bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of a Novel Chitosan Gel on Mucosal Wound Healing Following Endoscopic Sinus Surgery in a Sheep Model of Chronic Rhinosinusitis
Authors: Athanasiadis Theo , Beule Achim G. , Robinson Brian H. , Robinson Simon R. , Shi Z. , Wormald Peter‐John
Published: May 2008

Introduction: Postoperative bleeding and adhesion formation remain the two major problems after endoscopic sinus surgery (ESS). This study investigates the effect on adhesion formation and wound healing in a sheep model of chronic sinusitis of three topical agents: recombinant tissue factor (rTF, Dade Innovin, Marburg, Germany), poly‐ethylene glycol (SprayGel, Confluent Surgical, Waltham, MA), and a novel chitosan‐dextran derivative gel (CD, Department of Chemistry, University of Otago, Dunedin, New Zealand).

Methods: Twenty sheep with chronic sinusitis underwent ESS with standardized mucosal injuries created on the lateral nasal wall and the ethmoid region. Injured areas were divided into four groups, and one of the three agents or control (no treatment) was randomly applied. The presence and severity of adhesions were noted and the healing was evaluated by taking brushings for ciliary beat frequency and biopsies of the injured regions at day 28, 56, 84, and 112 post initial surgery. The biopsy specimens were assessed for re‐epithelialisation using light microscopy and scanning electron microscopy for reciliation. The cytobrush specimens assessed cilial function by measuring ciliary beat frequency.

Results: CD significantly decreased lateral nasal wall and ethmoidal adhesions compared to tissue factor at all time points (5% vs. 25%, and 0 vs. 50%, respectively). There was a noticeable trend toward decreased adhesions on the lateral nasal wall and ethmoids in the SprayGel group (10% and 14%) and the CD group (10% and 0%) compared to controls (15% and 40%). The CD group had a significantly greater percentage of re‐epithelialisation at day 28 and day 84 compared to the rTF group (70% vs. 33%, P < .001; 84.5% vs. 61%, P < 0.05). At day 28, the CD group was significantly more ciliated than control (62% vs. 31%, P < .01) and than rTF (62% vs. 23%, P < .001). This difference between CD and rTF reciliation remained significant at day 56 (67% vs. 40%, P < .05). In addition, the mean cilial grade for CD at day 112 was significantly better than control (1.9 vs. 2.7, P < .05).

Conclusion: In the sheep model of chronic sinusitis, CD significantly improves microscopic wound healing and reduces adhesion formation after ESS.
Temporal trends in the discovery of human viruses
Authors: Woolhouse Mark E.J , Howey Richard , Gaunt Eleanor , Reilly Liam , Chase-Topping Margo , Savill Nick
Published: May 2008

On average, more than two new species of human virus are reported every year. We constructed the cumulative species discovery curve for human viruses going back to 1901. We fitted a statistical model to these data; the shape of the curve strongly suggests that the process of virus discovery is far from complete. We generated a 95% credible interval for the pool of as yet undiscovered virus species of 38–562. We extrapolated the curve and generated an estimate of 10–40 new species to be discovered by 2020. Although we cannot predict the level of health threat that these new viruses will present, we conclude that novel virus species must be anticipated in public health planning. More systematic virus discovery programmes, covering both humans and potential animal reservoirs of human viruses, should be considered.
Sex differences in spatial cognition in an invertebrate: the cuttlefish
Authors: Jozet-Alves Christelle , Modéran Julien , Dickel Ludovic
Published: May 2008

Evidence of sex differences in spatial cognition have been reported in a wide range of vertebrate species. Several evolutionary hypotheses have been proposed to explain these differences. The one best supported is the range size hypothesis that links spatial ability to range size. Our study aimed to determine whether male cuttlefish (
Sepia officinalis
; cephalopod mollusc) range over a larger area than females and whether this difference is associated with a cognitive dimorphism in orientation abilities. First, we assessed the distance travelled by sexually immature and mature cuttlefish of both sexes when placed in an open field (test 1). Second, cuttlefish were trained to solve a spatial task in a T-maze, and the spatial strategy preferentially used (right/left turn or visual cues) was determined (test 2). Our results showed that sexually mature males travelled a longer distance in test 1, and were more likely to use visual cues to orient in test 2, compared with the other three groups. This paper demonstrates for the first time a cognitive dimorphism between sexes in an invertebrate. The data conform to the predictions of the range size hypothesis. Comparative studies with other invertebrate species might lead to a better understanding of the evolution of cognitive dimorphism.
Mitotic CDKs control the metaphase–anaphase transition and trigger spindle elongation
Authors: Rahal Rami , Amon Angelika
Published: June 2008

