bluuebunny/crossref_metadata_2025 huggingface dataset:
Phytosphingosine induced mitochondria‐involved apoptosis
Authors: Nagahara Yukitoshi , Shinomiya Takahisa , Kuroda Sachiko , Kaneko Naoki , Nishio Reiji , Ikekita Masahiko
Published: February 2005

Sphingolipids are putative intracellular signal mediators in cell differentiation, growth inhibition, and apoptosis. Sphingosine, sphinganine, and phytosphingosine are structural analogs of sphingolipids and are classified as long‐chain sphingoid bases. Sphingosine and sphinganine are known to play important roles in apoptosis. In the present study, we examined the phytosphingosine‐induced apoptosis mechanism, focusing on mitochondria in human T‐cell lymphoma Jurkat cells. Phytosphingosine significantly induced chromatin DNA fragmentation, which is a hallmark of apoptosis. Enzymatic activity measurements of caspases revealed that caspase‐3 and caspase‐9 are activated in phytosphingosine‐induced apoptosis, but there is little activation of caspase‐8 suggesting that phytosphingosine influences mitochondrial functions. In agreement with this hypothesis, a decrease in ΔΨm and the release of cytochrome c to the cytosol were observed upon phytosphingosine treatment. Furthermore, overexpression of mitochondria‐localized anti‐apoptotic protein Bcl‐2 prevented phytosphingosine apoptotic stimuli. Western blot assays revealed that phytosphingosine decreases phosphorylated Akt and p70S6k. Dephosphorylation of Akt was partially inhibited by protein phosphatase inhibitor OA and OA attenuated phytosphingosine‐induced apoptosis. Moreover, using a cell‐free system, phytosphingosine directly reduced ΔΨm. These results indicate that phytosphingosine perturbs mitochondria both directly and indirectly to induce apoptosis. (Cancer Sci 2005; 96: 83–92)
Follicular lymphoma subgrouping by fluorescence in situ hybridization analysis
Authors: Sekiguchi Naohiro , Kobayashi Yukio , Yokota Yukiko , Kusumoto Shigeru , Tanimoto Kazuki , Watanabe Takashi , Matsuno Yoshihiro , Tobinai Kensei
Published: February 2005

The frequency of t(14;18) in follicular lymphoma (FL) in Japan has been reported to be low compared to North America and other European countries. Recently, it has also been reported that FL lacks t(14;18), mainly among histological grade 3b, and occasionally has a rearranged Bcl‐6 gene. It is not known whether a difference in histology or immunostaining pattern exists between FL with and without t(14;18). We performed interphase fluorescence in situ hybridization (FISH) analysis to detect Bcl‐2/IgH, Bcl‐6 gene rearrangement, Bcl‐2 gene amplification, and the cyclinD1/IgH gene in formalin‐fixed paraffin embedded specimens from our FL archives. The correlation between morphological features, histological grades, immunohistochemical findings, and cytogenetical aberrations was studied. In total, we found that 28 of 47 cases (59.6%) had t(14;18). Bcl‐6 gene rearrangement and extra Bcl‐2 gene signals were found in five and two cases, respectively. Only one had cyclinD1/IgH fusion. Ten of 12 grade 1, nine of 17 grade 2, and 0 of two grade 3 cases had fusion signals, respectively. None of the above abnormalities were detected in 12 of 47 cases (25.5%). Our data confirmed a high frequency of t(14;18) in FL in grade 1, but a lower incidence among grade 2, that could be attributed to the lower incidence of the translocation in FL in Japan. Immunostaining of both Bcl‐2 and CD10 was highly predictable for the presence of t(14;18); the positive predictive value was 75%, suggesting the usefulness of the staining. (Cancer Sci 2005; 96: 77–82)
Reduced expression of Dicer associated with poor prognosis in lung cancer patients
Authors: Karube Yoko , Tanaka Hisaaki , Osada Hirotaka , Tomida Shuta , Tatematsu Yoshio , Yanagisawa Kiyoshi , Yatabe Yasushi , Takamizawa Junichi , Miyoshi Shinichiro , Mitsudomi Tetsuya , Takahashi Takashi
Published: February 2005

Emerging evidence suggests that microRNA, which are well‐conserved, abundant and small regulatory RNA, may be involved in the pathogenesis of human cancers. We recently reported that expression of let‐7 was frequently reduced in lung cancers, and that reduced let‐7 expression was significantly associated with shorter patient survival. Two members of the double‐stranded RNA‐specific endonuclease family, Dicer and Drosha, convert precursor forms of microRNA into their mature forms using a stepwise process. In the present study, we examined expression levels of these genes in 67 non‐small cell lung cancer cases, and found for the first time that Dicer expression levels were reduced in a fraction of lung cancers with a significant prognostic impact on the survival of surgically treated cases. It should be noted that multivariate COX regression analysis showed that the prognostic impact of Dicer (P = 0.001) appears to be independent of disease stage (P = 0.001), while logistic regression analysis demonstrated that the higher incidence of reduced Dicer expression in poorly differentiated tumors remained significant even after correction for other parameters (P = 0.02). Given the fundamental and multiple biological roles of Dicer in various cellular processes, our results suggest the involvement of reduced Dicer expression in the development of lung cancers, thus warranting further investigations of the underlying mechanisms, which can be expected to enhance understanding of the molecular pathogenesis of this fatal cancer. (Cancer Sci 2005; 96: 111–115)
Throwing new light on lung cancer pathogenesis: Updates on three recent topics
Authors: Tomida Shuta , Yatabe Yasushi , Yanagisawa Kiyoshi , Mitsudomi Tetsuya , Takahashi Takashi
Published: February 2005

