (37.5%), atrophy (27.5%), and hypopigmentation (25%). Histopathologic findings were nonspecific and compatible with hyperpigmented old atrophic scars. Except for the hematocrit and C4 levels, hematological and immunological parameters revealed no significant correlation with the severity grades of cutaneous complications.

Conclusion  Sulfur mustard is an alkylating agent with prolonged adverse effects on both the skin and the immune system. Allthough skin is a major transporting system for SM's systemic absorption, there is probably no correlation between the severity of late cutaneous and immunological complications of SM poisoning.
Onychoprotothecosis: Report of the first case in Brazil
Authors: Zaitz Clarisse , Miranda Godoy Andrea , De Sousa Valéria Maria , Ruiz Ligia Rangel B. , Masada Andréa S. , Nobre Márcia Valéria , Alencar Santos Ana Regina , Marques Ana Cristina , Hitomi Muramatu Laura , Hernandez Arrigada Giovanna Letícia , Heins‐Vaccari Elisabeth Maria , Costa Martins José Eduardo
Published: August 2006

The present report describes a case of onychoprotothecosis caused by Prototheca wickerhamii in a nonimmunocompromized female. Dermatological examination showed yellowish discoloration of the left and right forefinger nails, showing onicolysis and hyperkeratosis. The repeated isolation of the algae Prototheca (organisms morula‐like) as well as the repeated culture in media, Sabouraud agar, confirmed the diagnosis. The patient was successfully treated with tioconazol 1% topic solution. The aim of this paper was to present a rare condition.
Immunology highlights at high altitude: review of the fourth EAACI‐GA2LEN Davos Meeting
Authors: Gutermuth J. , Köllisch G. , Bewersdorff M. , Braun A. , Alessandrini F. , Jakob T.
Published: August 2006

The field of allergy is moving fast. To keep pace with the underlying immunologic mechanisms, the 4th EAACI‐GA2LEN Davos meeting on ‘Basic Immunology Research in Allergy and Clinical Immunology’ was organized in Grainau, Germany, February 16th–19th, 2006 by the Immunology Section of the European Academy of Allergy and Clinical Immunology and the ZAUM – Center for Allergy and Environment, Technical University Munich, with generous support from GA2LEN. Recent advances and new insights on innate and adaptive immunity, environmental factors influencing immune responses, immune regulation and allergic inflammation were presented by keynote speakers and selected participants.
Clinical efficacy and safety of sublingual immunotherapy with tree pollen extract in children
Authors: Valovirta E. , Jacobsen L. , Ljørring C. , Koivikko A. , Savolainen J.
Published: August 2006

Background:  Subcutaneous immunotherapy has been the principal approach of immunotherapy in the treatment of allergic diseases. Several clinical studies with birch, alder or hazel pollen extract conducted as subcutaneous immunotherapy have been published suggesting a well‐tolerated and clinically effective treatment. Only a few clinical studies of sublingual immunotherapy (SLIT) with these allergens have been published. This study investigated the clinical efficacy, safety and dose–response relationship of SLIT in children suffering from rhinoconjunctivitis with/without asthma.

Methods:  Eighty‐eight children (5–15 years) with a history of tree pollen‐induced allergic rhinoconjunctivitis with/without seasonal asthma for ≥2 years were included. Allergy to tree pollen was confirmed by positive skin‐prick test, positive specific IgE and positive conjunctival provocation test. The extract used was a glycerinated mixture of Betula verrucosa, Corylus avellana and Alnus glutinosa 100 000 SQ‐U/ml. Children were randomized into three groups receiving SLIT 5 days a week for up to 18 months; dose group 1: accumulated weekly dose of 24 000 SQ‐U; dose group 2: accumulated weekly dose of 200 000 SQ‐U; and placebo.

Results:  In the birch pollen season, dose group 2 showed a significant reduction of symptom (P = 0.01) and medication scores (P = 0.04) compared with placebo. Dose group 1 showed a significant reduction of symptom scores (P = 0.03). There were no statistical differences between dose groups 1 and 2. All children tolerated the treatment well.