Mitotic cyclin-dependent kinases (CDKs) control entry into mitosis, but their role during mitotic progression is less well understood. Here we characterize the functions of CDK activity associated with the mitotic cyclins Clb1, Clb2, and Clb3. We show that Clb–CDKs are important for the activation of the ubiquitin ligase Anaphase-Promoting Complex/Cyclosome (APC/C)–Cdc20 that triggers the metaphase–anaphase transition. Furthermore, we define an essential role for Clb–CDK activity in anaphase spindle elongation. Thus, mitotic CDKs serve not only to initiate M phase, but are also needed continuously throughout mitosis to trigger key mitotic events such as APC/C activation and anaphase spindle elongation.
Identification of novel genes involved in light-dependent CRY degradation through a genome-wide RNAi screen
Authors: Sathyanarayanan Sriram , Zheng Xiangzhong , Kumar Shailesh , Chen Chun-Hong , Chen Dechun , Hay Bruce , Sehgal Amita
Published: June 2008

Circadian clocks regulate many different physiological processes and synchronize these to environmental light:dark cycles. In Drosophila, light is transmitted to the clock by a circadian blue light photoreceptor CRYPTOCHROME (CRY). In response to light, CRY promotes the degradation of the circadian clock protein TIMELESS (TIM) and then is itself degraded. To identify novel genes involved in circadian entrainment, we performed an unbiased genome-wide screen in Drosophila cells using a sensitive and quantitative assay that measures light-induced degradation of CRY. We systematically knocked down the expression of ∼21,000 genes and identified those that regulate CRY stability. These genes include ubiquitin ligases, signal transduction molecules, and redox molecules. Many of the genes identified in the screen are specific for CRY degradation and do not affect degradation of the TIM protein in response to light, suggesting that, for the most part, these two pathways are distinct. We further validated the effect of three candidate genes on CRY stability in vivo by assaying flies mutant for each of these genes. This work identifies a novel regulatory network involved in light-dependent CRY degradation and demonstrates the power of a genome-wide RNAi approach for understanding circadian biology.
The temporal dynamics of consolidation and reconsolidation decrease during postnatal development
Authors: Languille Solène , Gruest Nadège , Richer Paullette , Hars Bernard
Published: June 2008

The temporal dynamics of consolidation and reconsolidation of taste/odor aversion memory are evaluated during rat pup growth at postnatal days 3, 10, and 18. This is assessed through the temporal gradients of efficacy of a protein synthesis inhibitor (anisomycin) in inducing amnesia after either acquisition (consolidation) or reactivation (reconsolidation). The results show a progressive reduction with age of the delay during which the inhibitor is able to induce amnesia. Control experiments rule out a reduction of anisomycin efficacy due to blood brain barrier growth or decrease in protein synthesis inhibition. Thus, these results present the first evidence that the protein synthesis-dependent phase of memory stabilization requires less time with age. This decrease occurs in parallel for consolidation and reconsolidation. Such changes in the dynamics of memory processing could contribute to the cognitive improvement associated with development.
In-Gel S-Pyridylethylation of Gel-Resolved Proteins: Whole Gel Method
Authors: Simpson Richard J.
Published: June 2008

