bluuebunny/crossref_metadata_2025 huggingface dataset:
Bullous eosinophilic cellulitis succession with eosinophilic pustular folliculitis without eosinophilia
Authors: ARCA Ercan , KÖSE Osman , KARSLIOĞLU Yildirim , TAŞTAN Halis Bülent , DEMİRİZ Murat
Published: December 2006

Eosinophilic cellulitis is characterized clinically by an acute dermatitis resembling cellulitis with unknown etiology. Eosinophilic pustular folliculitis is also a rare inflammatory dermatosis characterized by recurrent crops of erythematous follicular papulopustules that coalesce to form annular plaques with unclear etiopathogenesis. We describe a 20‐year‐old white male who had vesiculobullous and plaque‐like lesions on the hands and feet and was diagnosed with bullous eosinophilic cellulitis clinically and histologically without any etiological agents. Following therapy with oral corticosteroid and oral tetracycline capsules, the lesions disappeared. After a 2‐month asymptomatic period, the patient developed pruritic follicular papules and pustules on the lower and upper extremities and upper back. Stool examination revealed Gierdia intestinalis eggs. The patient had complete clearance with treatment of ornidazol for 2 weeks and indomethacin for 2 months. This is the first report of bullous eosinophilic cellulitis coexisting with eosinophilic pustular folliculitis without eosinophilia in the English published work.
Tuberculous gumma associated with idiopathic thrombocytopenic purpura: Report of a Japanese female patient
Authors: MAEJIMA Hideki , ARAI Satoru , EBATA Toshiya , TAKEDA Hiroshi , KUSUNOKI Mai , KATSUOKA Kensei
Published: December 2006

Our patient was a 77‐year‐old Japanese woman, who was under treatment for idiopathic thrombocytopenic purpura (ITP) and chronic renal failure. She had warm nodules and cord‐like induration on her left knee that appeared similar to Bazin's erythema induratum. A chest X‐ray examination revealed miliary tuberculosis; after anti‐mycobacterial therapy, the warm nodules and cord‐like induration were transformed into a cold, non‐tender abscess that drained. Histopathological findings showed caseation necrosis in the subcutaneous tissue, however, mycobacteria were directly detected by Ziehl–Neelsen staining from cutaneous lesions, and cultures from the same lesion also grew Mycobacterium tuberculosis. Tuberculous gumma demonstrated multiple, cold, painless abscesses and thrombosis were also seen. This is a rare and unusual clinical form of cutaneous tuberculosis, and the result of hematogenous dissemination from a primary focus during periods of lowered resistance.
Dipalmitoylation of radicicol results in improved efficacy against tumor growth and angiogenesis in vivo
Authors: Oikawa Tsutomu , Onozawa Chizuko , Kuranuki Sachi , Igarashi Yasuhiro , Sato Mayumi , Ashino Hiromi , Shimamura Mariko , Toi Masakazu , Kurakata Shinichi
Published: December 2006

Tumor‐related angiogenesis is likely to be a potential target for the treatment of cancer. One key to develop this angiostatic strategy would be to find useful angiogenesis inhibitors. Here we report the effects of radicicol, a microbial angiogenesis inhibitor that we previously identified using the chorioallantoic membrane assay, and its novel analog, 14,16‐dipalmitoyl‐radicicol, on tumor angiogenesis and growth. As expected for agents containing a penolic hydroxyl group, systemic administration of radicicol had little or no effect on neovascularization triggered by a M5076 mouse tumor cell line or a RMT‐1 rat mammary carcinoma cell line established from autochthonous rat mammary tumors induced by 7,12‐dimethylbenz[a]anthracene in a mouse dorsal air sac assay system. The agent did not show growth‐inhibitory activity against either transplantable M5076 tumors or autochthonous 7,12‐dimethylbenz[a]anthracene‐induced rat mammary tumors. In contrast, 14,16‐dipalmitoyl‐radicicol potently suppressed tumor angiogenesis and growth in these experimental models. Furthermore, the analog significantly prolonged the survival rate of M5076‐implanted mice. Although not stronger than radicicol, it dose‐dependently inhibited embryonic angiogenesis in the chorioallantoic membrane assay, the dose required for half‐maximal inhibition (ID50) value being 23 µg (27 nmol) per egg, and showed concentration‐dependent antiproliferative activity against microvascular endothelial cells in vitro. These data suggest that 14,16‐dipalmitoyl‐radicicol is a promising antitumor agent with antiangiogenic activity. (Cancer Sci 2007; 98: 219–225)
Downregulation of RECK by promoter methylation correlates with lymph node metastasis in non‐small cell lung cancer
Authors: Chang Huang‐Chou , Cho Chun‐Yu , Hung Wen‐Chun
Published: December 2006