Lung cancers have become the leading cause of cancer deaths in Japan, claiming more than 55 000 lives annually. Unfortunately, substantial improvement in terms of cure rates has not been achieved over the last two decades, although during the same period of time in‐depth basic knowledge of the molecular mechanisms, which underlies carcinogenesis and progression of this deadly group of neoplasms, has accumulated at an amazing pace. It has consequently become evident that they have many shared but also distinct features, when comparisons are made not only with other common epithelial cancers of adults, such as colon cancer, but also within the various histologic types of lung cancers themselves. This review article provides an up‐date on cutting‐edge research into the following three different topics, from which important new insights have been obtained. The first concerns genetic instability, especially chromosome instability, and checkpoint failure in lung cancers. Second, we deal with EGFR mutations, which shows revealing specificities in various aspects. Finally, advances in the expression profiling analysis of both transcriptomes and proteomes of lung cancers are summarized. (Cancer Sci 2005; 96: 63–68)
Symptomatic efficacy of beidellitic montmorillonite in irritable bowel syndrome: a randomized, controlled trial
Authors: Ducrotte P. , Dapoigny M. , Bonaz B. , Siproudhis L.
Published: February 2005

Background : Beidellitic montmorillonite is a purified clay containing a double aluminium and magnesium silicate.

Aim : To assess the efficacy and the safety of beidellitic montmorillonite (3 g, t.d. for 8 weeks) in patients with irritable bowel syndrome (IBS).

Methods : A multicentre, double‐blind, placebo‐controlled, randomized study with parallel groups, was performed in IBS patients selected according to ROME I criteria. Patients were included after a 1‐week washout period to confirm that abdominal pain and/or discomfort was rated at least 2 on a 0–4 graded Likert scale. Patients were then randomized and stratified according to their predominant bowel habit profile into three groups. The use of rescue medication was allowed: polyethylene glycol 4000 (10–20 g/day) as a laxative agent in case of stool absence for three consecutive days, phloroglucinol (80 to a maximum of 320 mg/day) as a spasmolytic agent for no more than 8 days. The main end‐point was the improvement of abdominal pain and/or discomfort by at least 1 point on the Likert scale.

Results : A total of 524 patients constituted the overall intent‐to‐treat population (ITT), 263 were assessed in the beidellitic montmorillonite group, i.e. 93 diarrhoea‐predominant IBS (D‐IBS), 83 constipation‐predominant IBS (C‐IBS), 87 alternating constipation/diarrhoea‐IBS (A‐IBS); 261 in the placebo group, i.e. 81 D‐IBS, 92 C‐IBS and 88 A‐IBS. Initial analysis in the ITT population demonstrated a higher rate of success with beidellitic montmorillonite (51.7%) when compared with the placebo group (45.2%); however, the difference was not statistically significant. Improvement was significant in C‐IBS both in ITT (beidellitic montmorillonite group = 49.4%, placebo group = 31.5%, P < 0.016) and per protocol populations (59.4% vs. 37.8%) (P < 0.01). The time to improvement of abdominal pain and/or discomfort (log Rank test) was also significantly in favour of beidellitic montmorillonite, (P < 0.04). The average number of stools per day was not different from baseline, either in all patients or in C‐IBS patients. Spasmolytic and laxative agent intakes were not different between the two groups. Subjective evaluation by patients of treatment efficacy and visual analogue scale test of treatment efficacy by investigators were significantly better in the beidellitic montmorillonite group (P < 0.05). Tolerance of beidellitic montmorillonite was considered optimal without any significant adverse event.

Conclusions : Although pain or discomfort was not significantly improved in the entire IBS population treated with beidellitic montmorillonite in comparison with placebo, this study demonstrates that beidellitic montmorillonite is efficient for C‐IBS patients (P < 0.016). This effect of beidellitic montmorillonite on pain cannot be explained by changes in bowel habits. The efficacy of this well‐tolerated therapy warrants further confirmatory therapeutic trials in C‐IBS patients.
Metronidazole and risk of acute pancreatitis: a population‐based case–control study
Authors: Nørgaard M. , Ratanajamit C. , Jacobsen J. , Skriver M. V. , Pedersen L. , Sørensen H. T.
Published: February 2005

Background : Use of metronidazole has been suggested to be associated with an increased risk of acute pancreatitis in case reports.

Aim : To examine this issue within a proper epidemiological design.

Methods : We identified 3083 incident cases of acute pancreatitis from Hospital Discharge Registries in three Danish counties and 30 830 matched population controls. From prescription databases, we extracted information on use of metronidazole with or without concomitant use of proton‐pump inhibitors and/or amoxicillin, macrolides or tetracycline.

Results : Adjusted odds ratios for acute pancreatitis in study subjects who redeemed a prescription for metronidazole within 30, 31–180, or 181–365 days before hospitalization or index date among controls were 3.0 [95% confidence interval (CI): 1.4–6.6], 1.8 (95% CI: 1.2–2.9) and 1.1 (95% CI: 0.6–1.8), respectively. Among subjects with a concomitant prescription for proton‐pump inhibitors and/or amoxicillin, macrolides or tetracycline within 30, 31–180, or 181–365 days before hospitalization, or index date among controls, adjusted odds ratios were 8.3 (95% CI: 2.6–26.4), 2.7 (95% CI: 1.4–5.5), and 1.7 (95% CI: 0.6–4.8), respectively.