INTRODUCTION

This protocol describes a method for performing reduction and S-alkylation of Coomassie-blue-stained proteins within an intact gel. Reduction is performed with dithiothreitol, and alkylation with 4-vinylpyridine. (Treatment of free cysteines with 4-vinylpyridine yields the S-β-(4-pyridylethyl) cysteinyl derivative.) S-β-(4-pyridylethyl) cysteine-containing peptides can be readily identified during RP-HPLC by their characteristic absorbance at 254 nm and during electrospray ionization tandem mass spectrometry by the appearance of a characteristic pyridylethyl fragment ion of 106 Da. The position of cysteine residues in a polypeptide sequence can be determined either by mass spectrometry or as phenylthiohydantoin S-β-(4-pyridylethyl) cysteine during Edman degradation.
Using Gaps and Gap Penalties to Optimize Pairwise Sequence Alignments
Authors: Mount David W.
Published: June 2008

INTRODUCTION

To obtain the best possible alignment between two sequences, it is necessary to include gaps in sequence alignments and use gap penalties. For aligning DNA sequences, a simple positive score for matches and a negative score for mismatches and gaps are most often used. To score matches and mismatches in alignments of proteins, it is necessary to know how often one amino acid is substituted for another in related proteins. In addition, a method is needed to account for insertions and deletions that sometimes appear in related DNA or protein sequences. To accommodate such sequence variations, gaps that appear in sequence alignments are given a negative penalty score reflecting the fact that they are not expected to occur very often. Mathematically speaking, it is very difficult to produce the best-possible alignment, either global or local, unless gaps are included in the alignment. This article discusses how to use gaps and gap penalties to optimize pairwise sequence alignments.
Calycosiphonia pentemara sp. nov. (afrotropical Rubiaceae) from the ‘Lower Guinea’ area
Authors: Sonké Bonaventure , Djuikouo K Marie‐Noël , Robbrecht Elmar
Published: May 2008

A distinctive new species of Calycosiphonia (Rubiaceae) is described and illustrated. It is endemic to the Lower Guinea Domain of the Guineo‐Congolian Region, where it is restricted to south Cameroon and Monte Alén National Park (Equatorial Guinea). Its conservation status is assessed as vulnerable according to the Red list criteria of IUCN. Calycosiphoniapentamera sp. nov. is the third species known from the genus. Molecular data have recently shown that the genera Calycosiphonia and Argocoffeopis form a single clade, but leave some open questions on how to distinguish and delimit the two genera. In the present state of knowledge, the novelty should be placed in Calycosiphonia based on morphological evidence: shrubs with large leaves becoming blackish in the dried state, inflorescences axillary and paired at the nodes, and fruits exceeding 15 mm in diameter. The 5‐merous condition of the flowers and the presence of standard anthers (without transverse septa in the thecae) in C. pentamera are features not previously recorded from the genus. They require a better understanding in the framework of a more robust molecular phylogeny, allowing character analysis of the Calycosiphonia/Argocoffeopsis clade.
Heterosamara sect. Villososperma comb. nov. (Polygalaceae) from eastern Asia
Authors: Castro Sílvia , Silveira Paulo , Coutinho António P. , Paiva Jorge
Published: May 2008

In this study, three species of Polygala L. (Polygalaceae) are transferred to the genus Heterosamara Kuntze based on plant morphology, habitat, and palynological features. Heterosamara wattersii (Hance) Paiva & P. Silveira comb. nov., H. caudata (Rehder & E. H. Wilson) Paiva & P. Silveira comb. nov. and H. resinosa (S. K. Chen) Paiva & P. Silveira comb. nov. from tropical and sub‐tropical forests of eastern Asia are described. The first two are also illustrated and described palynologically. The inclusion of these species within this genus is justified by their typical heteropolar pollen with bilateral symmetry, bilobate crest (appendage in the keel), large lanceolate leaves with petioles, and forest habitats. The lack of information on the flower morphology of H. resinosa makes the classification of this species more difficult, as it is only known from the type specimen. Nonetheless, the habit, habitat and seed morphology place it in the same taxonomic group as the other species studied. The seeds of these three species present very distinctive features within the genus Heterosamara placing them in a newly recognized section, Heterosamara sect. Villososperma (C. Y. Wu & S. K. Chen) Paiva & P. Silveira comb. nov. Identification keys are provided for the genera, sections and species studied.
Acquired pure red cell aplasia: updated review of treatment
Authors: Sawada Kenichi , Fujishima Naohito , Hirokawa Makoto
Published: May 2008