In the present study, we addressed the molecular mechanism of the downregulation of reversion‐inducing‐cysteine‐rich protein with Kazal motifs (RECK), a critical tumor suppressor that can potently inhibit angiogenesis and metastasis, in non‐small cell lung cancer and its clinical significance. The methylation status of the RECK gene promoter was studied by methylation‐specific polymerase chain reaction. RECK mRNA and protein levels were investigated by reverse transcription–polymerase chain reaction and western blot analysis. Downregulation of RECK was observed in 60% of the 55 tumors analyzed. Using methylation‐specific polymerase chain reaction analysis methylation of the RECK promoter was detected in 63.6% (35/55) of the tumor tissues. A strong correlation between downregulation and promoter methylation was found in these tumors (P = 0.000005). More importantly, downregulation of RECK significantly correlated with lymph node metastasis (P = 0.038). Mutation of codon 12 of the K‐ras gene was detected in 25.5% (14/55) of lung tumor tissues. Statistical analysis indicated that K‐ras mutation was linked with RECK promoter methylation (P = 0.047) and downregulation (P = 0.023). Promoter methylation was also detected in human lung cancer cell lines, and the DNA methyltransferase inhibitor 5′‐azacytidine reversed the expression of RECK and reduced the invasive ability of these cell lines. Collectively, our results suggest that downregulation of the metastasis suppressor RECK is caused by promoter methylation in non‐small cell lung cancer and is associated with K‐ras mutation and lymph node metastasis. (Cancer Sci 2007; 98: 169–173)
Inverse association between coffee drinking and the risk of hepatocellular carcinoma: a case‐control study in Japan
Authors: Tanaka Keitaro , Hara Megumi , Sakamoto Tatsuhiko , Higaki Yasuki , Mizuta Toshihiko , Eguchi Yuichiro , Yasutake Tsutomu , Ozaki Iwata , Yamamoto Kyosuke , Onohara Shingo , Kawazoe Seiji , Shigematsu Hirohisa , Koizumi Shunzo
Published: December 2006

Coffee use has consistently been associated with lower serum liver enzyme levels and a reduced risk of liver cirrhosis. A limited number of cohort and case‐control studies also suggest a decreased risk of hepatocellular carcinoma (HCC) among coffee drinkers, but mostly without consideration of hepatitis virus infection. In the present case‐control study, we recruited 209 incident HCC cases and three different controls (1308 community controls, 275 hospital controls, and 381 patients with chronic liver disease [CLD] without HCC), all of whom were aged 40–79 years and residents of Saga Prefecture, Japan. A questionnaire survey elicited information on coffee use during the last 1–2 years and 10 years before, and plasma hepatitis B surface antigen and antibodies to hepatitis C virus were tested for all but community controls. After adjustment for sex, age, heavy alcohol use, smoking status and hepatitis virus markers (except for community controls), coffee use during the last 1–2 years was associated with a decreased risk against any control group. For coffee use 10 years before, comparison between HCC cases and either community controls or CLD patients revealed a decreased risk; adjusted odds ratios for occasional use, 1–2 cups/day and ≥3 cups/day compared with no use were 0.33, 0.27 and 0.22 (P trend < 0.001), respectively, against community controls, and 0.86, 0.62 and 0.53 (P trend = 0.05), respectively, against CLD patients. These results suggest that coffee may protect against the development of HCC, yet further elaborate studies (hopefully, intervention studies) are warranted to corroborate these findings. (Cancer Sci 2007; 98: 214–218)
Risk assessment of ritual use of oral dimethyltryptamine (DMT) and harmala alkaloids
Authors: Gable Robert S.
Published: December 2006

Aim  To extend previous reviews by assessing the acute systemic toxicity and psychological hazards of a dimethyltryptamine and β‐carboline brew (ayahuasca/hoasca) used in religious ceremonies.

Method  A systematic literature search, supplemented by interviews with ceremony participants.

Results  No laboratory animal models were located that tested the acute toxicity or the abuse potential of ayahuasca. Separate animal studies of the median lethal dose of dimethyltryptamine (DMT) and of several harmala alkaloids indicated that a lethal dose of these substances in humans is probably greater than 20 times the typical ceremonial dose. Adverse health effects may occur from casual use of ayahuasca, particularly when serotonergic substances are used in conjunction. DMT is capable of inducing aversive psychological reactions or transient psychotic episodes that resolve spontaneously in a few hours. There was no evidence that ayahuasca has substantial or persistent abuse potential. Long‐term psychological benefits have been documented when ayahuasca is used in a well‐established social context.

Conclusion  A decoction of DMT and harmala alkaloids used in religious ceremonies has a safety margin comparable to codeine, mescaline or methadone. The dependence potential of oral DMT and the risk of sustained psychological disturbance are minimal.
A comparative multi‐level analysis of contextual drinking in American and Canadian adults
Authors: Kairouz Sylvia , Greenfield Thomas K.
Published: December 2006

Aim  To investigate the effects of demographic factors and drinking location on contextual drinking in a comparison of US and Canadian adults.

Design  Multi‐level techniques were used to model the two‐level hierarchical structure of drinking contexts (level 1) nested within individuals (level 2).

Participants  Two random samples of current drinkers aged 18 years or older were drawn from Canada's Alcohol and Other Drugs Survey (CADS, 1994) and the 1995 National Alcohol Survey (NAS 9). The US sample included 2304 respondents (level 2) who reported a total of 5956 drinking contexts (level 1); in Canada, 5394 respondents reported 13 235 drinking contexts.

Measurements  Participants reported usual alcohol intake in up to four drinking locations. Demographic data included age, gender, education level, income and marital status.

Findings  Significant variation in usual alcohol intake was observed between drinking locations in both the US and Canada. The full multi‐level models explained 25% of the variance at the contextual level and 25% and 22% at the individual level in the US and Canada. Contextual drinking was determined by a complex relationship between demographic characteristics and drinking locations. Some interactions between locations and demographic variables were observed for both the US and Canada, whereas others were observed only in the US sample.

Conclusions  There is a need, from a population health perspective, for a multi‐level approach in epidemiology and prevention that considers drinking setting as a relevant level for analysis and intervention.
The reliability and validity of the Severity of Dependence Scale for detecting cannabis dependence in psychosis
Authors: Hides L. , Dawe S. , Young R. McD. , Kavanagh D. J.
Published: December 2006

Aims  To determine the reliability and validity of the Severity of Dependence Scale (SDS) for detecting cannabis dependence in a large sample of in‐patients with a schizophrenia spectrum disorder.