Conclusion : Metronidazole may increase the risk of acute pancreatitis. However, the risk seems mainly to increase when metronidazole is used in combination with other drugs used for Helicobacter pylori eradication.
Grown‐up coeliac children: the effects of only a few years on a gluten‐free diet in childhood
Authors: Ciacci C. , Iovino P. , Amoruso D. , Siniscalchi M. , Tortora R. , Di Gilio A. , Fusco M. , Mazzacca G.
Published: February 2005

Aim : To evaluate clinical and psychological status of adults with childhood diagnosis of coeliac disease who were re‐exposed to gluten after only a few years and now on a gluten‐containing diet, compared with adults with recent diagnosis of coeliac disease, and adults who remained on gluten‐free diet after childhood diagnosis.

Methods : A total of 195 adults with a biopsy suggestive of coeliac disease in childhood, who either had adhered to a gluten‐free diet for at least 1 year after diagnosis and now are either on gluten‐free diet (n = 110) or on gluten‐containing diet (n = 85), and adults with newly diagnosed coeliac disease (n = 165) underwent a medical check‐up.

Results : Body mass index and main laboratory indices were statistically different among groups (lowest in never on gluten‐free diet, highest in gluten‐free diet). The lowest average levels of bone mineral density were found among never on gluten‐free diet patients. Prevalence of autoimmune disorders was increased in never on gluten‐free diet when compared with the transient gluten‐free diet and gluten‐free diet groups. Histology revealed villous subatrophy in all patients of never on gluten‐free diet group, in 39 of 110 patients of gluten‐free diet and in 84 of 85 of transient gluten‐free diet groups. Herpetiform dermatitis was found in three patients of gluten‐free diet, three of transient gluten‐free diet and three of never on gluten‐free diet. Dental enamel defects were found in 15 patients of transient gluten‐free diet, 43 of never on gluten‐free diet and in zero of the gluten‐free diet group. Pregnancy outcome was not significantly different between the two groups, but neonatal weight was lower and breast feeding was shorter in the never on gluten‐free diet group. Sexual habits, alcohol intake and cigarette smoking were significantly different in the never on gluten‐free diet group when compared with the other two groups.

Conclusion : Gluten withdrawal in childhood partly protects coeliac adults from clinical and behavioural effects of gluten sensitivity.
Platelet size deviation width, platelet large cell ratio, and mean platelet volume have sufficient sensitivity and specificity in the diagnosis of immune thrombocytopenia
Authors: Kaito Ken , Otsubo Hiroko , Usui Noriko , Yoshida Miyuki , Tanno Jyunko , Kurihara Etsuko , Matsumoto Kozue , Hirata Ryuzo , Domitsu Kenichi , Kobayashi Masayuki
Published: February 2005

We investigated the significance of the platelet indices, mean platelet volume (MPV), platelet size deviation width (PDW), and platelet‐large cell ratio (P‐LCR), in the diagnosis of thrombocytopenia by comparing these levels in 40 patients with hypo‐productive thrombocytopenia (aplastic anaemia; AA) and 39 patients with hyper‐destructive thrombocytopenia (immune thrombo‐cytopenia; ITP). The sensitivity and specificity of platelet indices to make a diagnosis of ITP were also compared. All platelet indices were significantly higher in ITP than in AA, and platelet indices showed sufficient sensitivity and specificity. The area under the curve (AUC) of the receiver operating characteristics curve of platelet indices was large enough to enable the diagnosis of ITP. P‐LCR and PDW had the largest AUCs, which indicated that these values were very reliable for immune thrombocytopenia. Our results suggest that these indices provide clinical information about the underlying conditions of thrombocytopenia. More attention should be paid to these indices in the diagnosis of thrombocytopenia.
Toxicity in standard melphalan–prednisone therapy among myeloma patients with renal failure – a retrospective analysis and recommendations for dose adjustment
Authors: Carlson Kristina , Hjorth Martin , Knudsen Lene Meldgaard ,   The Nordic Myeloma Study Group
Published: February 2005

Haematological and infectious toxicity was correlated to renal function in 272 newly diagnosed myeloma patients given standard dose melphalan–prednisone (MP) as initial treatment without dose adjustment for renal impairment. The glomerular filtration rate (GFR) was estimated by calculated creatinine clearance. Haematological toxicity was found to be significantly related to renal dysfunction. Haematological toxicity World Health Organization (WHO) grades 3–4 after the first MP course was seen in 18%, 28% and 36% of patients with a creatinine clearance of >50, 30–50 and <30 ml/min respectively. WHO grades 3–4 infections occurred in 6% and were not significantly related to renal function. We conclude that MP therapy can be used for initial therapy in myeloma patients with renal impairment but suggest that reduction of the melphalan dose should be considered in patients with a GFR of <30 ml/min. As only 2% of our patients had a clearance of ≤10 ml/min no conclusions can be drawn for this subgroup.
Changes in gene expression profiles of multiple myeloma cells induced by arsenic trioxide (ATO): possible mechanisms to explain ATO resistance in vivo
Authors: Zhou Ping , Kalakonda Nagesh , Comenzo Raymond L.
Published: February 2005