Conclusion:  SLIT with tree pollen extract provided dose‐dependent benefits in tree pollen‐allergic children in terms of significantly reduced symptoms and medication use. The treatment was well tolerated.
The α‐chain of high‐affinity receptor for IgE (FcɛRIα) gene polymorphisms and serum IgE levels
Authors: Potaczek D. P. , Sanak M. , Mastalerz L. , Setkowicz M. , Kaczor M. , Nizankowska E. , Szczeklik A.
Published: August 2006

Background:  The high‐affinity receptor for immunoglobulin‐E (IgE) (FcɛRI) plays a major role in the pathogenesis of allergy, but there are only two published studies on its α subunit (FcɛRIα) genetic variability in allergic diseases.

Aims of the study:  Mutational screening in the region of the FcɛRIα gene promoter and the first exon with subsequent genetic variability assessment in allergic patients and a random population sample.

Methods:  Allergic subjects were individuals with asthma or urticaria. Age‐ and sex‐matched controls were randomly selected from a large population sample. Mutational screening was performed using a single‐stranded conformational polymorphism and subsequent sequencing. Detected polymorphisms were genotyped by restriction fragment length polymorphism. Total serum IgE was measured in allergic subjects and controls. Skin prick tests, blood eosinophil count and aspirin challenge test were performed only in the subjects. A subgroup of the subjects was further characterized by autologous serum skin test, histamine release test, Phadiatop and IgE antibodies against staphylococcal enterotoxins.

Results:  Two linked polymorphisms −344 C>T and −95 T>C were found within the FcɛRIα gene. The allele −344 T frequency was 0.45 vs 0.37 (P = 0.33), and the allele −95 C frequency was 0.26 in subjects vs 0.30 in controls (P = 0.62). Serum IgE was significantly higher in subjects homozygous for the −344T allele (TT genotype) than in those carrying the −344 C allele (CT or CC genotype; P = 0.003), but this association was not detectable in controls.

Conclusions:  Our findings of genotype‐related differences in IgE levels in allergic patients suggest an impact of −344 C>T but not −95 T>C gene polymorphism of FcɛRIα on total levels of IgE. The genetic variability in FcɛRIα at the −344 nucleotide of its regulatory sequence, though not related to atopy, predicts higher levels of the immunoglobulin.
Sublingual immunotherapy in children modulates allergen‐induced in vitro expression of cytokine mRNA in PBMC
Authors: Savolainen J. , Jacobsen L. , Valovirta E.
Published: August 2006

Background:  During subcutaneous immunotherapy (SCIT), there is a local mucosal shift from Th2 to Th1 type cytokine predominance and downregulation of interleukin (IL)‐5 and eosinophilia. According to recent studies IL‐10‐ and transforming growth factor (TGF)‐β‐induced tolerance is another key phenomenon in SCIT. Few data to date is available on mechanisms and roles of these cytokines in sublingual immunotherapy (SLIT).

Scope:  This study was undertaken to analyse the allergen‐induced in vitro mRNA expression of IL‐4, IL‐5, IL‐10, TGF‐β and interferon (IFN)‐γ during SLIT in peripheral blood mononuclear cells (PBMC) of children with allergic rhinitis (AR).

Methods:  Ten patients with AR undergoing pollen SLIT with a weekly dose of 200 000 SQ‐U, 10 with a weekly dose of 24 000 SQ‐U of glycerinated mixture of Betula verrucosa, Corylus avellana and Alnus glutinosa and 10 with placebo were included in the study. Peripheral blood mononuclear cell samples were collected and stimulated with pollen allergen extract prior to the treatment, after 1 and 2 years of the treatment. The cytokine mRNA expression was assessed using kinetic real time reverse transcription polymerase chain reaction (RT‐PCR; TaqMan®).

Results:  The in vitro allergen‐induced mRNA expression of IL‐5 by PBMC in the placebo group at 1 (P = 0.0065) and 2 (P = 0.013) years of therapy were increased in comparison with the highest dose. The expression of IL‐10 mRNA was increased in the highest dose group (P = 0.0016) and the lower dose group (P = 0.034) at 2 years of therapy when compared with placebo. The change in the expression of allergen‐induced TGF‐β had an inversed correlation with the change of IL‐5 (r = −0.38, P = 0.036) and positive correlation with the change of IL‐10 (r = 0.58, P = 0.0019).