Pure red cell aplasia (PRCA) is a syndrome characterized by a severe normocytic anaemia, reticulocytopenia, and absence of erythroblasts from an otherwise normal bone marrow. Primary PRCA, or secondary PRCA which has not responded to treatment of the underlying disease, is treated as an immunologically‐mediated disease. Although vigorous immunosuppressive treatments induce and maintain remissions in a majority of patients, they carry an increased risk of serious complications. Corticosteroids were used in the treatment of PRCA and this has been considered the treatment of first choice although relapse is not uncommon. Cyclosporine A (CsA) has become established as one of the leading drugs for treatment of PRCA. However, common concerns have been the number of patients treated with CsA who achieve sustained remissions and the number that relapse. This article reviews the current status of CsA therapy and compares it to other treatments for diverse PRCAs.
Risk factors for early death in neonates with Down syndrome and transient leukaemia
Authors: Muramatsu Hideki , Kato Koji , Watanabe Nobuhiro , Matsumoto Kimikazu , Nakamura Tomohiko , Horikoshi Yasuo , Mimaya Junichi , Suzuki Chizuko , Hayakawa Masahiro , Kojima Seiji
Published: May 2008

Transient leukaemia (TL) in neonates with Down syndrome (DS) is characterized by the transient appearance of blast cells in the peripheral blood that resolves spontaneously. Some TL patients die at an early age due to organ failure. Seventy DS patients with TL were studied retrospectively to identify clinical and laboratory characteristics associated with early death (<6 months of age). Sixteen of 70 patients (22·9%) died early. The main causes of death were organ failure, particularly hepatic and cardiopulmonary failure. On univariate analysis, early gestational age (EGA), high white blood cell (WBC) count (≥100 × 109/l), percentage of peripheral blasts, elevated aspartate transaminase (AST), elevated direct bilirubin (DB), and low Apgar score were significantly associated with poor survival. On multivariate analysis, EGA, WBC count, and DB were independent predictors of poor outcome. A simple risk stratification system combining EGA and WBC count was devised to predict poor outcome. Term infants (EGA ≥ 37 weeks) whose WBC count was lower than 100 × 109/l had the best outcome [7·7% (3/39) died early], while preterm infants (EGA < 37 weeks) whose WBC count was higher than 100 × 109/l had the worst outcome [54·5% (6/11) died early]. This stratification system may be useful for identifying high‐risk patients who need early therapeutic interventions.
Fibroblast activation protein α identifies mesenchymal stromal cells from human bone marrow
Authors: Bae Sohyun , Park Chae Woon , Son Hye Kyung , Ju Hye Kyung , Paik Donggi , Jeon Choon‐Ju , Koh Gou Young , Kim Jaeseob , Kim Hoeon
Published: May 2008

Mesenchymal stromal cells (MSCs) have gained widespread popularity in cell therapy, but their development into clinical products has been impeded by the scarcity of cell‐specific markers. We previously explored transcriptome and membrane proteome of MSCs, from which fibroblast activation protein α (FAP) was recognized as a prime surface marker candidate. The present study showed that FAP was constitutively expressed on MSCs, but not on other cells. FAP immunoselection yielded homogeneous MSCs from cryopreserved bone marrow (BM). These results suggest that FAP serves as a surface protein marker that can singly define MSCs from BM and possibly from other sources.
Type 1 von Willebrand disease: application of emerging data to clinical practice
Authors: COLLINS P. W. , CUMMING A. M. , GOODEVE A. C. , LILLICRAP D.
Published: May 2008

Summary.  There has been much recent data published on type 1 von Willebrand disease (VWD) predominantly from three multi‐centre cohort studies. These data have influenced a revision of the classification of type 1 VWD and have important implications for the management of this disorder. Patients with low von Willebrand factor (VWF) levels tend to have VWF mutations and VWD is transmitted predictably within families. In patients with VWF levels close to the lower end of the normal range, candidate mutations are found less often, ABO blood group is a more important factor and the disease has variable heritability within families. The importance of bleeding symptoms, in addition to VWF levels, in the diagnosis of type 1 VWD has been highlighted.
Human dendritic cells infected with an adenoviral vector suppress proliferation of autologous and allogeneic T cells
Authors: Newton Katy R. , Sala‐Soriano Emma , Varsani Hemlata , Stephenson John R. , Goldblatt David , Wedderburn Lucy R.
Published: May 2008