Design  Cross‐sectional study.

Participants  Participants were 153 in‐patients with a schizophrenia spectrum disorder in Brisbane, Australia.

Measurements  Participants were administered the SDS for cannabis dependence in the past 12 months. The presence of Diagnostic and Statistical Manual Version‐IV (DSM‐IV) cannabis dependence in the previous 12 months was assessed using the Comprehensive International Diagnostic Interview (CIDI).

Findings  The SDS had high levels of internal consistency and strong construct and concurrent validity. Individuals with a score of ≥2 on the SDS were nearly 30 times more likely to have DSM‐IV cannabis dependence. The SDS was the strongest predictor of DSM‐IV cannabis dependence after controlling for other predictor variables.

Conclusions  The SDS is a brief, valid and reliable screen for cannabis dependence among people with psychosis.
The Indian Ocean dipole – the unsung driver of climatic variability in East Africa
Authors: Marchant Rob , Mumbi Cassian , Behera Swadhin , Yamagata Toshio
Published: December 2006

A growing body of evidence suggests that an independent ocean circulation system in the Indian Ocean, the Indian Ocean dipole (IOD), is partly responsible for driving climate variability of the surrounding landmasses. The IOD had traditionally been viewed as an artefact of the El Niño–Southern Oscillation (ENSO) system although increasingly the evidence is amassing that it is separate and distinct phenomenon. We review the causes of the IOD, how it develops within the Indian Ocean, the relationships with ENSO, and the consequences for East African climate dynamics and associated impacts on ecosystems, in particular along the Eastern Arc Mountains of Kenya and Tanzania. We evaluate current research initiatives focussed on characterizing and constraining the IOD and examine how effective these will be in determining climate change impacts on East African ecosystems and how such predictive capacity can be used in developing policy.
Habitat diversity and fish assemblages in an African river basin (Nyagui River, Zimbabwe)
Authors: Kadye Wilbert T. , Marshall Brian E.
Published: December 2006

Little is known about the ecology of stream fishes in Zimbabwe and this study investigated fish communities in the Nyagui River basin and is one of the first to examine the relationship between fish assemblages and habitat diversity in Zimbabwe. Fourteen sampling stations were, for convenience, divided into three groups; upper (>1400 m above sea level), middle (1000–14000 m) and lower stations (<1000 m). A total of 24 species were collected, four of which were introduced, and the species composition differed according to the location of the stations. Species that favoured running water and/or rocks were generally absent from the upper stations, reflecting the fact that they were mostly sandy‐bottomed and still. Diversity and relative abundance increased in the mid‐ and low‐altitude stations, which were rockier and faster flowing. Both species diversity and relative abundance increased with the catchment area above each station, which was attributed to increased habitat diversity in larger streams. This view was supported by a strong correlation between habitat diversity and catchment area, and between habitat diversity and species richness and relative abundance. At present, the Nyagui system is relatively unregulated but the Kunzvi Dam, presently under construction, will change this situation and species diversity is likely to decrease owing to the loss of rheophilic species while other groups, notably cichlids and introduced species will increase.
Oligogenic transmission of abnormal teat patterning phenotype (ATPP) in cattle
Authors: Ihara N. , Watanabe T. , Sato Y. , Itoh T. , Suzuki T. , Sugimoto Y.
Published: December 2006

Abnormal teat patterning phenotype (ATPP) is characterized by one (moderate form) or two (severe form) absent teats in cattle. Using an allele‐sharing non‐parametric linkage strategy, significant associations with severe ATPP animals were detected on BTA17 (Zmax = 7.3 at 21 cM), centromeric BTA1 (Zmax = 3.7 at 8 cM) and telomeric BTA1 (Zmax = 4.8 at 142 cM). The BTA17 region was also significantly associated in the analysis of the moderate ATPP animals (Zmax = 5.3 at 0 cM). The transmission disequilibrium test in severe ATPP animals demonstrated significant over‐transmission of paternal alleles in the BTA17 region (P = 2.2 × 10−9), the centromeric BTA1 region (P = 0.035) and the telomeric BTA1 region (P = 0.005). Significant over‐transmission of the BTA17 region was also observed among the moderate ATPP animals (P = 2.3 × 10−4). These findings indicate that the BTA17 locus plays a key role in risk of the disease, and that the BTA17 locus contributes temporally in combination with the two other loci on BTA1 and/or possibly unknown modifier(s) in a probabilistic oligo‐ or polygenic manner of transmission. Haplotypes of these three loci can be used for marker‐assisted animal breeding to control the recurrence of affected progeny with ATPP.
A randomised comparison of deferasiroxversusdeferoxamine for the treatment of transfusional iron overload in sickle cell disease
Authors: Vichinsky Elliott , Onyekwere Onyinye , Porter John , Swerdlow Paul , Eckman James , Lane Peter , Files Beatrice , Hassell Kathryn , Kelly Patrick , Wilson Felicia , Bernaudin Françoise , Forni Gian Luca , Okpala Iheanyi , Ressayre‐Djaffer Catherine , Alberti Daniele , Holland Jaymes , Marks Peter , Fung Ellen , Fischer Roland , Mueller Brigitta U. , Coates Thomas ,   the Deferasirox in Sickle Cell Investigators
Published: December 2006