Conclusions:  Sublingual immunotherapy induced a dose‐dependent systemic allergen‐specific immunological response in children with AR. During high‐dose SLIT, there was activation of regulatory cytokine IL‐10 and an inhibitory effect on IL‐5 expression increase that was associated with TGF‐β.
In vitro hymenoptera venom allergy diagnosis: improved by screening for cross‐reactive carbohydrate determinants and reciprocal inhibition
Authors: Jappe U. , Raulf‐Heimsoth M. , Hoffmann M. , Burow G. , Hübsch‐Müller C. , Enk A.
Published: August 2006

Background:  Immunoglobulin (Ig) E‐double positivity for honeybee (HB) and yellow jacket (YJ) venom causes diagnostic difficulties concerning therapeutical strategies. The aim of this study was to clarify the cause and relation of the cross‐reactivity in patients with insect venom allergy.

Methods:  For this purpose, 147 patients with suspected stinging insect allergy and CAP‐FEIA‐double positivity were investigated for specific sIgE to additional cross‐reactive carbohydrate determinant (CCD)‐containing allergens: timothy grass pollen, rape pollen, natural rubber latex (NRL), bromelain, and horseradish peroxidase (HRP). Sera with sIgE to NRL were further investigated with the commercially available recombinant latex allergens. Reciprocal inhibition assays with both venoms and HRP were performed.

Results:  About 36 of 147 (24.5%) patients had sIgE to both venoms only. However, 111 of 147 (75.5%) additionally reacted to CCD‐carrying allergens. 89 of 111 CCD‐reactive sera had NRL‐sIgE. In cases where inhibition experiments were performed, the NRL‐sIgE binding was completely abolished in the presence of HRP. Only nine of 61 sera were positive for at least one recombinant latex allergen; all of them were negative in history and NRL‐skin prick test. In 43 sera containing sIgE to CCD, HRP inhibition revealed unequivocal results: In 28 of 43 (65%) an HRP‐inhibition >70% of sIgE to one venom occurred, pointing out the relevant venom. In three of 43 sIgE proved to be entirely CCD‐specific.

Conclusions:  Our data indicate that in cases of IgE positivity to both insect venoms supplementary screening tests with at least one CCD‐containing allergen should be performed; HRP being a suitable tool for this test. In addition, subsequent reciprocal inhibition is an essential diagnostic method to specify cross‐reacting sIgE results.
Silodosin, a new α1A‐adrenoceptor‐selective antagonist for treating benign prostatic hyperplasia: results of a phase III randomized, placebo‐controlled, double‐blind study in Japanese men
Authors: Kawabe Kazuki , Yoshida Masaki , Homma Yukio ,   for the Silodosin Clinical Study Group
Published: August 2006

This section contains papers from Japan, Austria, the UK, and joint papers from France, Denmark, Switzerland, Australia and the USA. A wide variety of lower urinary tract topics is covered, from BPH to overactive bladder and urodynamic stress incontinence.

OBJECTIVE

To verify the efficacy and safety of the new α1A‐adrenoceptor‐selective antagonist silodosin compared with tamsulosin and placebo in patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH).

PATIENTS AND METHODS

This randomized, double‐blind, placebo‐controlled study was conducted at 88 centres in Japan. Men aged ≥50 years with an International Prostate Symptom Score (IPSS) of ≥8, a quality‐of‐life (QoL) score of ≥3, a maximum urinary flow rate (Qmax) of <15 mL/s, a prostate volume of ≥20 mL and a postvoid residual urine volume of <100 mL were eligible for enrolment. Patients were randomized to receive silodosin 4 mg twice daily, tamsulosin 0.2 mg once daily, or placebo, for 12 weeks. The primary endpoint was the change in IPSS from baseline. Safety was assessed by adverse events, physical examination, vital signs and laboratory tests.