Dendritic cells (DCs) play a key role in the type and course of an immune response. The manipulation of human DCs to produce therapeutic agents by transduction with viral vectors is a growing area of research. We present an investigation into the effects of adenoviral vector infection on human DCs and other cell types, and on their subsequent ability to induce T‐cell proliferation. We show that infection with replication‐deficient adenovirus results in impaired proliferation of T cells in a mixed lymphocyte reaction (MLR). We show this to be an active suppression rather than a defect in the DCs as T cells also fail to proliferate in response to phytohaemagglutinin in the presence of adenoviral vector‐infected DCs. This suppression is not attributable to phenotypic changes, death or inability of the DCs to produce cytokines on stimulation. By separation of DCs from T cells, and addition of conditioned supernatants, we show that suppression is mediated by a soluble factor. Blocking of interleukin (IL)‐10 but not transforming growth factor (TGF)‐β could overcome the suppressive effect in some donors, and the source of the suppressive IL‐10 was lymphocytes exposed to conditioned supernatant. Together our data suggest that infection of DCs by adenoviral vectors leads to suppression of the resulting immune response.
Resource partitioning for soil phosphorus: a hypothesis
Authors: Turner Benjamin L.
Published: May 2008

Organic phosphorus is abundant in soil and its turnover can supply a considerable fraction of the phosphorus taken up by natural vegetation. Despite this, the ecological significance of organic phosphorus remains poorly understood, which is remarkable given the biological importance of phosphorus in terrestrial environments.

Of particular interest is the possibility that coexisting plant species partition soil organic phosphorus to reduce competition. This seems likely given the large number of biologically available phosphorus compounds that occur in soil and the variety of mechanisms by which plants can utilize them.

Here I propose a conceptual model of resource partitioning for soil phosphorus. The model describes a hypothetical example of four coexisting plant species that differ in their ability to access soil organic phosphorus compounds, which are grouped to form a gradient of biological availability based on the processes involved in their utilization by plants.

Synthesis: Resource partitioning for soil phosphorus could provide an additional mechanism to explain the coexistence and distribution of plant species. It is likely to occur widely in terrestrial environments, but should have greatest ecological significance wherever productivity is limited by the availability of soil phosphorus. This includes freshwater wetlands, super‐humid temperate regions and ecosystems developed on strongly‐weathered soils that cover vast areas of ancient landscapes in Africa, Australia and South America.
Biological Flora of the British Isles: Paris quadrifolia L.
Authors: Jacquemyn Hans , Brys Rein , Hutchings Michael J.
Published: May 2008

This account reviews information on all aspects of the biology of Paris quadrifolia L. (herb Paris) that are relevant to understanding its ecological characteristics and behaviour. The main topics are presented within the framework of the Biological Flora of the British Isles: distribution, habitat, communities, responses to biotic factors, responses to environment, structure and physiology, phenology, floral and seed characters, herbivores and disease, history and conservation.

Paris quadrifolia is a perennial woodland herb that is found across the boreal and temperate areas of Europe. In the UK, it is a native species of moist, mostly ancient woodlands on calcareous soils. It can occasionally be found in grikes on open limestone pavement. It is absent from both very dry and very wet sites. It flowers and fruits most freely in the open stages of the coppice cycle, but persists in deep shade.

Paris quadrifolia is a rhizomatous geophyte. Regeneration is both by vegetative spread and sexual reproduction, and heavily weighted towards the former strategy. Paris quadrifolia has a monopodial growth form, with the increments of several years of growth remaining connected along the rhizome. Branching of the rhizome is sometimes observed. Amylose (a component of starch and a major storage carbohydrate) concentrations are low in young rhizome segments, but significantly higher in older segments. Severing rhizome connections by removing the oldest segments results in reduced growth and significantly smaller distal shoots, indicating that the size of the clonal fragment determines vigour of the terminal shoot and that integration serves to maintain the vitality of the rhizome, particularly in resource‐poor environments.