Multiple myeloma (MM) is an incurable plasma cell malignancy marked by eventual resistance to therapy. Although arsenic trioxide (ATO) can induce apoptosis in MM cell lines, the in vivo activity of ATO in MM has been disappointing. The existence of ATO resistance mechanisms in MM can be inferred. We sought to generate hypotheses for ATO resistance by studying the gene expression profiles of MM cells that survived in culture with 0·5 μmol/l ATO. Among the 31 genes whose quantitative levels of expression (QLE) significantly increased in ATO were haem oxygenase 1 (HO‐1) and metallothionein‐2A (MT‐2A). Among the 56 genes whose QLE were significantly decreased were genes that modulate cell cycling [BTBD2 and IGFBP7 (mac25)] and sensitivity to reactive oxygen species (ROS) (BACH2). HO‐1 exerts an anti‐apoptotic effect in ischaemic cells, and MT‐2A chelates ATO intracellularly. Inhibition of HO‐1 with tin protoporphyrin enhances ROS in MM cells in ATO, and addition of N‐acetylcysteine increases MT‐2A. Protective antioxidant responses occur in MM cells exposed to ATO, and may occur in stromal cells as well, and act to quench ROS and provide diffusible anti‐apoptotic factors. They may also involve cysteine‐rich proteins that chelate ATO and modulate redox‐sensitive residues on proteins, such as nuclear factor κB and p53. A better understanding of ATO resistance will enable ATO to be combined with other agents for MM.
Pregnancy improves neutropenia in T‐cell large granular lymphocyte leukaemia
Authors: Osuji Nnenna , Matutes Estella , Dearden Claire , Catovsky Daniel
Published: February 2005

The effect of pregnancy on T‐cell large granular lymphocyte (LGL) leukaemia has not been previously described. We retrospectively reviewed the clinical features of three patients with T‐cell LGL leukaemia; each of them had one or more pregnancies during disease evolution. Pregnancy was associated with sustained improvement in neutrophil count and concurrent reduction in lymphocytosis. Neutropenia returned in the non‐pregnant state in all cases. A similar effect, induced by exogenous progesterone in one patient, suggests a role for progesterone in overcoming mechanisms of neutropenia in this disease. Pregnancy thus appears to have a beneficial effect on neutrophil count in T‐cell LGL leukaemia.
Airway remodelling and inflammation in sheep lungs after chronic airway challenge with house dust mite
Authors: Snibson K. J. , Bischof R. J. , Slocombe R. F. , Meeusen E. N.
Published: February 2005

Background
Remodelling of airway walls is a significant morbidity factor in patients suffering from chronic asthma. The relationship between airway remodelling and the inflammatory response is not well defined. Sheep have been used extensively to model airway disease in humans and represent a suitable model to examine airway remodelling.

Objective
The aim of the present study was to develop a model for airway remodelling in sheep after repeated challenge with a relevant human allergen to assess the relationship of airway remodelling with inflammation.

Methods
Repeated challenges of house dust mite (HDM) extract or saline (control) were administered to local lung segments of sheep for a period of 6 months. After the last challenge, lung tissues from both challenged and unchallenged lung compartments of the same sheep were compared using morphometric image analysis and (immuno) histological studies.

Results
All HDM‐challenged sheep developed significant bronchoalveolar lavage eosinophilia during challenge. At the end of the challenge period, significant increases in airway collagen and airway smooth muscle content were found in a proportion (3/7) of the HDM‐challenged sheep. Hyperplasia of goblet cells and epithelial cells were observed in small bronchi and bronchioles exposed to allergen. Irrespective of airway remodelling changes, all HDM‐challenged, but no saline‐challenged sheep, displayed significant increases in mast cells in alveolar septa and airway walls of challenged lungs compared with untreated lung compartments of the same sheep. Significant increases were also observed in CD5 and γδ T cell subpopulations in all allergen‐exposed lung parenchyma.

Conclusion
A proportion of atopic sheep develop typical airway remodelling changes after chronic allergen challenge, which is not directly related to the level of allergic inflammation.
Individuals with occupational allergy to detergent enzymes display a differential transcriptional regulation and cellular immune response
Authors: Lindstedt M. , Schiött Å. , Johnsen C. R. , Roggen E. , Johansson‐Lindbom B. , Borrebaeck C. A. K.
Published: February 2005

Background
In spite of significant safety measures, allergy to industrial enzymes remains a major concern. The increasing prevalence of occupational allergy emphasizes the need to investigate the functional properties of enzyme‐exposed dendritic cells (DCs), as DCs possess a potent ability to activate allergen‐specific T cells.

Objective
This study aims at elucidating the molecular mechanisms underlying allergic immune responses to lipase, an industrial enzyme. For this purpose, we studied the effect of both hypoallergenic and wild‐type lipase on the transcriptional regulation in DCs and their stimulatory effect on memory CD4+ T cells.

Methods
Five individuals with documented lipase allergy were tested for specific serum IgE. DCs from these individuals, stimulated with lipases, were assayed for their ability to affect proliferation and polarization of memory T cells. The effect of lipases on transcriptional activity in DCs was evaluated using global expression analysis.

Results
Lipase‐specific IgE levels varied considerably between donors, with donor 4 exhibiting highest levels, and a potent specific CD4+ T cell recall response was demonstrated only for donor 4. No difference was detected in cytokine profile when T cells from donor 4 were co‐cultured with DCs pulsed with either hypoallergenic or wild‐type lipase, as demonstrated by high IL‐4 and IL‐13, and low IFN‐γ production. However, the lipases induced different genetic signatures in DCs from donor 4, as compared with the non‐responders.

Conclusions
DCs from individuals with clinically diagnosed allergy to lipase displayed a differential response to stimulation with hypoallergenic and wild‐type lipase in vitro. Only allergen‐pulsed DCs from donor 4 were able to induce CD4+ T cell proliferation. The lipase‐specific T cells displayed a T‐helper type 2 phenotype, which was not altered by hypoallergenic lipase‐pulsed DCs. Furthermore, DCs derived from donor 4 and stimulated with either of the lipases displayed different transcriptional profiles, as compared with the other donors. These signatures represent genes of potential importance for an immunoregulatory role of DC in an ongoing allergic response.
Atopic sensitization and atopic dermatitis in Estonian and Swedish infants
Authors: Voor T. , Julge K. , Böttcher M. F. , Jenmalm M. C. , Duchén K. , Björkstén B.
Published: February 2005

Background
Early life events seem to have a major impact on the development of tolerance or sensitization.