RESULTS

In all, 457 patients were randomized (silodosin 176, tamsulosin 192 and placebo 89). The change in the total IPSS from baseline in the silodosin, tamsulosin and placebo groups was −8.3, −6.8 and −5.3, respectively. There was a significant decrease in the IPSS vs placebo in the silodosin group from 1 week. In the early‐stage comparison, silodosin showed a significant decrease in IPSS vs tamsulosin at 2 weeks. The change in QoL from baseline was −1.7, −1.4 and −1.1 in the silodosin, tamsulosin and placebo groups, respectively; silodosin showed a significant improvement in the QoL score vs placebo. In the subgroup of patients with severe symptoms (IPSS ≥20) silodosin also gave a significantly better improvement than placebo (−12.4 vs −8.7). The incidence rates of adverse events and drug‐related adverse events were, respectively, 88.6%, 82.3% and 71.6% and 69.7%, 47.4% and 36.4%, respectively. The most common adverse event in the silodosin group was abnormal ejaculation, which occurred more often in the silodosin than in the tamsulosin group (22.3% vs 1.6%). However, only five men (2.9%) discontinued treatment for abnormal ejaculation.

CONCLUSION

Silodosin was generally effective in the absence of obtrusive side‐effects. This study suggests that silodosin is clinically useful for treating LUTS associated with BPH.
The strategies and limits of gentlemanly capitalism: the London East India agency houses, provincial commercial interests, and the evolution of British economic policy in South and South East Asia 1800–50
Authors: WEBSTER ANTHONY
Published: August 2006

This article explores the development of the London East India agency houses during the first half of the nineteenth century, and their evolving commercial and political relationships with merchants and manufacturers in the British provinces. It outlines the emergence of pressure groups in Britain concerned with influencing British economic policy in India and the Far East, and their role in shaping policy as the East India Company receded in importance following the Charter Acts of 1813 and 1833. What emerges is a complex picture of collaboration between interest groups in London and the provinces. This challenges and refines aspects of the gentlemanly capitalism thesis of Cain and Hopkins, which emphasizes both the supremacy of London‐based financial and mercantile interests in the formation of British policy towards the empire, and the separateness of City‐based ‘gentlemanly capitalists’ from provincial mercantile and industrial interests.
After the Black Death: labour legislation and attitudes towards labour in late‐medieval western Europe
Authors: COHN SAMUEL
Published: August 2006

The Black Death spurred monarchies and city‐states across much of Western Europe to formulate new wage and price legislation. These legislative acts splintered in a multitude of directions that to date defy any obvious patterns of economic or political rationality. A comparison of labour laws in England, France, Provence, Aragon, Castile, the Low Countries, and the city‐states of Italy shows that these laws did not flow logically from new post‐plague demographics and economics—the realities of the supply and demand for labour. Instead, the new municipal and royal efforts to control labour and artisans’ prices emerged from fears of the greed and supposed new powers of subaltern classes and are better understood in the contexts of anxiety that sprung forth from the Black Death’s new horrors of mass mortality and destruction, resulting in social behaviour such as the flagellant movement and the persecution of Jews, Catalans, and beggars.
Dispelling a Myth? The Fathers of Europe and the Construction of a Euro‐Identity
Authors: Petit Isabelle
Published: August 2006

Abstract:  There is a broad agreement on the fact that today there is a wide gap between the European Union (EU) and the citizens of the Member States. According to a common belief, this gap is the result of a deliberate decision made by the founding fathers and subsequent European officials to keep the integration dynamic distant from the people. Yet, if we look closely at their writings and actions that were initiated by the European Commission at an early stage in the integration process, we can only conclude that there is little evidence to support this common belief. On the contrary, it appears that the founding fathers were eager to inform the public on issues related to the communities and that they did not hesitate to support measures aimed at enhancing knowledge about Europe, its policies, and its institutions. It is essential to question these beliefs in order to improve our understanding of the democratic deficit in the EU and especially of the solutions proposed for remedying it. If we admit that the founding fathers never had the intention of keeping the people in ignorance and that some actions were rapidly taken to bring the EU closer to them then it becomes difficult to claim that a reduction of the democratic deficit will follow when decision‐makers simply imagine and adopt programmes aimed at bridging the gap. The question then becomes why have this socialisation and this ‘rapprochement’ not occurred.
Competing for the Highly Skilled Migrants: Implications for the EU Common Approach on Temporary Economic Migration
Authors: Zaletel Petra
Published: August 2006

