bluuebunny/crossref_metadata_2025 huggingface dataset:
Locale and chemistry of spermine binding in the archetypal inward rectifier Kir2.1
Authors: Kurata Harley T. , Zhu Emily A. , Nichols Colin G.
Published: April 2010

Polyamine block of inwardly rectifying potassium (Kir) channels underlies their steep voltage dependence observed in vivo. We have examined the potency, voltage dependence, and kinetics of spermine block in dimeric Kir2.1 constructs containing one nonreactive subunit and one cysteine-substituted subunit before and after modification by methanethiosulfonate (MTS) reagents. At position 169C (between the D172 “rectification controller” and the selectivity filter), modification by either 2-aminoethyl MTS (MTSEA) or 2-(trimethylammonium)ethyl MTS (MTSET) reduced the potency and voltage dependence of spermine block, consistent with this position overlapping the spermine binding site. At position 176C (between D172 and the M2 helix bundle crossing), modification by MTSEA also weakened spermine block. In contrast, MTSET modification of 176C dramatically slowed the kinetics of spermine unblock, with almost no effect on potency or voltage dependence. The data are consistent with MTSET modification of 176C introducing a localized barrier in the inner cavity, resulting in slower spermine entry into and exit from a “deep” binding site (likely between the D172 rectification controller and the selectivity filter), but leaving the spermine binding site mostly unaffected. These findings constrain the location of deep spermine binding that underlies steeply voltage-dependent block, and further suggest important chemical details of high affinity binding of spermine in Kir2.1 channels—the archetypal model of strong inward rectification.
A Hypothesis: Supplementation with Mushroom‐Derived Active Compound Modulates Immunity and Increases Survival in Response to Influenza Virus (H1N1) Infection
Authors: Chunchao Han , Guo Jian-you
Published: April 2010

We hypothesize that the mushroom‐derived active compound may be a potential strategy for increasing survival in response to influenza virus (H1N1) infection through the stimulation of host innate immune response. The validity of the hypothesis can be tested by immune response to influenza infection as seen through survival percentage, virus clearance, weight loss, natural killer cell cytotoxicity, Tumor Necrosis Factor‐α (TNF‐α) and Interferon‐gamma (IFN‐γ) levels, lytic efficiency in the spleens of mice and inducible nitric oxide synthase mRNA expressions in RAW 264.7 murine macrophage cells. The hypothesis may improve people′s quality of life, reduce the medical cost of our healthcare system and eliminate people′s fears of influenza outbreak.
A Single-Electron Reducing Quinone Oxidoreductase Is Necessary to Induce Haustorium Development in the Root Parasitic PlantTriphysaria
Authors: Bandaranayake Pradeepa C.G. , Filappova Tatiana , Tomilov Alexey , Tomilova Natalya B. , Jamison-McClung Denneal , Ngo Quy , Inoue Kentaro , Yoder John I.
Published: April 2010

Parasitic plants in the Orobanchaceae develop haustoria in response to contact with host roots or chemical haustoria-inducing factors. Experiments in this manuscript test the hypothesis that quinolic-inducing factors activate haustorium development via a signal mechanism initiated by redox cycling between quinone and hydroquinone states. Two cDNAs were previously isolated from roots of the parasitic plant Triphysaria versicolor that encode distinct quinone oxidoreductases. QR1 encodes a single-electron reducing NADPH quinone oxidoreductase similar to ζ-crystallin. The QR2 enzyme catalyzes two electron reductions typical of xenobiotic detoxification. QR1 and QR2 transcripts are upregulated in a primary response to chemical-inducing factors, but only QR1 was upregulated in response to host roots. RNA interference technology was used to reduce QR1 and QR2 transcripts in Triphysaria roots that were evaluated for their ability to form haustoria. There was a significant decrease in haustorium development in roots silenced for QR1 but not in roots silenced for QR2. The infrequent QR1 transgenic roots that did develop haustoria had levels of QR1 similar to those of nontransgenic roots. These experiments implicate QR1 as one of the earliest genes on the haustorium signal transduction pathway, encoding a quinone oxidoreductase necessary for the redox bioactivation of haustorial inducing factors.
The roles of plant phenolics in defence and communication during Agrobacterium and Rhizobium infection
Authors: BHATTACHARYA AMITA , SOOD PRIYANKA , CITOVSKY VITALY
Published: April 2010

Phenolics are aromatic benzene ring compounds with one or more hydroxyl groups produced by plants mainly for protection against stress. The functions of phenolic compounds in plant physiology and interactions with biotic and abiotic environments are difficult to overestimate. Phenolics play important roles in plant development, particularly in lignin and pigment biosynthesis. They also provide structural integrity and scaffolding support to plants. Importantly, phenolic phytoalexins, secreted by wounded or otherwise perturbed plants, repel or kill many microorganisms, and some pathogens can counteract or nullify these defences or even subvert them to their own advantage. In this review, we discuss the roles of phenolics in the interactions of plants with Agrobacterium and Rhizobium.
Temporal distribution of phytoplankton in Lake Nyamusingiri in the Albertine Rift Valley, Uganda
Authors: Nyakoojo Clement , Byarujali Stephen M.
Published: April 2010