Deferasirox is a once‐daily, oral iron chelator developed for treating transfusional iron overload. Preclinical studies indicated that the kidney was a potential target organ of toxicity. As patients with sickle cell disease often have abnormal baseline renal function, the primary objective of this randomised, open‐label, phase II trial was to evaluate the safety and tolerability of deferasirox in comparison with deferoxamine in this population. Assessment of efficacy, as measured by change in liver iron concentration (LIC) using biosusceptometry, was a secondary objective. A total of 195 adult and paediatric patients received deferasirox (n = 132) or deferoxamine (n = 63). Adverse events most commonly associated with deferasirox were mild, including transient nausea, vomiting, diarrhoea, abdominal pain and skin rash. Abnormal laboratory studies with deferasirox were occasionally associated with mild non‐progressive increases in serum creatinine and reversible elevations in liver function tests. Discontinuation rates from deferasirox (11·4%) and deferoxamine (11·1%) were similar. Over 1 year, similar dose‐dependent LIC reductions were observed with deferasirox and deferoxamine. Once‐daily oral deferasirox has acceptable tolerability and appears to have similar efficacy to deferoxamine in reducing iron burden in transfused patients with sickle cell disease.
See also editorial comment by Anne O'Hare. Acquiring literacy in the face of severe speech and physical impairments
Authors: Pennington Lindsay
Published: December 2006

.
 
O'Hare A.
(
2006
)

,
48
,
628
.
 
DOI: 10.1017/S0012162206001332, published online by Cambridge University Press, 12 July 2006.
Effect of breast feeding on intelligence in children: prospective study, sibling pairs analysis, and meta‐analysis
Authors: Reading Richard
Published: December 2006

.
 
Der G.,
Batty G.D. &
Deary I.D.
(
2006
)

,
333
,
945
.
 
DOI: 10.1136/bmj.38978.699583.55 (published 4 October 2006).

Objective  To assess the importance of maternal intelligence, and the effect of controlling for it and other important confounders, in the link between breastfeeding and children's intelligence.

Design  Examination of the effect of breastfeeding on cognitive ability and the impact of a range of potential confounders, in particular maternal IQ, within a national database. Additional analyses compared pairs of siblings from the sample who were and were not breastfed. The results are considered in the context of other studies that have also controlled for parental intelligence via meta‐analysis.

Setting  1979 US national longitudinal survey of youth.

Subjects  Data on 5475 children, the offspring of 3161 mothers in the longitudinal survey.

Main outcome measure  IQ in children measured by Peabody individual achievement test.

Results  The mother's IQ was more highly predictive of breastfeeding status than were her race, education, age, poverty status, smoking, the home environment, or the child's birthweight or birth order. One standard deviation advantage in maternal IQ more than doubled the odds of breastfeeding. Before adjustment, breastfeeding was associated with an increase of around 4 points in mental ability. Adjustment for maternal intelligence accounted for most of this effect. When fully adjusted for a range of relevant confounders, the effect was small (0.52) and non‐significant (95% confidence interval −0.19 to 1.23). The results of the sibling comparisons and meta‐analysis corroborated these findings.

Conclusions  Breastfeeding has little or no effect on intelligence in children. While breastfeeding has many advantages for the child and mother, enhancement of the child's intelligence is unlikely to be among them.
Chromosome 7p linkage and GPR154 gene association in Italian families with allergic asthma
Authors: Malerba G. , Lindgren C. M. , Xumerle L. , Kiviluoma P. , Trabetti E. , Laitinen T. , Galavotti R. , Pescollderungg L. , Boner A. L. , Kere J. , Pignatti P. F.
Published: December 2006

Background
Several genome scans have reported linkage of markers on chromosome 7p with asthma and related phenotypes in different populations. A fine mapping in Finnish and French‐Canadian populations has associated the GPR154 gene (also known as G‐protein‐coupled receptor for asthma susceptibility, GPRA) with elevated IgE or asthma.

Objective
To confirm chromosome 7p linkage and candidate gene association in Italian families with atopic asthma.

Methods
In a two‐phase approach, we first performed a linkage analysis of chromosome 7, and then a family‐based association study on the GPR154 gene for allergic asthma phenotypes in the Italian population.

Results
The screening of 117 families with 19 microsatellite markers showed potential linkage for elevated IgE (P<0.002 at 22 cM from p‐ter), asthma (P<0.005 at 44 cM), or atopy (P<0.005 at 54 cM). In the second phase of the present study, candidate gene GPR154, which is located in the phase one‐linked region, was investigated in 211 families with seven single nucleotide polymorphisms (SNPs) that tag most haplotype variability, by the pedigree disequilibrium test. Elevated IgE levels were associated with two GPR154 gene SNPs (SNP 546333, P=0.0046; rs740 347, P=0.006), and with haplotypes in the global test (P=0.013). Haplotype analysis performed in nuclear families having at least 1 asthmatic parent showed a significant association with asthma (P=0.0173), atopy (P=0.0058), SPT (P=0.0025), and bronchial hyper reactivity (P=0.0163).

Conclusion
These results support a susceptibility locus for asthma and related phenotypes on chromosome 7, and are in agreement with recent reports suggesting that a common susceptibility factor for atopic manifestations in asthma is likely conferred by the locus containing the GPR154 gene.
Validated safety predictions of airway responses to house dust mite in asthma
Authors: Ravensberg A. J. , Van Rensen E. L. J. , Grootendorst D. C. , De Kluijver J. , Diamant Z. , Ricciardolo F. L. M. , Sterk P. J.
Published: December 2006

Background
House dust mite (HDM) is the most common aeroallergen causing sensitization in many Western countries and is often used in allergen inhalation challenges. The concentration of inhaled allergen causing an early asthmatic reaction [provocative concentration of inhaled allergen causing a 20% fall of forced expiratory volume in 1 s (FEV1)(PC20 allergen)] needs to be predicted for safety reasons to estimate accurately the severity of allergen‐induced airway responsiveness. This can be accomplished by using the degree of non‐specific airway responsiveness and skin sensitivity to allergen.