Abstract:  Globalisation has increased the mobility of people while rapid development of the knowledge economy places human capital at the centre of economic progress. Both result in competition for highly skilled labour among states, particularly the more‐developed states. The EU has a particular role in this global competition for the highly skilled. It is faced with the ageing of its population. Furthermore, the quest to revitalise the EU's economy by implementing the ambitious Lisbon Strategy requires an additional 700,000 research positions. Lastly, the EU is trying to design a common European policy for economic migration, starting with the Green Paper in 2005. This article aims to contribute to a common policy design in the area of highly skilled temporary migration. It compares the UK and German schemes for highly skilled immigrants (the only two in the EU) with the successful US scheme, still seen as the benchmark for the EU. The findings are twofold. First, there is a set of obligatory characteristics that should be introduced to the schemes to make them more attractive. Second, as the programmes are not the only factors that determine the attractiveness of a respective country, the article argues that an EU common policy for highly skilled migrants would make the EU area more attractive as a whole and therefore increase its competitiveness in the global economy.
Neu–Laxova syndrome: a case report and review of the literature
Authors: Ugras M , Kocak G , Ozcan H
Published: August 2006

Neu–Laxova syndrome (NLS) is a rare autosomal recessive syndrome, characterized by severe intrauterine growth retardation (IUGR), microcephaly, abnormal brain development, oedema and ichthyosis. It was first reported in 1971 by Neu et al. (Pediatrics 47: 610–612) and since then no more than 60 cases have been reported. A newborn girl delivered from a 29‐year‐old healthy mother was admitted to hospital with a thick membrane covering her body and dismorphic appearance. The diagnosis of NLS was made according to characteristic features. The syndrome is known to have a poor prognosis and the baby lived for 9 weeks. This case is one of the longest living cases of NLS and the fourth case reported from Turkey.
Clinical features and risk factors for striae distensae in Korean adolescents
Authors: Cho S , Park ES , Lee DH , Li K , Chung JH
Published: August 2006

Background  Despite the high prevalence of striae distensae, clinical studies are few in number, and their pathophysiology still obscure.

Objectives  To determine the prevalence and clinical characteristics of striae distensae that occur in Korean adolescents, and to correlate their clinical features with family history, other dermatological conditions, and body measurements.

Methods  One hundred and fifty‐seven healthy Korean students, aged 15 to 17, were studied. A questionnaire and physical examination were employed to assess the subjects’ past and family history, and the distribution, clinical features and severity of striae distensae.

Results  Striae distensae were present in 131 subjects (83.4%). Ninety‐four (88.2%) of 109 male and 37 (77.1%) of 48 female subjects were affected. The striae were white in colour in 69.5% and asymptomatic in most of the subjects. They developed at an average age of 13.8 years. Family history was present in 18 subjects (11.5%). Seborrhoea of the face was positively correlated (P < 0.035) with striae distensae, and atopic dermatitis negatively correlated (P < 0.001). In both sexes, the buttock was the most prevalent area of striae development, followed by the lower back and knee in boys and by the thigh and calf in girls. Striae were significantly more common on the thigh of girls and on the knee of boys.

Conclusions  Our results indicate that striae distensae are a common skin condition that occurs early in puberty regardless of gender, and that they have a different anatomical distribution and relationship with body measurements in each gender.
Influence of narrow‐band UVB phototherapy on cutaneous microbiota of children with atopic dermatitis
Authors: Silva SH , Guedes ACM , Gontijo B , Ramos AMC , Carmo LS , Farias LM , Nicoli JR
Published: August 2006

Objective  In the present work, the effect of narrow‐band ultraviolet B (UVB) phototherapy on a cutaneous microbial population was evaluated in patients with atopic dermatitis (AD) and compared with control patients (vitiligo).