A study aimed at investigating the temporal variation of phytoplankton assemblages in Lake Nyamusingiri was carried out during the period of December 1997–May 1998. Uganda’s freshwaters are ecologically diverse but a few are intensively studied. Research on phytoplankton has been restricted to large water bodies. There is little information on phytoplankton of the western Uganda crater lakes, which are important water and biodiversity resources. This study provided baseline data on phytoplankton, which will serve as a basis for monitoring the effects of human activities on the lake that might result in ecological transformations like loss of biodiversity because of overexploitation. A laboratory thermometer and Winker’s method were used to determine temperature and dissolved oxygen concentration, respectively. Lake transparency was measured by using the Secchi disc. A Van Dorn sampler was used to collect water samples. Nutrient and chlorophyll a concentrations were determined by using facilities at the Fisheries Resources Research Institute (FIRRI), Jinja. The Sedgwick‐Rafter counting chamber was used to analyse phytoplankton. Variation in temperature was small (25.4–26.2°C). Stable thermal stratification was not evident. The Secchi disc transparency was less than unity. The chlorophyll a value was high. Biomass was found to be light‐limited by nonalgal materials. Dissolved oxygen concentration was more than 100% in the surface waters but declined to <20% at the bottom, which reflected the eutrophic nature of the lake. Diversity indices were low. Eighteen species and five classes of phytoplankton were revealed by this study. The phytoplankton flora was dominated by chlorococcal green algae characteristic of the large eutrophic East African lakes.
Defining the population in need of thromboprophylaxis – making hospitals safer
Authors: Baglin Trevor
Published: April 2010

Venous thromboembolism in adults is related to recent hospitalisation in approximately half of all cases and approximately half of all hospitalised adult patients are considered to be at risk by conventional criteria. Due to advances in surgical practice, the identification of surgical patients in need of prophylaxis has become less rather than more certain. Faster surgical technique, regional anaesthesia and early mobilisation are considered to reduce the risk of venous thromboembolism and hence possibly obviate the need for prophylaxis after early discharge from hospital. An increasing proportion of patients with hospital‐acquired venous thromboembolism are medical patients, but the need to identify medical patients that require thromboprophylaxis is a new aspect of clinical practice for many physicians and prophylaxis remains under‐utilised in non‐surgical hospitalised patients. In this review prevention of hospital‐acquired venous thromboembolism is considered as a patient safety issue in the context of changing clinical practice. Strategies for refining and validating risk assessment models and evaluating the effect of risk assessment and thromboprophylaxis are suggested.
The needs and strengths of unaccompanied asylum‐seeking children and young people in Scotland
Authors: Hopkins Peter , Hill Malcolm
Published: April 2010

Unaccompanied asylum‐seeking children seeking refuge in safer parts of the world have a wide range of needs. This paper discusses the main needs of unaccompanied minors drawing upon the views of service providers who work with or for unaccompanied asylum‐seeking children and young people in Scotland, as well as the perspectives of unaccompanied minors themselves. The complexity of the children's needs is explored with a framework considering their process of resettlement, looking at the present first, the future next and the past last. We also explored the strengths and resilience of the unaccompanied children consulted.
Exploring the care effects of multiple factors on the educational achievement of children looked after at home and away from home: an investigation of two Scottish local authorities
Authors: McClung Michele , Gayle Vernon
Published: April 2010

This paper reports the findings of a research project which explored the care factors that influence the educational achievement of looked‐after children. The project was innovative because it focused on children looked after at home and away from home. A mixed‐methods strategy was adopted to analyse data from two large Scottish local authorities. The project developed, what is to date, the largest dataset which includes variables for one‐fifth of children discharged from care in Scotland over a 5‐year period. The qualitative element of the project collected in‐depth data on the care and education experiences of looked‐after children and care leavers.

The overall finding was that looked‐after children perform less well academically than their counterparts in the general school population. The empirical data indicated that factors such as placement type, reason for becoming looked after and age on becoming looked after were significant in determining educational achievement. Empirical results further indicated that looked‐after children suffered from discrimination and social exclusion in many areas of their lives, including school and where they lived.
Clinical and immunopathological evaluation of epidermolysis bullosa acquisita
Authors: Delgado L. , Aoki V. , Santi C. , Gabbi T. , Sotto M. , Maruta C.
Published: April 2010

Background. Epidermolysis bullosa acquisita (EBA) is a subepidermal blistering disease with IgG antibodies against collagen VII. The disease is heterogeneous and can lead to significant morbidity.

Aim. To characterize the clinical and laboratory profile of patients with EBA from Sao Paulo, Brazil.

Methods. In total, 12 patients (mean age 24 years) were analysed for cutaneous and mucosal involvement, laboratory data and response to treatment.

Results. Mucosal involvement occurred in 11 of the 12 patients (eyes in 4/12, nose in 4/9, pharynx–larynx in 5/9 and oesophagus in 4/10; 3 patients did not undergo nasopharyngeal examination and 2 paediatric patients did not undergo endoscopy). Using direct immunofluorescence, different patterns of deposits were found at the basement membrane zone: IgG (12/12), IgA (6/12), IgM (4/12), C3 (11/12). Indirect immunofluorescence (IIF) was positive in 6 of 12 patients, and IIF on salt-split skin detected dermal deposition in 10 of 12 patients. Antinuclear antibodies were found in 3 of 12 patients, but none of them fulfilled the criteria for systemic lupus erythematosus. After treatment, total remission was achieved in three patients and partial remission in five (three were maintained on minimal treatment, one on the full treatment and one was able to come off treatment). Two patients were lost to follow-up and the remaining two had disease flares. Complications were mainly mucosal (oesophageal stenosis, laryngeal synechia, symblephara and trichiasis).