Objective
The aim of the study was to compare the prevalence of sensitization and atopic dermatitis (AD) during the first 2 years of life in Estonia and in Sweden.

Methods
Two groups comprising 110 Estonian and 123 Swedish infants were followed from birth up to 2 years of age. Data about symptoms of allergy, infections and use of antibiotics were obtained by questionnaires. Clinical examinations, skin prick tests (SPTs) with food and inhalant allergens, and blood sampling for IgE analyses were carried out at 3, 6, 12 and 24 months.

Results
The cumulative incidence of AD and positive SPTs were lower in the Estonian than the Swedish infants (14% vs. 24%; P=0.06 and 13% vs. 24%; P=0.03), while circulating IgE antibodies were more common (39% vs. 27%; P=0.06) and often present without any clinical significance in Estonian children. Estonian infants had respiratory illnesses more often and they had received antibiotics more frequently. Use of antibiotics increased the risk for positive SPT in the Estonian (odds ratio=1.7, 95% confidence interval=1.1−2.5), but not in the Swedish infants. This may be explained by the use of broad‐spectrum antibiotics in Estonia, while in Sweden mostly penicillin was prescribed.

Conclusions
The prevalence of AD and positive SPTs was lower in the Estonian than the Swedish infants, while circulating IgE antibodies were more common and often present without any clinical significance. These differences cannot simply be explained by infections, or use of broad‐spectrum antibiotics in the two countries, although more the natural lifestyle in Estonia may be contributing factor.
Oral antihistamines for the symptom of nasal obstruction in persistent allergic rhinitis – a systematic review of randomized controlled trials
Authors: Hore I. , Georgalas C. , Scadding G.
Published: February 2005

Background
Oral antihistamines are recommended by a World Health Organisation working group as a first‐line pharmacological treatment in mild persistent allergic rhinitis. There is, however, uncertainty with respect to their effectiveness for a common symptom, that of nasal obstruction.

Objective
To test the null hypothesis that oral antihistamines have no effect on the symptom of nasal obstruction in a clinical setting in patients with persistent allergic rhinitis.

Methods
Protocol based review of double‐blind randomized controlled trials of oral antihistamine (i.e. drugs considered to act as a histamine receptor type‐1 antagonist) vs. placebo. A search was carried out for published and unpublished trials. Individuals had to be age 12 years or older (with a diagnosis confirmed by skin prick tests, IgE blood tests or nasal allergen challenge), experiencing their normal allergen exposure. A symptom score for nasal obstruction had to be recorded. Predetermined quality criteria were applied. Treating their data as 4‐point scores, a meta‐analysis was carried out for studies, which provided enough data to be pooled.

Results
Meta‐analysis found a weighted mean difference of −0.52 in favour of treatment for patient‐assessed symptom scores (95% confidence interval (CI)−0.73,−0.31, P<0.00001), and of −0.33 in favour of treatment for healthcare worker assessed scores (95% CI −0.49, −0.16, P=0.0001).

Conclusion
Oral antihistamines cause statistically significant improvement in the symptom of nasal obstruction in patients with persistent allergic rhinitis.
Vaccination for birch pollen allergy: comparison of the affinities of specific immunoglobulins E, G1 and G4 measured by surface plasmon resonance
Authors: Jakobsen C. G. , Bodtger U. , Poulsen L. K. , Roggen E. L.
Published: February 2005

Background
Allergen‐specific immunotherapy (SIT) is associated with increased levels of allergen‐specific IgG in serum. However, it is not clear to what extent qualitative changes in the allergen binding capacity of IgG may be induced as well.

Objective
The purpose of this study was to investigate the influences of SIT on antibody affinity.

Methods
The binding affinity of purified serum IgG1, IgG4 and IgE to the major allergen in birch (Betula verrucosa) pollen, Bet v 1, was analysed by surface plasmon resonance. The antibodies were obtained from 10 birch pollen‐allergic patients receiving SIT and from 10 patients with no SIT.

Results
The patients having received SIT have a significant higher titre of anti‐Bet v 1 antibodies in their blood, but the affinity to Bet v 1 of allergen‐specific IgE, IgG1 and IgG4 does not differ between the two groups. For IgG1 and IgG4, correlations between less allergic symptoms and affinity of the antibodies were observed both in the SIT group and to a smaller extent in the non‐SIT group.

Conclusion
SIT has no effect on antibody affinity of allergen‐specific IgE, IgG1 or IgG4. Allergic patients with high‐affinity IgG1 and IgG4 antibodies report less symptoms than patients with low‐affinity antibodies.
Co‐cultivation of mast cells and FcɛRIα+ dendritic‐like cells from human hip bone marrow
Authors: Kaur D. , Berger P. , Duffy S. M. , Brightling C. E. , Bradding P.
Published: February 2005

Background
Mast cells contribute to the pathogenesis of asthma and allergy through the release of a plethora of pro‐inflammatory mediators and cytokines. Their study is hampered by the difficult access to human tissue samples. Human mast cells have been cultured from CD34+ progenitors in the bone marrow of normal volunteers following iliac crest bone marrow biopsy but this is invasive. Hip bone marrow could provide a more convenient less invasive source of mast cell progenitors.

Objective
To characterize mast cells cultured from human bone marrow obtained at routine hip surgery.