Objective
We derived prediction equations for HDM challenges using PC20 histamine or PC20 methacholine and skin sensitivity data obtained from patients with mild to moderate persistent asthma and validated these equations in an independent asthma population.

Methods
PC20 histamine or PC20 methacholine, skin sensitivity, and PC20 allergen were collected retrospectively from 159 asthmatic patients participating in allergen challenge trials. Both the histamine and methacholine groups (n=75 and n=84, respectively), were divided randomly into a reference group to derive new equations to predict PC20 allergen, and a validation group to test the new equations.

Results
Multiple linear regression analysis revealed that PC20 allergen could be predicted either from PC20 methacholine only (10log PC20 allergen=−0.902+0.741·10log PC20 methacholine) or from PC20 histamine and skin sensitivity (SS) (10log PC20 allergen=−0.494+0.231·10log SS+0.546·10log PC20 histamine). In the validation study, these new equations accurately predicted PC20 allergen following inhalation of HDM allergen allowing a safe starting concentration of allergen of three doubling concentrations below predicted PC20 allergen in all cases.

Conclusion
The early asthmatic response to inhaled HDM extract is predominantly determined by non‐specific airway responsiveness to methacholine or histamine, whereas the influence of the cutaneous sensitivity to HDM appears to be rather limited. Our new equations accurately predict PC20 allergen and hence are suitable for implementation in HDM inhalation studies.
Detection of airborne allergen (Ole e 1) in relation to Olea europaea pollen in S Spain
Authors: De Linares C. , Nieto‐Lugilde D. , Alba F. , Díaz de la Guardia C. , Galán C. , Trigo M. M.
Published: December 2006

Background
In recent years, it has been demonstrated that the air carries not only airborne pollen but also plant particles of smaller size that have allergenic activity, and, being within the respirable range, these particles can trigger rapid attacks in the lower respiratory tract. The study of particles according to size (0.7–40 μm) could provide valuable information on the real allergenic activity in the atmosphere.

Objective
The purpose of this study was to analyse the dynamics of airborne Olea europaea pollen in contrast to the allergenic activity of Ole e 1 in the atmosphere.

Methods
The analyses were carried out with a Hirst‐type volumetric collector and a cascade impactor simultaneously during the MPS of the olive. The indirect ELISA was used to detect the allergenic activity. The sampling was performed in Granada city centre (S Spain), in the Science Faculty building on the University of Granada from 30 April to 26 June 2005.

Results and conclusions
This research demonstrates that both the allergenic activity as well as the pollen particles follow in a similar curve, except in periods before or succeeding the main Olea pollen season. The study of the distribution of the allergenic particles according to their sizes reveals that the highest concentrations are between 3.3 and <0.7 μm, thus indicating that allergenic activity primarily involves paucimicronic particles.
Increased levels of circulating soluble CD14 but not CD83 in infants are associated with early intestinal colonization with Staphylococcus aureus
Authors: Lundell A‐C. , Adlerberth I. , Lindberg E. , Karlsson H. , Ekberg S. , Åberg N. , Saalman R. , Hock B. , Steinkasserer A. , Hesselmar B. , Wold A. E. , Rudin A.
Published: December 2006

Background
Soluble forms of the monocyte marker CD14 and the mature dendritic cell marker CD83 are plasma proteins with immunoregulatory functions. The physiological stimulus for their production is unclear and their possible role in allergy development is unknown.

Methods
We measured the plasma levels of soluble CD14 (sCD14) and soluble CD83 (sCD83) in 64 Swedish children in relation to intestinal bacterial colonization pattern in a prospective birth cohort. Soluble CD14 and sCD83 levels were quantified by enzyme linked immunosorbent assay in plasma obtained at birth and at 4, 18 and 36 months of age. All major aerobic and anaerobic bacteria were quantified in faecal samples obtained regularly over the first 8 weeks of life. Clinical allergy and IgE levels were evaluated at 18 months of age.

Results
Soluble CD14 in plasma increased during the first 18 months of life while sCD83 peaked at 4 months of age. Children who were perinatally colonized with Staphylococcus aureus had significantly higher levels of sCD14 in plasma at 4 months of age relative to non‐colonized children. The levels of sCD14 were unrelated to colonization with Escherichia coli, other enterobacteria, enterococci, clostridia, Bacteroides, bifidobacteria or lactobacilli. Further, children with food allergy by 18 months tended to have lower levels of sCD14 than healthy children. Plasma levels of sCD83 were not related to either bacterial colonization pattern or allergy development.

Conclusions
Perinatal colonization with S. aureus may trigger the occurrence of sCD14 in plasma, which may influence development of the infantile immune system and risk of allergy development.
Lysophosphatidic acid is detectable in human bronchoalveolar lavage fluids at baseline and increased after segmental allergen challenge
Authors: Georas S. N. , Berdyshev E. , Hubbard W. , Gorshkova I. A. , Usatyuk P. V. , Saatian B. , Myers A. C. , Williams M. A. , Xiao H. Q. , Liu M. , Natarajan V.
Published: December 2006

Background
Lysophosphatidic acid (LPA) is a biologically active lysophospholipid and a component of normal plasma. LPA binds to receptors expressed on circulating and structural lung cells and affects cell growth and activation. Whether LPA is present in the lung has not been previously reported.

Objective
To develop an assay to measure LPA in bronchoalveolar lavage (BAL) fluids, and to study the association between LPA and allergic airway inflammation.