Conclusions. Mucosal involvement in EBA is a determining factor for disease morbidity. Complete evaluation of the patient, focusing on both cutaneous and extracutaneous sites is essential, as EBA may evolve to refractory disease, severely compromising its outcome.
Vitellogenin gene expression in autogenous Culex tarsalis
Authors: Provost‐Javier K. N. , Chen S. , Rasgon J. L.
Published: April 2010

Autogeny, the ability of a mosquito to mature an initial batch of eggs without blood feeding, is an alternative reproductive strategy with important implications for vector‐borne disease transmission. Regulation of the major yolk protein (vitellogenin; Vg) genes during bloodmeal‐induced oogenesis is well studied, but little is known about regulation of vitellogenesis in autogenous mosquitoes. We characterized the expression of four vitellogenin genes (Vg1a, Vg1b, Vg2a and Vg2b) in an autogenous strain of the West Nile Virus vector, Culex tarsalis. All vitellogenin genes were expressed during autogenous reproduction and following a bloodmeal, although the intensity and duration of expression varied amongst genes. Quantitative PCR analysis of vitellogenin transcription during autogeny revealed a similar temporal pattern to known vitellogenin expression profiles in anautogenous Aedes aegypti. Vitellogenin transcript, primarily produced from the Vg1b gene, was also detected in the larval and pupal stages of development, but no detectable vitellogenin protein was produced during this time period.
Evasion, suppression and tolerance of Drosophila innate immunity by a male‐killing Spiroplasma endosymbiont
Authors: Anbutsu H. , Fukatsu T.
Published: April 2010

How endosymbiotic bacteria cope with host insect immunity is poorly understood. Here we report previously unknown aspects of immunity‐mediated interactions between male‐killing/non‐male‐killing spiroplasmas and Drosophila host. The male‐killing spiroplasma tended to reduce constitutive expression levels of some antimicrobial peptide genes, while the non‐male‐killing spiroplasma did not. In mutant flies whose innate immunity is constitutively up‐regulated, infection densities of the male‐killing spiroplasma were significantly suppressed but managed to increase during the aging of adult flies, indicating that the male‐killing spiroplasma is resistant to mounted immune attacks. These findings suggest that not only immune evasion but also immune suppression and tolerance are involved in the establishment and maintenance of the insect‐microbe symbiotic association.
Bottom‐up versus top‐down control of tree regeneration in the Białowieża Primeval Forest, Poland
Authors: Kuijper Dries P. J. , Cromsigt Joris P. G. M. , Jędrzejewska Bogumiła , Miścicki Stanisław , Churski Marcin , Jędrzejewski Włodzimierz , Kweczlich Iwona
Published: April 2010

1. We tested the interactions between biotic and abiotic factors in structuring temperate forest communities by comparing tree recruitment after 7 years inside 30 pairs of exclosure (excluding ungulates: red deer, roe deer, bison, moose, wild boar) and control plots (7 × 7 m each) in one of the most natural forest systems in Europe, the Białowieża Primeval Forest (eastern Poland). The strictly protected part of that forest hosts the complete native variety in trees, ungulates and their carnivores and excludes human intervention.

2. We analysed whether the exclosure effect interacted with abiotic factors, relevant for tree recruitment (canopy cover, ground vegetation cover, soil fertility and soil wetness) at different stages of tree regeneration (seedlings, saplings ≤ 50 and > 50 cm).

3. Contrary to our expectations, a single factor dominated at each stage of tree regeneration. Herbaceous vegetation cover was the main factor determining the number of seedlings with an optimum at 38% of cover. Soil fertility determined the density of saplings ≤ 50 cm, with on average three times higher density on eutrophic than on oligotrophic soils. Herbivory was the main factor determining recruitment rate of trees into > 50 cm size classes only.

4. The density of saplings that grew into the > 50 cm size class was more than three times higher in the exclosures than in the control plots during 7 years. In the absence of ungulates, on average 3.1 species recruited into the > 50 cm size class compared to 1.7 in control plots. Tree species occurred in more equal proportions inside exclosures, whereas species composition was pushed towards strong dominance of a preferred forage species, Carpinus betulus, in the presence of ungulates. This suggests that preference of species by ungulates can coincide with tolerance to browsing.

5. Synthesis. The study showed that abiotic conditions dominated the early stages and ungulate impact the later stages of tree regeneration, indicating the context‐dependence of herbivore top‐down effects. Heterogeneity in abiotic and biotic conditions may, therefore, have an important influence on the strength of top‐down effects and the role that herbivores play in natural ecosystems.
Accuracy of the water‐siphon test associated to barium study in a high prevalence gastro‐oesophageal reflux disease population: a novel statistical approach
Authors: Fiorentino Eugenio , Matranga Domenica , Pantuso Gianni , Cabibi Daniela , Bonventre Sebastiano , Barbiera Filippo
Published: April 2010

Rationale, aims and objectives Gastro‐oesophageal reflux disease (GORD) is ‘a condition which develops when the reflux of gastric content causes troublesome symptoms or complications’. Instrumental diagnostic tests generally used for GORD are 24‐hour pH‐metry and upper gastrointestinal (GI) endoscopy but barium study associated with provocative manoeuvres such as the water‐siphon test (WST), has also been used for GORD. The aim of this paper was to estimate the accuracy of several tests in patients with GORD in a tertiary care setting, focusing on WST, which is rapid and non‐invasive, simple to perform and well‐tolerated by patients.

Method A total of 172 consecutive patients, symptomatic for reflux referred to a tertiary medical centre, were considered and data regarding the WST, 24‐hour pH‐metry, upper GI endoscopy with histology were analysed using latent class analysis, a multivariable statistical method for estimating the accuracy of tests when a gold standard is not available.