Methods
Mononuclear cells were isolated from the bone marrow reamings of patients undergoing routine hip replacement surgery and were cultured with recombinant stem cell factor (SCF), IL‐6 and IL‐10. Cell surface markers were examined using flow cytometry, protease expression monitored using immunohistochemistry, histamine measured by radioenzymic assay, Ca2+ responses analysed using ratiometric Ca2+ imaging, and ion currents recorded via the patch‐clamp technique.

Results
Mast cells were absent at baseline, but accounted for 65±7% of cells after 8–12 weeks of culture, equating to a mean 0.6±0.14 × 106 mast cells per culture. Fifty‐three percent of tryptase+ cells also contained chymase. The remaining cells comprised a population of large CD1a+ HLA‐DR+ and FcɛRIα+ cells, most likely dendritic cells. All mast cells expressed CD117 and the high‐affinity IgE receptor α‐chain (FcɛRIα) constitutively, and developed a Ca2+ response following IgE‐dependent activation. These cells exhibited 7.8±2.9% net IgE‐dependent histamine release, and demonstrated a similar ion channel profile to human lung mast cells. In particular, the intermediate conductance Ca2+‐activated K+ channel opened following IgE‐dependent activation.

Conclusions
Mast cells grown from human hip marrow provide a rich non‐invasive source of functionally mature mast cells. In addition, this culture system may be useful for the generation of FcɛRIα+ dendritic cells.
Molecular cloning of a class IV chitinase allergen from Japanese cedar (Cryptomeria japonica) pollen and competitive inhibition of its immunoglobulin E‐binding capacity by latex C‐serum
Authors: Fujimura T. , Shigeta S. , Suwa T. , Kawamoto S. , Aki T. , Masubuchi M. , Hayashi T. , Hide M. , Ono K.
Published: February 2005

Background
Japanese cedar (Cryptomeria japonica) pollinosis is one of the most prevalent allergic diseases in Japan. Only three C. japonica allergens, Cry j 1, Cry j 2, and CJP‐6, have been characterized. The full IgE‐binding spectrum of C. japonica pollen allergens demonstrates that many allergens remain to be identified.

Objective
The aim of this study was to characterize a novel allergen with a high frequency of IgE binding.

Methods
The cDNA coding for a high‐frequency IgE‐binding protein, designated CJP‐4, was cloned from the total mRNA of C. japonica pollen. The corresponding native allergen was purified by affinity precipitation with colloidal chitin and gel chromatography. The IgE‐binding ability of purified native CJP‐4 was characterized by ELISA and ELISA inhibition.

Results
The CJP‐4 cDNA encoded 281 amino acids with significant sequence homology to class IV chitinases. Purified native CJP‐4, migrated as a homogeneous 34‐kDa protein on SDS‐PAGE, revealed endochitinase activity on native PAGE. The purified protein displayed the ability to bind IgE from all patients tested (31/31) in ELISA, whereas Cry j 1 bound to IgE at a 71% frequency (22/31). Pre‐incubation with latex C‐serum completely inhibited the reaction of pooled sera IgE from patients with C. japonica pollinosis and/or latex allergy to purified CJP‐4.

Conclusion
We identified CJP‐4 as a novel and fourth C. japonica chitinase allergen with high IgE‐binding frequency. The competitive IgE‐binding profile between C. japonica chitinase and latex C‐serum indicated that C. japonica chitinase should be an important pan‐allergen in C. japonica pollen.
Increased plasma levels of matrix metalloproteinase‐9 are associated with the severity of chronic urticaria
Authors: Kessel A. , Bishara R. , Amital A. , Bamberger E. , Sabo E. , Grushko G. , Toubi E.
Published: February 2005

Background
Matrix metalloproteinase (MMP)‐9 is produced by many inflammatory cells such as macrophages, neutrophils, mast cells, eosinophils and T lymphocytes. Activated T cells are capable, through cell–cell contact, of inducing MMP‐9 expression in human mast cells.

Objective
To investigate the activation status of peripheral CD4+ T cells and the level of MMP‐9 in the plasma of patients with chronic urticaria (CU), and whether MMP‐9 levels are in association with CU severity.

Methods
Study subjects included 29 patients with CU and 30 healthy control subjects. At the time of assessment, patients were divided into subgroups according to urticarial severity. Plasma levels of total MMP‐9 (free pro‐MMP‐9 and free MMP‐9) were determined by ELISA. CD4+ lymphocytes were positively selected with magnetic microbeads. After 48 h of activation, CD4+ T cells were assayed for both nuclear factor‐kappaB (NF‐κB) expression and proliferation.

Results
Plasma levels of MMP‐9 were found to be significantly higher in 29 CU patients compared with 18 healthy controls (186±174 vs. 31±21 ng/mL, P<0.0001). We also found a significant correlation between MMP‐9 levels and urticarial severity (r=0.92, P<0.001). In addition, CD4+ T cells from CU patients expressed higher levels of NF‐κB than CD4+ T cells from healthy controls (82±30 vs. 69±20 optical density, P=0.007). Finally, as compared with seven healthy individuals, DNA synthesis in CD4+ T cells from seven CU patients was found to be significantly elevated (1000±240 vs. 751±166 counts per minute, P=0.01).

Conclusion
Increased levels of MMP‐9 are found in CU patients, and particularly among those with severe disease. We also demonstrated that CD4+ T cells from such patients are highly activated.
Natural history of Hymenoptera venom allergy in Eastern Spain
Authors: Fernandez J. , Soriano V. , Mayorga L. , Mayor M.
Published: February 2005

Introduction
The natural history of stings, the clinical reaction of the patient and in vivo and in vitro tests are necessary parameters to assess before initiating Hymenoptera venom immunotherapy. In the decision to initiate immunotherapy with Hymenoptera venom, it is not usual to evaluate the natural history of the disease, which seems to be self‐limiting and therefore of variable clinical significance.