Flowers are pollinated by wind, or self‐pollinated. Insect pollination is very rare. Seed dispersal is limited and rates of spread vary between 0.21 and 0.33 m year−1.

As in most other European countries, Paris quadrifolia has declined in the UK. Many sites were lost in northern England and central Scotland before 1930, and since then there has been some decline in south‐east England because of the destruction of broad‐leaved woodland and planting of conifers. Since the species colonizes new forest stands very slowly, management should focus mainly on conservation of ancient forest stands.
The everyday life of adolescent coeliacs: issues of importance for compliance with the gluten‐free diet
Authors: Olsson C. , Hörnell A. , Ivarsson A. , Sydner Y. M.
Published: May 2008

Background  Noncompliance with the gluten‐free diet is often reported among adolescents with coeliac disease. However, knowledge is limited regarding their own perspectives and experiences of managing the disease and the prescription of a gluten‐free diet. The aim of this study was to explore how adolescents with coeliac disease perceive and manage their everyday lives in relation to a gluten‐free diet.

Methods  In total, 47 adolescents with coeliac disease, divided into 10 focus groups, were interviewed. In the qualitative analysis, themes emerged to illustrate and explain the adolescents’ own perspectives on life with a gluten‐free diet.

Results  The probability of compliance with the gluten‐free diet was comprised by insufficient knowledge of significant others, problems with the availability and sensory acceptance of gluten‐free food, insufficient social support and their perceived dietary deviance. Three different approaches to the gluten‐free diet emerged: compliers, occasional noncompliers, and noncompliers. Each approach, as a coping strategy, was rational in the sense that it represented the adolescents’ differing views of everyday life with coeliac disease and a prescription of a gluten‐free diet.

Conclusions  Adolescents with coeliac disease experience various dilemmas related to the gluten‐free diet. The study demonstrated unmet needs and implies empowerment strategies for optimum clinical outcomes.
Knowledge, compliance and serum phenylalanine concentrations in adolescents and adults with phenylketonuria and the effect of a patient‐focused educational resource
Authors: Durham‐Shearer S. J. , Judd P. A. , Whelan K. , Thomas J. E.
Published: May 2008

Background  There is a lack of dedicated resources for adolescent and adult patients with phenylketonuria (PKU) and few studies have examined dietary practices within this group.

Methods  One hundred and seventy‐seven PKU patients were sent questionnaires to assess dietary compliance and the preferred format for an educational resource. Seventy‐one patients responded; 32 following diet were recruited to assess the resource’s impact on test variables. The results were compared for the intervention group (n = 22) and control group (n = 10) at baseline, and 1 and 6 months after resource intervention.

Results  Most patients were aware of dietary recommendations, although this did not always result in compliance. The preferred resource format was a filofax‐style folder with inserts (P < 0.05). There was a significant difference in the extent of change in knowledge score between baseline and 1 month in favour of the intervention group (P < 0.05). The improvement in knowledge was not accompanied by a significant improvement in measures of compliance.

Conclusions  These findings add to the knowledge base about this patient group and support the use of patient involvement in resource development. It is likely that the test parameters used were not sensitive enough to pick up subtle and longer‐term effects on compliance.
Kisspeptin: A Novel Regulator of Reproductive Function
Authors: Dhillo W. S.
Published: May 2008

Young Neuroendocrinologists Prize Reviews

Michael Harbuz Young Investigator Prize Lecture

The UK and international neuroendocrine community was deeply shocked and saddened the unbelievably premature death of Michael Harbuz in Bristol in 2006. Mick was a superb friend and colleague, and played a huge part in the development and activities of the British Neuroendocrine Group/British Society for Neuroendocrinology (BSN), serving as both Membership Secretary and Treasurer between 1999 and 2004. Mick was a leader in the field of neuroendocrine–immune interactions, and brought a great deal of charisma, humour and ability to meetings and conferences. He was also a passionate and committed supporter of the progress of young researchers and of their participation in neuroendocrine events. He recognised that today’s postgraduate students and postdoctoral research fellows are tomorrow’s neuroendocrine researchers, be it in academia, the health services or industry.