Results The overall proportion of GORD in the sample was estimated at 0.664 [95% confidence interval (CI) = (0.589; 0.731)]. WST proved to be the most sensitive [Se = 0.886; 95% CI = (0.688; 1.000)] compared with pH‐metry [Se = 0.620; 95% CI = (0.493; 0.745)] and endoscopy with histology [Se = 0.534; 95% CI = (0.273; 0.789)]. It was less specific [Sp = 0.537; 95% CI = (0.003; 1.000)] than pH‐metry [Sp = 0.547; 95% CI = (0.281; 0.813)], and even less than endoscopy with histology [Sp = 0.862; 95% CI = (0.495; 1.00)]. Positive predictive values were estimated at 0.792 [95% CI = (0.721; 0.862)] for WST, 0.731 [95% CI = (0.643; 0.819)] for pH‐metry and 0.886 [95% CI = (0.811; 0.961)] for endoscopy with histology. Negative predictive values were estimated at 0.707 [95% CI = (0.573; 0.841)] for WST, 0.422 [95% CI = (0.310; 0.534)] for pH‐metry and 0.484 [95% CI = (0.387; 0.581)] for endoscopy with histology.

Conclusion Water‐siphon test might possibly be useful in patients with suspected GORD because it is highly sensitive and predictive. A positive outcome of the WST associated with a barium study can certainly justify upper GI endoscopy and support any pharmacological treatment of GORD.
Dietary calcium, dairy food intake and metabolic abnormalities in HIV‐infected individuals
Authors: Leite L. H. M. , Sampaio A. B. M. M.
Published: April 2010

Background:  Epidemiological data suggest that calcium intake may influence lipid metabolism. It is unknown whether this influence also occurs in individuals with HIV/AIDS. The present study aimed to assess the relationship between dietary calcium, dairy food intake and metabolic parameters in individuals with HIV/AIDS.

Methods:  A cross‐sectional study was conducted with 100 individuals with HIV/AIDS. Calcium intakes and food group consumption were determined by a food 24‐h dietary recall and a food frequency questionnaire, respectively. The level of physical activity was determined with the international physical activity questionnaire and metabolic syndrome (MS) was defined by National Cholesterol Education Program Adult Treatment Panel III (2001). Student’s t‐test, one‐way analysis of variance and chi‐square were used to compare the groups.

Results:  The mean (SD) calcium intake was 559.5 (298.84) mg day−1 and dairy food consumption was 1.73 (0.78) servings per day. Dietary calcium intake below 700 mg day−1 had greater waist circumference, body mass index (BMI) but not significant and higher systolic blood pressure (SBP) (P < 0.05) and diastolic blood pressure (DBP) (P = 0.07). Dairy food consumers (>2 servings per day) showed lower BMI (P < 0.01), waist circumference (P = 0.05), SBP and DBP (P < 0.05). There was a significant association between calcium intake, MS and hypertension. The odds ratio for MS was 2.0 [95% confidence interval (CI) = 1.23–3.32] and for hypertension was 2.25 (95% CI = 1.44–4.44). Only 21% of the individuals were categorised in the moderate/intense physical activity level.

Conclusions:  The results obtained suggest that a dietary pattern with higher proportion of calcium and fruits/vegetables may protect against abdominal obesity and hypertension in HIV‐infected individuals.
Macromolecules that prefer their membranes curvy
Authors: Huang Kerwyn Casey , Ramamurthi Kumaran S.
Published: April 2010

Understanding the mechanisms that underlie the organization of bacterial cells has become a significant challenge in the field of bacterial cytology. Of specific interest are early macromolecular sorting events that establish cellular non‐uniformity and provide chemical landmarks for later localization events. In this review, we will examine specific examples of lipids and proteins that appear to exploit differences in membrane curvature to drive their localization to particular regions of a bacterial cell. We will also discuss the physical limits of curvature‐mediated localization within bacteria, and the use of modelling to infer biophysical properties of curvature‐sensing macromolecules.
A role for β‐sitosterol to stigmasterol conversion in plant–pathogen interactions
Authors: Griebel Thomas , Zeier Jürgen
Published: April 2010

Upon inoculation with pathogenic microbes, plants induce an array of metabolic changes that potentially contribute to induced resistance or even enhance susceptibility. When analysing leaf lipid composition during the Arabidopsis thaliana–Pseudomonas syringae interaction, we found that accumulation of the phytosterol stigmasterol is a significant plant metabolic process that occurs upon bacterial leaf infection. Stigmasterol is synthesized from β‐sitosterol by the cytochrome P450 CYP710A1 via C22 desaturation. Arabidopsis cyp710A1 mutant lines impaired in pathogen‐inducible expression of the C22 desaturase and concomitant stigmasterol accumulation are more resistant to both avirulent and virulent P. syringae strains than wild‐type plants, and exogenous application of stigmasterol attenuates this resistance phenotype. These data indicate that induced sterol desaturation in wild‐type plants favours pathogen multiplication and plant susceptibility. Stigmasterol formation is triggered through perception of pathogen‐associated molecular patterns such as flagellin and lipopolysaccharides, and through production of reactive oxygen species, but does not depend on the salicylic acid, jasmonic acid or ethylene defence pathways. Isolated microsomal and plasma membrane preparations exhibited a similar increase in the stigmasterol/β‐sitosterol ratio as whole‐leaf extracts after leaf inoculation with P. syringae, indicating that the stigmasterol produced is incorporated into plant membranes. The increased contents of stigmasterol in leaves after pathogen attack do not influence salicylic acid‐mediated defence signalling but attenuate pathogen‐induced expression of the defence regulator flavin‐dependent monooxygenase 1. P. syringae thus promotes plant disease susceptibility through stimulation of sterol C22 desaturation in leaves, which increases the stigmasterol to β‐sitosterol ratio in plant membranes.
Brittle Culm 12, a dual‐targeting kinesin‐4 protein, controls cell‐cycle progression and wall properties in rice
Authors: Zhang Mu , Zhang Baocai , Qian Qian , Yu Yanchun , Li Rui , Zhang Junwen , Liu Xiangling , Zeng Dali , Li Jiayang , Zhou Yihua
Published: April 2010