Objectives
Our aim was to determine the natural history of Hymenoptera hypersensitivity over 4 consecutive years in a rural Mediterranean population.

Methods
An epidemiological study of Hymenoptera sting reactions and possible sensitivity was carried out in 145 randomly selected subjects out of a rural Mediterranean population of 600. Seventy‐two subjects, including those with a history of anaphylaxis, completed the 4‐year study. The nature of their clinical reactions, age, sex, history of atopy, profession, family history of reactions to Hymenoptera insects, time elapsed since the last sting, number of stings and specific IgE and IgG were determined (the latter, to the three most important insects in the area: Apis mellifera, Polistes dominulus, and Vespula germanica).

Results
Of the 72 subjects, four subjects had systemic reactions (SR), 23 had large local reaction (LLR) and all the others (117) was minor local reactions. None who had experienced an SR had a repeat SR when re‐stung over the 4‐year study. Of those with LLR, 12 subjects had the same type of reaction and 11 experienced more mild local reactions when re‐stung. In the SR and local reaction groups, IgE to honey bee (Hb) increased significantly during the study period, whereas in those with only LLR, specific IgE to wasp (Polistes) decreased. Specific IgG to Polistes and Vespula (wasps) decreased significantly, whereas there was no change in the specific IgG to Hb in any of the groups. The number of stings per year decreased at the end of the study in all groups, but positive‐specific IgG was higher in subjects with the greatest number of stings. On multivariate analysis using logistic regression, the existence of specific IgE to bee venom, male sex, being an agricultural worker, age of over 16 years and more than five stings per year are seen as individual or co‐factors for developing SR or LLR.

Conclusions
The prevalence of SR was 2.8% in our Mediterranean population. The evolution of IgE and IgG throughout the 4‐year study differed depending on the Hymenoptera studied. Adult male agricultural workers are at greater risk of having SR or LLR, especially when they have specific IgE to Hb and suffer from more than five stings every 4 years.
Allergen‐specific sensitization in asthma and allergic diseases in children: the study on farmers' and non‐farmers' children
Authors: Remes S. T. , Koskela H. O. , Iivanainen K. , Pekkanen J.
Published: February 2005

Background
Farmers' children are less frequently sensitized to common allergens than the non‐farmers' children, but less is known about their sensitization to other allergens and its association with clinical diseases.

Objective
To examine the association of farm environment with atopic sensitization, allergic diseases, expression of allergen‐induced symptoms, and the importance of specific sensitization against ‘common’ (timothy, dog, cat, birch, Dermatophagoides pteronyssimus, mugwort) and ‘other’ (cockroach, horse, Lepidoglyphus destructor, cow) allergens for asthma and allergic diseases in children.

Methods
A cross‐sectional study including 344 farmers' and 366 non‐farmers' children aged 6–13 years in eastern Finland, using a self‐administered written questionnaire and skin prick tests against the above‐mentioned allergens.

Results
Farmers' children had less asthma and allergic diseases and were less often sensitized against common allergens than the non‐farmers' children. However, little difference was observed in sensitization against the other allergens between the farmers' (17.2%) and non‐farmers (14.5%) children [adjusted odds ratios (aOR) 1.11 (0.71–1.72)]. Being sensitized against only other allergens, without sensitization against common allergens, was unrelated to asthma or allergic diseases. Among the single allergens, sensitization against pets or pollen, or against horse or cow, had the strongest association with asthma, hayfever, and atopic eczema; no such association was seen in D. pteronyssimus, mugwort, cockroach, or L. destructor. Farmers' children had significantly less often symptoms of allergic rhinitis in contact with dog (aOR 0.32%, 95% confidence interval (CI) 0.15–0.67), cat (aOR 0.45, 0.22–0.88), or pollen (aOR 0.58%, 95% CI 0.37–0.90) than the non‐farmers' children.

Conclusion
Farm environment reduces the occurrence of asthma, allergic diseases, and atopic sensitization in children, and also the occurrence of allergen‐induced rhinitis. Remarkable differences were observed between single allergens in their association with allergic disease, stressing the importance of allergen selection when defining atopy in epidemiological studies.
Topiramate in long‐term treatment of epilepsy in the intellectually disabled
Authors: Arvio M. , Sillanpää M.
Published: February 2005

Background  To study the effectiveness of topiramate (TPM) in refractory epilepsy in patients who have intellectual disability (ID).

Methods  A representative population sample of 57 patients with ID (age range 2–61, mean 32.8) was administered add‐on TPM for drug‐refractory epilepsy.

Results  Seizure freedom for at least for 6 months was attained by 10 (17%), and seizure reduction of ≥ 50% by further 26 (46%). Less than 50% decrease in seizure frequency was found in 16 (29%). TPM was more efficacious in localisation‐related than in generalised epilepsies (81% vs. 50%, P = 0.019). An at least 50% decrease in seizure frequency was achieved by patients with temporal lobe epilepsy in 100%, continuous spike–waves during sleep syndrome in 75%, Lennox–Gastaut syndrome in 52%, and those with infantile spasms in 25% of cases. As great decrease in seizure frequency was found in most patients with cortical dysplasia (83%), acquired encephalopathy with mesial temporal sclerosis (MTS) (75%), and genetic disease associated with MTS (66%). Adverse effects occurred in 10% including two (3%) with seizure aggravation and three (5%) necessitating discontinuation.