To recognise Mick’s great commitment to and enthusiasm for postgraduate education both in the University of Bristol and in the BSN, we decided to honour and remember him by instituting the ‘Michael Harbuz Young Investigator Prize Lecture’ to be delivered annually. Dr Waljit Dhillo from Imperial College London was the inaugural recipient of this award, and presented his lecture at the Annual Meeting of the BSN in Nottingham in September 2007, upon which this review is based.

Recent evidence demonstrates that the neuropeptide kisspeptin and its receptor, GPR54, have a fundamental role in initiating the onset of puberty and are important in regulating reproductive function. This review discusses the evidence available from animals and humans demonstrating that kisspeptin potently stimulates the release of gonadotrophins by stimulating the release of gonadotrophin‐releasing hormone and that a lack of kisspeptin or GPR54 results in reproductive failure.
Bone marrow‐derived mesenchymal stem cells are capable of mediating hepatitis B virus infection in injured tissues
Authors: Rong Q. , Zhang L. , Su E. , Li J. , Li J. , Liu Z. , Huang Z. , Ma W. , Cao K. , Huang J.
Published: May 2008

Summary.  We have previously showed that endothelial progenitor cells (EPCs) through uptake of hepatitis B virus (HBV) may play a critical role in mediating extrahepatic HBV diseases. However, it remains to be elucidated whether mesenchymal stem cells (MSCs) are capable of mediating HBV trans‐infection into extrahepatic tissues. Methods and Results: In this study, we showed that HBV antigens, HBV DNA and the viral particles were detected in MSCs after 3 days virus challenge. Neither HBV covalently closed circular DNA nor pregenomic RNA were detected in MSCs. Intravenously transplantation of HBV‐exposed MSCs into myocardial infarction mouse model resulted in incorporation of HBV into injured heart and other damaged tissues. Conclusion: These results indicate that MSCs could serve as an additional extrahepatic virus reservoir, which may play a role at least in part in mediating HBV trans‐infection into the injured tissues through the process of MSCs recruitment.
Clinical significance of precore and core promoter mutations in genotype D hepatitis B‐related chronic liver disease
Authors: Poustchi H. , Mohamadkhani A. , Bowden S. , Montazeri G. , Ayres A. , Revill P. , Farrell G. C. , Locarnini S. , George J. , Malekzadeh R.
Published: May 2008

Summary.  The impact of mutations in the precore and basal core promoter (BCP) regions of the hepatitis B virus on the course of chronic liver disease is not well established. We sought to examine the relationship of these characteristics to the clinical expression of liver disease in patients infected with genotype D chronic hepatitis B (CHB). BCP and precore mutations in 110 patients with genotype D1 CHB were determined and correlated with clinical phenotype. Of 110 patients, 95 (86.5%) were HBeAg‐negative. Compared with HBeAg‐positive subjects, HBeAg‐negative patients were over a decade older and had lower viral loads (3.70 ± 0.98 vs 5.77 ± 0.69 log copies/ml, P < 0.001). The double mutation A1762T‐G1764A was more prevalent in patients with advanced liver disease (AdLD) and was associated with higher alanine aminotransferase and viral load. After adjusting for age, there was a more than fourfold increase in the risk of AdLD with this mutation (OR = 4.4; 95% CI: 1.13–16.92, P < 0.03). Conversely, the G1757A substitution was associated with protection, being 90% less frequent among patients with AdLD (P = 0.001). The results indicate that in genotype D CHB, the presence of the A1762T‐G1764A mutation was associated with more aggressive liver disease while the G1757A substitution was associated with protection from advanced disease.
Lower‐than‐standard dose peg‐IFN alfa‐2a for chronic hepatitis C caused by genotype 2 and 3 is sufficient when given in combination with weight‐based ribavirin
Authors: Weiland O. , Hollander A. , Mattsson L. , Glaumann H. , Lindahl K. , Schvarcz R. , Lindh G. , Enquist R. , Quist A.
Published: May 2008