Methods  Count, isolation and identification of cutaneous microbiota from anticubital fossa were performed in 10 controls and 10 AD patients, both submitted to similar levels (P > 0.05) of UVB phototherapy (4.3 ± 0.9 and 4.3 ± 0.8 accumulated joules, respectively). Additionally, Staphylococcus aureus isolates were screened for the production of exotoxins.

Results  The total and staphylococcal cutaneous microbial population levels were higher (P < 0.05) in AD patients than in the controls. All these population levels decreased (P < 0.05) for both AD and control patients after UVB phototherapy, which also decreased the SCORAD for AD patients. All patients with AD and 50% of controls were carriers of S. aureus, and harboured the bacteria simultaneously on skin and anterior nares. All of the S. aureus strains recovered from AD patient skin produced toxin and the B type was the most frequently detected (70%), followed by C (20%) and A (10%) toxins. Only 40% of the S. aureus isolates from control patients produced toxin. After UVB treatment, microbial population levels of AD patients were similar (P > 0.05) to the ones found in control patients before phototherapy, and toxin production ability of S. aureus isolates decreased drastically.

Conclusion  The results of the present study show the beneficial effect of UVB phototherapy on AD and suggest that this may be attributable not only to reduction of skin surface bacteria but also to the suppression of superantigen production from S. aureus.
Association of HLA haplotype with alopecia areata in Chinese Hans
Authors: Xiao F‐L , Ye D‐Q , Yang S , Zhou F‐S , Zhou S‐M , Zhu Y‐G , Liang Y‐H , Ren Y‐Q , Zhang X‐J
Published: August 2006

Background   Some studies have shown discrepancies in human leucocyte antigen (HLA) associated with alopecia areata (AA) between different ethnic populations.

Objective  To investigate whether HLA‐I, ‐DQA1 and ‐DQB1 alleles and the HLA haplotype are associated with AA, and the correlation between the HLA haplotype profile, age of onset and severity of AA in Chinese Hans.

Methods  The polymerase chain reaction‐sequence specific primer (PCR‐SSP) method was used to analyse the frequencies of HLA class I, ‐DQA1 and ‐DQB1 alleles in 192 patients with AA and 252 controls in Chinese Hans. The linkage disequilibrium was calculated using the 2 × 2 table.

Results  The 24 two‐locus haplotypes [including A*02‐B*18, A*02‐B*27, A*02‐B*52, A*02‐Cw*0704, A*02‐DQA1*0104, A*02‐DQB1*0604, A*02‐DQB1*0606, B*18‐Cw*0704, B*18‐DQA1*0104, B*18‐DQA1*0302, B*18‐DQB1*0606, B*27‐Cw*0704, B*27‐DQA1*0104, B*27‐DQA1*0302, B*52‐Cw*0704, B*52‐DQA1*0104, B*52‐DQA1*0302, B52‐DQB1*0606, Cw*0704‐DQA1*0104, Cw*0704‐DQA1*0302, Cw*0704‐DQB1*0606, DQA1*0104‐DQB1*0604, DQA1*0104‐DQB1*0606, DQA1*0302‐DQB1*0606 (P < 0.05)] were associated with AA, while eight extended haplotypes (A*02‐B*18‐DQA1*0104, A*02‐B*27‐DQA1*0104, A*02‐B*52‐DQA1*0104, A*02‐B*52‐DQA1*0302, A*02‐B*52‐DQB1*0606, B*52‐Cw*0704‐DQA1*0104, B*52‐Cw*0704‐DQA1*0302, A*02‐B*52‐DQA1*0302‐DQB1*0606) were found to be related to AA in Chinese Hans. Through stratified analysis, we found that the extended haplotype B*52‐Cw*0704‐DQA1*0302 was related to early onset of AA, and no haplotype was only associated with severe AA.

Conclusion   This is the first detailed report to elucidate HLA haplotypes associated with AA and that demonstrates the significant HLA haplotypes in Chinese Hans AA. The haplotype B*52‐Cw*0704‐DQA1*0302 was identified to be related to early onset of AA. Our results provide some information for future research on predisposing genes in HLA regions in Chinese Hans.