Conclusion  TPM is an effective antiepileptic drug which is of value in treating people with seizures that are resistant to other antiepileptic medication. As a broad‐spectrum drug it may substitute for polypharmacy and, at the same time decrease adverse effects and costs of therapy.
How do persons with intellectual disability manage in the open labour markets? A follow‐up of the Northern Finland 1966 Birth Cohort
Authors: Taanila A. , Rantakallio P. , Koiranen M. , Von Wendt L. , Järvelin M.‐R.
Published: February 2005

Background  The aim was to study how many of the individuals with intellectual disability (ID; IQ ≤ 70) in an age cohort were not receiving a disability pension by the age of 34 years and what their life situation was like in terms of employment, education and morbidity. In 2000, the Northern Finland 1966 Birth Cohort (n = 12 058 live‐born) included 129 individuals with ID.

Method  The outcome data on employment, education, pensions and morbidity were obtained from national registers.

Results  A total of 85.3% (n = 110) of all the individuals with ID were on pension, and 66 of them had severe ID (IQ < 50) and 44 had mild ID (IQ 50–70). Altogether 99 were drawing a pension because of ID, and 11 had a main diagnosis other than ID in the register of Social Insurance Institution. Nineteen individuals with mild ID were not on disability pension. The educational level of those without pension was low, and all whose occupation was known worked in low‐level manual trades in the open labour market. During the past 8 years (1993–2000), their employment rate had been lower and unemployment rate correspondingly higher and unemployment periods longer than those of the reference group (IQ > 85 or not measured). As to the morbidity, they had been hospitalized twice more often than those in the reference group and the mean of their hospitalization days was over fourfold.

Conclusion  More attention should be paid to the vocational education and supported employment services of individuals with ID to help them to manage as independently as possible.
Phylogeography of Daphnia magna in Europe
Authors: DE GELAS K. , DE MEESTER L.
Published: February 2005

The phylogeographical structure of the water flea Daphnia magna in Europe was analysed using a 609‐bp fragment of the cytochrome oxidase subunit I gene. Only moderate overall genetic divergence was detected within Europe. We detected four genetically and, to a large extent, geographically distinct phylogroups within Europe. Our results suggest that these groups recolonized large parts of Europe around 100 000 bp from different refugia. Overall, the pattern suggests a high degree of provincialism with a patchy occurrence of specific lineages, thus confirming the highly subdivided genetic structure usually observed in freshwater zooplankton populations. Although the region around the Mediterranean Sea was only sampled patchily, we obtained strong indications for the occurrence of more divergent genetic lineages in this region. Comparing our European samples to samples from North America and Japan revealed a higher level of differentiation, reflecting limited intercontinental dispersal.
TaqMan DNA technology confirms likely overestimation of cod (Gadus morhua L.) egg abundance in the Irish Sea: implications for the assessment of the cod stock and mapping of spawning areas using egg‐based methods
Authors: FOX C. J. , TAYLOR M. I. , PEREYRA R. , VILLASANA M. I. , RICO C.
Published: February 2005

Recent substantial declines in northeastern Atlantic cod stocks necessitate improved biological knowledge and the development of techniques to complement standard stock assessment methods (which largely depend on accurate commercial catch data). In 2003, an ichthyoplankton survey was undertaken in the Irish Sea and subsamples of ‘cod‐like’ eggs were analysed using a TaqMan multiplex, PCR (polymerase chain reaction) assay (with specific probes for cod, haddock and whiting). The TaqMan method was readily applied to the large number of samples (n = 2770) generated during the survey and when combined with a manual DNA extraction protocol had a low failure rate of 6%. Of the early stage ‘cod‐like’ eggs (1.2–1.75 mm diameter) positively identified: 34% were cod, 8% haddock and 58% whiting. As previous stock estimates based on egg surveys for Irish Sea cod assumed that the majority of ‘cod‐like’ eggs were from cod, the TaqMan results confirm that there was probably substantial contamination by eggs of whiting and haddock that would have inflated estimates of the stock biomass.
Phylogeography of a nematode (Heligmosomoides polygyrus) in the western Palearctic region: persistence of northern cryptic populations during ice ages?
Authors: NIEBERDING C. , LIBOIS R. , DOUADY C. J. , MORAND S. , MICHAUX J. R.
Published: February 2005

This study establishes the continental phylogeographical pattern of a European nematode, Heligmosomoides polygyrus (Dujardin, 1845; Heligmosomoidea). We sequenced 687 base pairs of the mitochondrial DNA (mtDNA) cyt b gene for 136 individuals collected in 22 localities. The results revealed that H. polygyrus populations are separated into five major units corresponding to the Italian, northern European (Denmark and Ireland), Iberian, western European, and Balkan populations. Different subclades were also observed within the first two groups. Based on the rate of molecular evolution of H. polygyrus cyt b gene‐estimated to 3.5%–3.7% divergence per million years (Myr) in a previous study – the isolation time of the five clades was estimated between 2.5 ± 0.24 and 1.5 ± 0.23 million years ago. Moreover, H. polygyrus presents a higher genetic variability in the Mediterranean peninsulas as compared to northwestern Europe, highlighting the role of these regions as refuge areas. Like its specific host, the wood mouse Apodemus sylvaticus, H. polygyrus’ pattern of postglacial recolonization of northwestern Europe was initiated from Iberian populations, while Italian and Balkan populations did not expand to the north. The results also suggest the existence of forested and temperate refuges in the southern British Isles during the Quaternary. Finally, the genetic diversity as well as the level of genetic divergence between the lineages of H. polygyrus are compared to those observed in other vertebrate and invertebrate phylogeographical studies: the existence of highly differentiated lineages in H. polygyrus (5%−10% of genetic divergence) highlights that the effects of Pleistocene climate changes on free‐living organisms are also reflected in their obligate parasites.