Kinesins are encoded by a large gene family involved in many basic processes of plant development. However, the number of functionally identified kinesins in rice is very limited. Here, we report the functional characterization of Brittle Culm12 (BC12), a gene encoding a kinesin‐4 protein. bc12 mutants display dwarfism resulting from a significant reduction in cell number and brittleness due to an alteration in cellulose microfibril orientation and wall composition. BC12 is expressed mainly in tissues undergoing cell division and secondary wall thickening. In vitro biochemical analyses verified BC12 as an authentic motor protein. This protein was present in both the nucleus and cytoplasm and associated with microtubule arrays during cell division. Mitotic microtubule array comparison, flow cytometric analysis and expression assays of cyclin‐dependent kinase (CDK) complexes in root‐tip cells showed that cell‐cycle progression is affected in bc12 mutants. BC12 is very probably regulated by CDKA;3 based on yeast two‐hybrid and microarray data. Therefore, BC12 functions as a dual‐targeting kinesin protein and is implicated in cell‐cycle progression, cellulose microfibril deposition and wall composition in the monocot plant rice.
Retracted: Chloroplast stromal proteins, CRR6 and CRR7, are required for assembly of the NAD(P)H dehydrogenase subcomplex A in Arabidopsis
Authors: Peng Lianwei , Cai Wenhe , Shikanai Toshiharu
Published: April 2010

In higher plants, the chloroplast NAD(P)H dehydrogenase (NDH) complex mediates chlororespiration and photosystem I (PSI) cyclic electron transport in thylakoid membranes. Because of its low abundance and fragility, our knowledge on the assembly of chloroplast NDH is very limited, and some nuclear‐encoded factors may be involved in this process. We show here that two Arabidopsis proteins, CHLORORESPIRATORY REDUCTION 6 (CRR6) and CRR7, which were previously identified in mutants specifically defective in NDH accumulation, are present in the stroma, and their stability is independent of the NDH complex, suggesting that they are unlikely to be NDH subunits. Blue native PAGE analysis showed that the accumulation of NDH subcomplex A, which is a core part of NDH that is conserved in divergent species, was specifically impaired in the crr6 and crr7‐1 mutants. However, the expression of plastid‐encoded genes encoding the subcomplex A subunits was not affected, suggesting that CRR6 and CRR7 are involved in post‐translational steps during the biogenesis of subcomplex A. We also discovered that a substantial quantity of NdhH is present in several protein complexes in the chloroplast stroma, possibly as early assembly intermediates of subcomplex A. Although the accumulation of these stromal complexes was not affected in crr6 or crr7‐1, CRR6 was co‐purified with NdhH, implying that CRR6 functions in the later step of subcomplex‐A biogenesis. Accumulation of CRR7 was independent of that of CRR6; we propose that CRR7 functions in a different step in subcomplex‐A biogenesis from CRR6.
Kwashiorkor from a severe dietary restriction in an 8‐month infant in suburban Detroit, Michigan: case report and review of the literature
Authors: Tierney Emily P. , Sage Robert J. , Shwayder Tor
Published: April 2010

Kwashiorkor is a type of protein‐calorie malnutrition often seen in children of impoverished countries and famine. The condition occurs in the setting of insufficient protein intake in the presence of sufficient caloric intake. We report a case of a 8‐month‐old male infant in the suburban Detroit, MI, USA who presented with diffuse edema, erythroderma and desquamation, a “bull‐dog” face, diarrhea, and irritability, consistent with kwashiorkor as a result of severe dietary restriction. The mother had placed the child on a severely restrictive diet, consisting only of RICE DREAM® milk, sweet potatoes and bananas, with the assumption that it would help his rash. Nineteen prior cases of kwashiorkor induced in infants by dietary restriction of “well intending” parents have been reported in the US literature. Malnutrition is often under diagnosed or misdiagnosed in developed countries such as the United States. The results, if unrecognized or untreated, may be devastating. This makes it imperative that physicians consider this diagnosis, recognize potential risk factors and be prepared to accurately assess overall nutritional status of patients.
Atopy, asthma, and lung function in relation to folate and vitamin B12 in adults
Authors: Thuesen B. H. , Husemoen L. L. N. , Ovesen L. , Jørgensen T. , Fenger M. , Gilderson G. , Linneberg A.
Published: April 2010

To cite this article: Thuesen BH, Husemoen LLN, Ovesen L, Jørgensen T, Fenger M, Gilderson G, Linneberg A. Atopy, asthma, and lung function in relation to folate and vitamin B12 in adults. Allergy 2010; 65: 1446–1454.

Background:  Recent studies suggested low serum folate and impaired folate metabolism as potential risk factors for development of asthma and atopic disease, but the results are inconsistent. The aim of this study was to investigate the relations of markers of folate and vitamin B12 (B12) deficiency with different phenotypes of asthma and atopy.

Methods:  A random sample of 6784 persons from a general population aged 30–60 years participated in a health examination in 1999–2001, and 4516 (66.6%) of those also participated in a follow‐up examination 5 years later. The examinations included spirometry, measurements of serum folate and B12, specific IgE to inhalant allergens, total IgE, and genotyping of the MTHFR‐C677T polymorphism – a genetic marker of impaired folate metabolism. Information about dietary intake of folate and B12, asthma diagnosis, and airway symptoms was obtained by questionnaires.