Methods
Seventeen allergic subjects underwent bronchoscopy and segmental allergen challenge, followed 18 h later by BAL. Supernatants were analysed for LPA content using liquid chromatography and mass spectroscopy. Expression of LPA receptors on primary bronchial epithelial cells was analysed by immunolabelling, and the effects of LPA on epithelial cell barrier function was investigated by measuring transepithelial resistance.

Results
LPA was detectable in BAL from control lung segments, and significantly increased 18 h after allergen challenge. Polyunsaturated species of LPA were especially increased following segmental allergen challenge. LPA levels did not strongly correlate with the number or percentages of eosinophils, neutrophils of lymphocytes, whereas MIP‐3α (CCL20) levels correlated significantly with the allergen‐driven influx of lymphocytes. The levels of LPA from control sites correlated inversely with BAL protein content, suggesting that LPA promoted epithelial barrier integrity at baseline. Experiments using primary human bronchial epithelial cells confirmed that LPA tightened the epithelial cell barrier.

Conclusion
Lysophosphatidic acid is detectable in human BAL fluids at baseline and its expression increases during allergic inflammation. LPA does not appear to be a dominant chemoattractant for eosinophils or lymphocytes during allergic airway inflammation. In the absence of ongoing inflammation, LPA may promote epithelial barrier integrity.
Does skin prick test reactivity to purified allergens correlate with clinical severity of peanut allergy?
Authors: Peeters K. A. B. M. , Koppelman S. J. , Van Hoffen E. , Van Der Tas C. W. H. , Den Hartog Jager C. F. , Penninks A. H. , Hefle S. L. , Bruijnzeel‐Koomen C. A. F. M. , Knol E. F. , Knulst A. C.
Published: December 2006

Background
Recognition of specific peanut allergens or the diversity of IgE binding to peanut allergens may play a role in the elicitation of severe allergic reactions.

Objective
To investigate whether sensitization to individual allergens Ara h 1, Ara h 2, Ara h 3 and Ara h 6 is correlated with clinical severity.

Methods
The reactivity of purified peanut allergens was measured by skin prick test (SPT) and by IgE immunoblot in 30 patients. The results were related to the clinical reactivity by history, and in 25 of them to the eliciting dose (ED).

Results
The majority of patients recognized Ara h 2 and Ara h 6. Patients with severe symptoms had a higher SPT response to Ara h 2 and Ara h 6 at low concentrations (0.1 μg/mL) and to Ara h 1 and Ara h 3 at higher concentrations (100 μg/mL), compared with patients with mild symptoms. They also recognized a greater number of allergens and showed a higher cumulative SPT response compared with patients with mild symptoms. No significant differences were observed between patients with a low or high ED.

Conclusions
Ara h 2 and Ara h 6 appeared to be more potent than Ara h 1 and Ara h 3. Both SPT reactivity to low concentrations of Ara h 2 and Ara h 6 and to higher concentrations of Ara h 1 and Ara h 3 were shown to be indicative of severe symptoms.
Probiotic‐induced suppression of allergic sensitization and airway inflammation is associated with an increase of T regulatory‐dependent mechanisms in a murine model of asthma
Authors: Feleszko W. , Jaworska J. , Rha R‐D. , Steinhausen S. , Avagyan A. , Jaudszus A. , Ahrens B. , Groneberg D. A. , Wahn U. , Hamelmann E.
Published: December 2006

Background
Microbial intestinal colonization in early in life is regarded to play a major role for the maturation of the immune system. Application of non‐pathogenic probiotic bacteria during early infancy might protect from allergic disorders but underlying mechanisms have not been analysed so far.

Objective
The aim of the current study was to investigate the immune effects of oral application of probiotic bacteria on allergen‐induced sensitization and development of airway inflammation and airway hyper‐reactivity, cardinal features of bronchial asthma.

Methods
Newborn Balb/c mice received orally 109 CFU every second day either Lactobacillus rhamnosus GG or Bifidobacterium lactis (Bb‐12) starting from birth for consecutive 8 weeks, during systemic sensitization (six intraperitoneal injections, days 29–40) and airway challenge (days 54–56) with ovalbumin.

Results
The administration of either Bb‐12 or LGG suppressed all aspects of the asthmatic phenotype: airway reactivity, antigen‐specific immunoglobulin E production and pulmonary eosinophilia (mean: 137 vs. 17 and 13 cells × 103/mL, respectively). Antigen‐specific recall proliferation by spleen cells and T‐helper type 2 cytokine production (IL‐4, IL‐5 and IL‐10) by mesenteric lymph node cells also showed significant reduction, while TGF production remained unchanged. Oral LGG administration particularly suppressed allergen‐induced proliferative responses and was associated with an increase in numbers of TGF‐β‐secreting CD4+/CD3+ T cells in mesenteric lymph nodes (6.5, 16.7%) as well as nearly 2‐fold up‐regulation of Foxp3‐expressing cells in peribronchial lymph nodes.

Conclusions
Neonatal application of probiotic bacteria inhibits subsequent allergic sensitization and airway disease in a murine model of asthma by induction of T regulatory cells associated with increased TGF‐β production.
Retinol concentrations after birth are inversely associated with atopic manifestations in children and young adults
Authors: Pesonen M. , Kallio M. J. T. , Siimes M. A. , Ranki A.
Published: December 2006

Background
Vitamin A has anti‐inflammatory and immunomodulatory effects, and its deficiency results in impaired specific and innate immunity. Vitamin A is essential for inducing the gut‐homing specificity on T cells.