Results:  Low serum folate levels and the TT genotype of the MTHFR‐C677T polymorphism were associated with increased prevalence of self‐reported doctor‐diagnosed asthma [odds ratio (OR) 1.37, 95% confidence interval (CI) 1.05–1.79 and OR 1.52; 95% CI 1.12–2.06, respectively] and attacks of shortness of breath (OR 1.43, 95% CI 1.14–1.79 and OR 1.47; 95% CI: 1.14–1.91, respectively). We found no significant associations with lung function or atopic outcomes. Serum levels of B12 and dietary intake of folate and B12 were not associated with asthma or atopy.

Conclusions:  We found that two objective markers of folate deficiency were associated with self‐reported doctor‐diagnosed asthma and attacks of shortness of breath, but not with lung function or atopy.
Structural lung changes, lung function, and non‐invasive inflammatory markers in cystic fibrosis
Authors: Robroeks Charlotte M. H. H. T. , Roozeboom Marieke H. , De Jong Pim A. , Tiddens Harm A. W. M. , Jöbsis Quirijn , Hendriks Han J. , Yntema Jan‐Bart L. , Brackel Hein L. , Van Gent Rene , Robben Simon , Dompeling Edward
Published: April 2010

Robroeks CMHHT, Roozeboom MH, de Jong PA, Tiddens HAWM, Jöbsis Q, Hendriks HJ, Yntema J‐BL, Brackel HL, van Gent R, Robben S, Dompeling E. Structural lung changes, lung function, and non‐invasive inflammatory markers in cystic fibrosis. Pediatr Allergy Immunol 2010: 21: 493–500. © 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard

Cystic fibrosis (CF) lung disease is characterized by chronic airway inflammation and recurrent infections, resulting in (ir)reversible structural lung changes and a progressive decline in lung function. The objective of this study was to investigate the relationship between non‐invasive inflammatory markers (IM) in exhaled breath condensate (EBC), lung function indices and structural lung changes, visualized by high resolution computed tomography (HRCT) scans in CF. In 34 CF patients, lung function indices (forced expiratory volume in 1 s, forced vital capacity [FVC], residual volume, and total lung capacity [TLC]) and non‐invasive IM (exhaled nitric oxide, and condensate acidity, nitrate, nitrite, 8‐isoprostane, hydrogen peroxide, interferon‐gamma) were assessed. HRCT scans were scored in a standardized and validated way, a composite score and component scores were calculated. In general, the correlations between non‐invasive IM and structural lung changes, and between IM and lung function were low (correlation coefficients <0.40). Patients with positive sputum Pseudomonas cultures had higher EBC nitrite levels and higher parenchymal HRCT subscores than patients with Pseudomonas‐negative cultures (p < 0.05). Multiple linear regression models demonstrated that FVC was significantly predicted by hydrogen peroxide in EBC, and the scores of bronchiectasis and mosaic perfusion (Pearson correlation coefficient R = 0.78, p < 0.001). TLC was significantly predicted by 8‐isoprostane, nitrate, hydrogen peroxide in EBC, and the mucous plugging subscore (R = 0.92, p < 0.01). Static and dynamic lung function indices in this CF group were predicted by the combination of non‐invasive IM in EBC and structural lung changes on HRCT imaging. Future longitudinal studies should reveal whether non‐invasive monitoring of airway inflammation in CF adds to better follow‐up of patients.
The indication and effectiveness of low‐dose erythromycin therapy in pediatric patients with bronchial asthma*
Authors: Korematsu Seigo , Yamamoto Kyoko , Nagakura Tomokazu , Miyahara Hiroaki , Okazaki Naho , Akiyoshi Kensuke , Maeda Tomoki , Suenobu So‐ichi , Izumi Tatsuro
Published: April 2010

Korematsu S, Yamamoto K, Nagakura T, Miyahara H, Okazaki N, Akiyoshi K, Maeda T, Suenobu S‐i, Izumi T. The indication and effectiveness of low‐dose erythromycin therapy in pediatric patients with bronchial asthma. Pediatr Allergy Immunol 2010: 21: 489–492. © 2010 John Wiley & Sons A/S

To elucidate the mechanisms of intractable pediatric bronchial asthma and the indication of low‐dose erythromycin (EM) therapy, the serum chemokine levels of and the angiogenic factor were evaluated in 55 pediatric patients with bronchial asthma; 7.4 ± 3.5 yr old, who had been treated with inhaled steroid, leukotriene receptor antagonist, theophylline and others for more than a year. Both the levels of interleukin (IL) 8 (p = 0.036) and vascular endothelial growth factor (VEGF) (p = 0.005) were higher in patients with severe type than those of patients with the milder type, while other chemokine levels such as serum eotaxin and MCP1 did not show the correlation with the severity of bronchial asthma. Induction of therapy with low‐dose EM induced improvement of the clinical symptoms in patients with severe type and decrease of their serum chemokine levels: IL8; from 736 ± 88 to 75 ± 85 pg/ml (p < 0.0005), and VEGF; from 352.0 ± 160.5 to 132.2 ± 59.9 pg/ml (p = 0.021) within the next 6 months. Moreover, low‐dose EM resulted in a decreased daily peak‐trough fluctuation rate of the serum theophylline concentration; (Cmax − Cmin)/Cmin, from 1.3 ± 0.5 to 0.5 ± 0.3, which led to the maintenance of effective serum levels. These results indicated that IL8 and VEGF affect the severity of standard therapies resistance intractable bronchial asthma. Through the suppression of these chemokines and maintenance of effective theophylline levels, low‐dose EM therapy improves the symptoms of bronchial asthma.
Allergy, total serum immunoglobulin E, and airflow in children and adolescents in TENOR
Authors: Haselkorn Tmirah , Szefler Stanley J. , Simons F. E. R. , Zeiger Robert S. , Mink David R. , Chipps Bradley E. , Borish Larry , Wong Dennis A. ,   for the TENOR Study Group
Published: April 2010

Haselkorn T, Szefler SJ, Simons FER, Zeiger RS, Mink DR, Chipps BE, Borish L, Wong DA, for the TENOR Study Group. Allergy, total serum immunoglobulin E, and airflow in children and adolescents in TENOR. Pediatr Allergy Immunol 2010: 21: 1157–1165. © 2010 John Wiley & Sons A/S

In children and adolescents with difficult‐to‐treat asthma, few data exist characterizing the relationships between basic patient characteristics (e.g., age, sex) and atopic indicators in asthma. These associations were examined in The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR), an observational study of a large cohort of patients with severe or difficult‐to‐treat asthma. To characterize allergy patterns and the relationship between total serum immunoglobulin E (IgE) and airflow in young patients with severe or difficult‐to‐treat asthma. A total of 1261 patients from the TENOR study were stratified into four age groups at baseline (6–8, 9–11, 12–14, and 15–17 yr). The objective was to characterize allergy patterns and the relationship between total serum immunoglobulin E (IgE) and ratio of pre‐bronchodilator forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) in young patients with severe or difficult‐to‐treat asthma. The chi‐square test for categorical variables and analysis of variance for continuous variables were used to identify significant differences among age groups. Multivariable linear regression was used to evaluate the association between IgE and FEV1/FVC. Allergic rhinitis was reported in approximately two‐thirds of patients. Up to 25% of patients had atopic dermatitis, which differed across age groups in boys (p < 0.05). Positive allergen skin test rate differed across age groups in boys (p < 0.05). Rates of asthma triggers were higher and differed across age groups in girls (p < 0.05), particularly around menarche (12–14 yr). IgE levels were higher in boys and differed across age groups in boys (p < 0.01) and girls (p < 0.05). IgE was associated with a lower FEV1/FVC after adjusting for age and sex (p < 0.01). Severe or difficult‐to‐treat asthma in children and adolescents is characterized by high frequencies of comorbid allergic diseases, allergen sensitization, and high IgE levels. This burden is amplified by the association of more airflow limitation with higher IgE levels, suggesting the need for allergy evaluations.
Contact urticaria caused by a fluorescent dye
Authors: Sugiura Keiji , Sugiura Mariko , Sasaki Kazumi , Mori Ayumi
Published: April 2010

A 28‐year‐old man developed urticaria while he was working in the garage. We suspected contact urticaria, which can be caused by some products used in his field, and we carried out a prick test using his work gloves and shoes. His gloves were orange and black in colour, his shoes were black and white in colour, and the materials they were made of were unknown. The results of the prick test using the gloves and shoes were positive. Gas chromatography/mass spectrometry was applied, and a fluorescent dye was found to be present in his gloves and shoes. The results of a prick test using the fluorescent dye were positive. His urticaria improved after he stopped using these gloves and shoes. This was a rare case of contact urticaria caused by a fluorescent dye in clothing.
Review: T helper 17 cells: Their role in glomerulonephritis
Authors: OOI JOSHUA D , KITCHING A RICHARD , HOLDSWORTH STEPHEN R
Published: April 2010

T helper (Th) cells are an integral part of the host's immune response to eliminate invading pathogens. However, autoimmune or ‘autoinflammatory’ diseases can develop if Th cell responses are not effectively regulated. Several subsets of Th cells exist, including the Th17 subset that produces interleukin‐17A, important in experimental models of organ‐specific autoimmune inflammation. Its discovery has explained paradoxical observations in model systems thought to be Th1 mediated but were exacerbated in the absence of interferon‐γ, the prototypic Th1 effector cytokine. Th17 cells express unique transcription factors and secrete a unique pattern of cytokines. Interleukin‐17A induces pro‐inflammatory cytokines and chemokines and mediates neutrophil recruitment. Th17 cells have a reciprocal relationship with T regulatory cells and can also mediate suppression of Th1 responses. Recent studies also suggest that Th17 cells are not terminally differentiated but can switch into Th1 cells. Th17 cells have themselves been recently shown to induce antigen‐specific cell‐mediated proliferative glomerulonephritis. There is increasing evidence implicating Th17 cells in anti‐glomerular basement membrane disease, lupus nephritis and pauci‐immune glomerulonephritis. This review will review the discovery of the Th17 subset, its properties, its relationship with other Th subsets and assess the current evidence implicating Th17 cells in glomerulonephritis.
Involvement of peripheral adenosine 5′‐triphosphate and P2X purinoceptor in pain‐related behavior produced by orthotopic melanoma inoculation in mice
Authors: Fujita Masahide , Andoh Tsugunobu , Sasaki Atsushi , Saiki Ikuo , Kuraishi Yasushi
Published: April 2010

Adenosine 5′‐triphosphate (ATP) plays an important role in nociceptive processing. We used a mouse model of skin cancer pain to investigate the role of ATP in cancer pain. Orthotopic inoculation of B16‐BL6 melanoma cells into the hind paw produced spontaneous licking of the tumor‐bearing paw. Intraperitoneal injection of the P2 purinoceptor antagonist suramin suppressed spontaneous licking dose‐dependently. Two P2X purinoceptor antagonists also suppressed spontaneous licking. An intraplantar injection of ATP, which did not induce licking in the healthy paw, increased licking of the tumor‐bearing paw. Spontaneous firing of the tibial nerve was significantly increased in tumor‐bearing mice and was inhibited by suramin. Extracellular concentration of ATP was significantly increased in the tumor‐bearing paw than in the normal paw. ATP is concentrated in the culture medium of melanoma, lung cancer and breast cancer cells, but not fibroblasts. The P2X3receptor was expressed in about 40% of peripherin‐positive small and medium‐sized neurons in the dorsal root ganglia. P2X3‐positive neurons were significantly increased in melanoma‐bearing mice. These results suggest that ATP and P2X, especially P2X3, receptors are involved in skin cancer pain, due to the increased release of ATP and increased expression of P2X3receptors in the sensory neurons.
Prepare for conflict: EEG correlates of the anticipation of target competition during overt and covert shifts of visual attention
Authors: Kelly Simon P. , Foxe John J. , Newman Geoffrey , Edelman Jay A.
Published: April 2010