Objective
As an impaired gut immune response in early infancy may contribute to the development of atopic sensitization, we looked for an association of plasma retinol concentrations and the subsequent development of allergic symptoms in healthy infants.

Methods
A cohort of 200 unselected, full‐term newborns were followed up from birth to age 20 years. The plasma retinol concentration was determined in cord blood (n=97), at ages of 2, 4 and 12 months (n=95), and at ages 5 years (n=155) and 11 years (n=151). The subjects were re‐examined at the ages of 5, 11 and 20 years with assessment of the occurrence of allergic symptoms during the preceding year, skin prick testing and measurement of serum total IgE.

Results
Subjects with allergic symptoms or a positive skin prick test (SPT) in childhood or adolescence had lower retinol concentrations in infancy and childhood than symptom‐free subjects. The difference was most pronounced at age 2 months. Retinol concentration at 2 months correlated inversely with positive SPT at ages of 5 and 20 years, and with allergic symptoms at age 20 years.

Conclusion
Retinol concentration in young infants is inversely associated with the subsequent development of allergic symptoms. We propose that an inborn regulation of retinol may play a role in atopic sensitization, possibly through regulating the intestinal T cell responses.
Lipopolysaccharide inhalation exacerbates allergic airway inflammation by activating mast cells and promoting Th2 responses
Authors: Murakami D. , Yamada H. , Yajima T. , Masuda A. , Komune S. , Yoshikai Y.
Published: December 2006

Background
Bacterial infection occasionally exacerbates asthma, although the cellular and molecular mechanisms have not been well defined. An involvement of mast cells has been suggested, as lipopolysaccharides (LPS)‐induced cytokine production from mast cells in vitro.

Objective
This study was undertaken to examine the effects of LPS inhalation on mast cell functions and allergen‐specific immune responses in a murine model of asthma.

Methods
Female BALB/c mice or mast cell‐deficient W/Wv mice were immunized intraperitoneally with ovalbumin (OVA). Mice were challenged with aerosolized OVA or OVA with LPS daily from day 21 to day 24. Twenty‐four hours after the last challenge, airway inflammation and OVA‐specific immune responses were examined. Allergen‐specific T cell responses were further analysed by adoptively transferring OVA‐specific CD4+ T cells. Expression of chemokines in the lung was also examined.

Results
LPS inhalation with OVA resulted in exacerbated airway infiltration, which was not evident in mast cell‐deficient mice. IL‐5 production by mast cells in the lung was enhanced by LPS inhalation. OVA‐specific IgE production as well as proliferation, cytokine production and local infiltration of OVA specific T‐helper lymphocytes type 2 (Th2) were also enhanced. Up‐regulated expression of Th2‐ and/or eosinophil‐attracting chemokines was observed in the lung of mice inhalated with LPS.

Conclusions
LPS inhalation exacerbates airway inflammation, which is accompanied by mast cell activation and enhanced Th2 responses. These observations provide clues towards understanding the mechanisms of bacterial infection‐induced exacerbation of the clinical features of asthma.
Ingestion of heat‐treated Lactobacillus rhamnosus GG prevents development of atopic dermatitis in NC/Nga mice
Authors: Sawada J. , Morita H. , Tanaka A. , Salminen S. , He F. , Matsuda H.
Published: December 2006

Background
Continuous oral administration of live Lactobacillus rhamnosus GG (L. GG) to pregnant subjects with atopic dermatitis and their children, suppressed the frequency of atopic dermatitis. The details of mechanisms and immune systems involved in this suppressive effect, however, remain speculative.

Objective
We sought to clarify suppressive mechanisms of L. GG on atopic dermatitis by using NC/Nga mice, a model of human atopic dermatitis.

Methods
Maternal mice and infant mice were fed with food containing or not containing heat‐treated L. GG during pregnancy and breastfeeding, and after weaning.

Results
Control NC/Nga mice raised under an air‐uncontrolled condition spontaneously manifested typical skin lesions very similar to those in patients with atopic dermatitis. On the other hand, administration of food containing heat‐treated L. GG inhibited the onset and development of atopic skin lesions, accompanied by smaller numbers of mast cells and eosinophils in the affected skin sites. Mice fed with L. GG showed a significant increase in plasma IL‐10 levels compared with control mice, while there was no significant difference in the proportion of splenic CD4+CD25+ regulatory T cells between mice fed with L. GG and control mice. The IL‐10 mRNA expression was enhanced in both Peyer's patches and mesenteric lymph nodes in mice fed with L. GG.

Conclusion
These findings suggest that some components of heat‐treated L. GG may have an ability to delay the onset and suppress the development of atopic dermatitis, probably through a strong induction of IL‐10 in intestinal lymphoid organs and systemic levels.
Effects of dissolved organic matter and ultraviolet radiation on the accrual, stoichiometry and algal taxonomy of stream periphyton
Authors: FROST PAUL C. , CHERRIER CHRISTY T. , LARSON JAMES H. , BRIDGHAM SCOTT , LAMBERTI GARY A.
Published: December 2006

1. We investigated the effects of dissolved organic matter (DOM) and ultraviolet‐B (UVB) radiation on periphyton during a 30‐day experiment in grazer‐free, outdoor artificial streams. We established high [10–12 mg carbon (C) L−1] and low (3–5 mg C L−1) concentrations of DOM in artificial streams exposed to or shielded from ambient UVB radiation. Periphyton was sampled weekly for ash‐free dry mass (AFDM), chlorophyll (chl) a , algal biovolume, elemental composition [C, nitrogen (N) and phosphorus (P)], and algal taxonomic composition.

2. Regardless of the UVB environment, increased DOM concentration caused greater periphyton AFDM, chl a and total C content during the experiment. Increased DOM also significantly increased periphyton C : P and N : P (but not C : N) ratios throughout the experiment. Algal taxonomic composition was strongly affected by elevated stream DOM concentrations; some algal taxa increased and some decreased in biomass and prevalence in artificial streams receiving DOM additions. UVB removal, on the other hand, did not strongly affect periphyton biomass, elemental composition or algal taxonomic composition for most of the experiment.

3. Our results show strong effects of DOM concentration but few, if any, effects of UVB radiation on periphyton biomass, elemental composition and algal taxonomic composition. The effects of DOM may have resulted from its absorption of UVA radiation, or more likely, its provision of organic C and nutrients to microbial communities. The strong effects of DOM on periphyton biomass and elemental composition indicate that they potentially play a key role in food web dynamics and ecosystem processes in forested streams.
The multifarious effects of dispersal and gene flow on contemporary adaptation
Authors: GARANT DANY , FORDE SAMANTHA E. , HENDRY ANDREW P.
Published: December 2006

Dispersal and gene flow can have a variety of interacting effects on evolution. These effects can either promote or constrain adaptive divergence through either genetic or demographic routes. The relative importance of these effects is unknown because few attempts have been made to conceptually integrate and test them.

We draw a broad distinction between situationswithvs.withoutstrong coevolutionary dynamics. This distinction is important because the adaptive peak for a given population is more mobile in the former than in the latter. This difference makes ongoing evolutionary potential more important in the presence of strong coevolutionary dynamics than in their absence.

We advance a conceptual integration of the various effects of gene flow and dispersal on adaptive divergence. In line with other authors, but not necessarily for the same reasons, we suggest that an intermediate level of gene flow will allow the greatest adaptive divergence.

When dispersal is quite low, we predict that an increase will have positive effects on adaptive divergence, owing to genetic/demographic rescue and ‘reinforcement.’ The rescue effect may be more important in small populations and in homogeneous environments. The reinforcement effect may be more common in large populations and in heterogeneous environments.

Once a certain level of dispersal is reached, we predict that a further increase may have negative effects on adaptive divergence. These effects may arise if carrying capacity is exceeded or maladaptive genes are introduced.

Many additional effects remain to be integrated into this framework, and doing so may yield novel insights into the factors influencing evolution on ecological time‐scales.
Participation of XPB/Ptr8p, a component of TFIIH, in nucleocytoplasmic transport of mRNA in fission yeast
Authors: Mizuki Fumitaka , Namiki Takeshi , Sato Hiroshi , Furukawa Hiromi , Matsusaka Tadao , Ohshima Yasumi , Ishibashi Ryoko , Andoh Tomoko , Tani Tokio
Published: December 2006

To identify novel factors involved in nuclear mRNA export in Schizosaccharomyces pombe, we isolated and characterized the ptr8+ gene, mutation of which causes nuclear accumulation of poly (A)+ RNA. The ptr8+ gene encodes an S. pombe homologue of human XPB, a component of TFIIH involved in nucleotide excision repair (NER) and transcription. A temperature‐sensitive mutant of ptr8+ (ptr8‐1) was highly sensitive to UV irradiation, as are human XPB cells. Northern blot analysis demonstrated that the amount of total poly (A)+ mRNAs does not decrease significantly at the nonpermissive temperature in ptr8‐1 cells, whereas a pulse‐labeling assay using 35S‐methionine showed that protein synthesis decreases rapidly after incubation of cells at the nonpermissive temperature, suggesting that ptr8‐1 cells have a defect in nuclear mRNA export. In Saccharomyces cerevisiae, a mutation in the SSL2 gene encoding a homologue of Ptr8p also causes a block of mRNA export at the nonpermissive temperature. In addition, expression of human XPB in ptr8‐1 cells rescued the ts phenotype and the mRNA export defects, suggesting that human XPB may also play a role in mRNA export. Furthermore, we revealed a functional interaction between Ptr8p and Tho2p, a component of the TREX complex involved in mRNA export. These results suggest that XPB/Ptr8p plays roles not only in NER and transcription, but also plays a conserved role in mRNA export.
Cys669–Cys713 disulfide bridge formation is a key to dystroglycan cleavage and subunit association
Authors: Watanabe Noriyuki , Sasaoka Toshikuni , Noguchi Satoru , Nishino Ichizo , Tanaka Torahiko
Published: December 2006

Dystroglycan (DG) is a widely expressed, transmembrane glycoprotein complex that plays important roles by connecting the extracellular matrix to the cytoskeleton. The α‐ and β‐DG subunits are produced by the cleavage of residues 653 and 654 of the precursor. To clarify the mechanisms involved in cleavage and subunit association, we performed a series of mutation analyses and made the following discoveries: (i) Disruption of the intramolecular disulfide bridge between Cys669 and Cys713 in β‐DG completely abolishes the cleavage, (ii) deletions in the loop region (669–713) and in the C‐terminal region of α‐DG (550–645) abolish the cleavage, (iii) disruption of the disulfide bridge and deletions in the loop region deteriorate the α‐ and β‐DG subunit association, and (iv) at the cleavage site, especially, positions P1′ (Ser654) and P6′ (Trp659) are critical. Thus, the critical role of the Cys669–Cys713 disulfide bridge formation is, most likely, to form a specific tertiary structure, in which the α‐ and β‐DG domains interact and the cleavage site becomes susceptible to proteolytic reactions. The Cys669 and Cys713 pair is broadly conserved in vertebrates and in some invertebrates, suggesting that the disulfide bridge formation was established early in the evolution of DG.