When preparing to make a saccadic eye movement in a cued direction, perception of stimuli at the target location is enhanced, just as it is when attention is covertly deployed there. Accordingly, the timing and anatomical sources of preparatory brain activity accompanying shifts of covert attention and saccade preparation tend to exhibit a large degree of overlap. However, there is evidence that preparatory processes are modulated by the foreknowledge of visual distractor competition during covert attention, and it is unknown whether eye movement preparation undergoes equivalent modulation. Here we examine preparatory processes in the electroencephalogram of human participants during four blocked versions of a spatial cueing task, requiring either covert detection or saccade execution, and either containing a distractor or not. As in previous work, a typical pattern of spatially selective occipital, parietal and frontal activity was seen in all task versions. However, whereas distractor presence called on an enhancement of spatially selective visual cortical modulation during covert attention, it instead called on increased activity over frontomedial oculomotor areas in the case of overt saccade preparation. We conclude that, although advance orienting signals may be similar in character during overt and covert conditions, the pattern by which these signals are modulated to ameliorate the behavioral costs of distractor competition is highly distinct, pointing to a degree of separability between the overt and covert systems.
Cutaneous anaesthesia of the lower leg can improve sensibility in the diabetic foot. A double‐blind, randomized clinical trial
Authors: Lundborg G. N. , Björkman A. C. G. , Rosén B. N. , Nilsson J.‐Å. , Dahlin L. B.
Published: April 2010

Diabet. Med. 27, 823–829 (2010)

Aims Impaired sensory function in the sole of the foot in diabetic patients is a substantial problem caused by unknown mechanisms. Hand or foot sensibility can be improved by cutaneous anaesthesia of the forearm or lower leg, respectively, in healthy subjects. Hypothetically, cutaneous anaesthesia induces a silent area in the primary somatosensory cortex, allowing adjacent cortical areas to expand; thus, resulting in enhanced sensory processing. Our aim was to improve sensory function in the foot in Type 1 and Type 2 diabetic patients by application of an anaesthetic cream to the lower leg.

Methods In a double‐blind study, 37 patients with Type 1 or Type 2 diabetes were randomly assigned to cutaneous application of either an anaesthetic cream (EMLA®) or a placebo cream to the skin of the lower leg for 1.5 h. Sensibility at five points of the sole of the foot was assessed before and after 1.5 and 24 h. Vibrotactile sense was also assessed. Primary outcome was change of touch threshold at the first metatarsal head from pretreatment to 1.5 h assessment.

Results Anaesthetic cream on the lower leg resulted in a significant improvement of touch threshold at the first metatarsal head after 1.5 and 24 h. In addition, improvement of touch thresholds was also observed at the other four assessment sites, together with a decreased vibration threshold at 125 Hz.

Conclusions The findings of improved touch thresholds open up new possibilities in treatment of sensibility disturbances in the diabetic foot, using a simple and non‐invasive method.
The potential impact of using glycated haemoglobin as the preferred diagnostic tool for detecting Type 2 diabetes mellitus
Authors: Mostafa S. A. , Davies M. J. , Webb D. , Gray L. J. , Srinivasan B. T , Jarvis J. , Khunti K.
Published: April 2010

Diabet. Med. 27, 762–769 (2010)

Aims  There are calls to simplify the diagnosis of Type 2 diabetes mellitus (T2DM) to reduce the burden of undiagnosed disease. Glycated haemoglobin (HbA1c) is therefore being considered as a preferred diagnostic tool to replace the need for an oral glucose tolerance test (OGTT), considered by many as cumbersome and inconvenient. The aim of this study was to examine the potential impact of the preferred use of HbA1c as a diagnostic tool on the prevalence and phenotype of T2DM.

Methods  Analysis of the Leicester Ethnic Atherosclerosis and Diabetes Risk (LEADER) cohort for previously undiagnosed individuals between 40 and 75 years of age who had OGTT, repeated if within the diabetes range, and HbA1c results. We compared the prevalence and phenotype of subjects with T2DM based on either HbA1c≥6.5% or OGTT using 1999 World Health Organization criteria.

Results  From the total population of 8696, we detected 291 (3.3%) with T2DM from using an OGTT, and 502 (5.8%) had HbA1c≥6.5%. Of those diagnosed with T2DM by OGTT, 93 (1.2%) had HbA1c <6.5% and therefore would not have been classified as having T2DM using proposed criteria. Using HbA1c criteria resulted in 304 (3.5%) additional cases of T2DM, approximately doubling the prevalence. Of these 304 additional people, 172 (56.7%) had impaired glucose tolerance/impaired fasting glycaemia according to 1999 World Health Organization criteria. Using HbA1c criteria there was an increase of 2.2‐ and 1.4‐fold in south Asians and white Europeans detected, respectively.

Conclusions  Within this multi‐ethnic cohort, we found that introducing HbA1c≥6.5% as the preferred diagnostic test to diagnose T2DM significantly increased numbers detected with T2DM; however, some people were no longer detected as having T2DM.