Summary.  Mono‐therapy with pegylated interferon (peg‐IFN) has shown that a lower‐than‐standard dose yields the same sustained viral response (SVR) rates as standard doses for chronic hepatitis C virus (HCV) infection caused by genotypes 2 or 3. Our aim was to see if a fixed, lower‐than‐standard dose of peg‐IFN alfa‐2a (135 μg weekly) in combination with ribavirin 11 mg/kg daily for 24 weeks yields sufficient SVR rates for genotypes 2 or 3. Hundred consecutive patients with a mean age of 44 years (range 20–69 years), 59 with genotype 3 and 41 with genotype 2, were studied. Rapid viral response (RVR) with HCV‐RNA <15 IU/mL at treatment week 4 and SVR were calculated. RVR was achieved by 28/40 (70%) patients with genotype 2 and 41/58 (71%) with genotype 3. Significantly more genotype 2 patients with RVR achieved SVR 27/28 (96%) than genotype 2 patients who failed to achieve RVR, 8/12 (66%), P = 0.009. The corresponding figures for genotype 3 patients were 39/41 (95%) vs 11/17 (65%), respectively, P = 0.002. In total, SVR was achieved by 35/41 (85%) patients with genotype 2 and 51/59 (86%) patients with genotype 3, respectively. We found that 135 μg peg‐IFN alfa‐2a weekly was sufficient for treatment of genotype 2 and 3 chronic hepatitis C when combined with RBV dosed daily according to body weight. This combination yielded high SVR rates (85–86%) and may be cost‐saving.
Could the depression of obese patients suffering from chronic hepatitis C be temporarily improved?
Authors: Tarantino G. , Basile V. , Conca P. , Ariello M. , Minno M. N. D. Di , Romano A. , Gentile A. , Capone D.
Published: May 2008

Summary.  Depression is an usual finding in patients suffering from chronic hepatitis C. Development of moderate to severe depressive symptoms occurs frequently during pegylated interferon/ribavirin treatment and is generally predicted by baseline depression scores. Furthermore, the obese patients have been found to be twice as likely to suffer from anxiety, impaired social interaction, and depression when compared with the no obese population. In order to evaluate the efficacy of a pharmacological treatment of depression, 68 obese patients with chronic hepatitis C, under or not antiviral therapy, were selected and enrolled into this open, controlled pilot study. Our population was divided in two groups: ‘on Selective Serotonin Reuptake Inhibitors plus support’, with individual titration of medication to adequate side‐effects, including thirty seven patients, and ‘on only support’, involving thirty one patients. Both groups were well balanced for gender, age and antiviral treatment. The selected patients had, at entry, a Beck Depression Inventory score of 24.5 ± 8.1 (mean ± SD). Therapeutic successful outcomes (a decreased score of ≥ 10 units compared to the baseline) were statistically more frequent in antidepressant drug‐treated group (P = 0.005); they were well predicted by dose of Selective Serotonin Reuptake Inhibitors. Thirty five percent of patients were non‐responder to Selective Serotonin Reuptake Inhibitors. The drug tolerability was good. Nearly twenty percent of patients were responder to only support.
The inverse relationship between chronic HBV and HCV infections among injection drug users is associated with decades of age and drug use
Authors: Tseng F.‐C. , Edlin B. R. , Zhang M. , Kral A. , Busch M. P. , Ortiz‐Conde B. A. , Welzel T. M. , O’Brien T. R.
Published: May 2008

Summary.  Infection with hepatitis C virus (HCV) may suppress co‐infection with hepatitis B virus (HBV) during acute or chronic HBV infection. We examined relationships between HBV infection, HCV infection and other factors among injection drug users (IDUs) with antibodies to both viruses. Participants enrolled in a cross‐sectional study during 1998–2000 were considered to have been infected with HBV if they had core antibody, to be chronically infected if they had hepatitis B surface antigen (HBsAg), to have been infected with HCV if they had HCV antibody and to be chronically infected if they had HCV RNA. Among 1694 participants with antibody to both viruses, HBsAg prevalence decreased with increasing age among those positive for HCV RNA [from 4.55% in those 18–29 years to 1.03% in those ≥50 years old (Ptrend = 0.02)], but not among those who were negative for HCV RNA. Chronic HBV infection was less common overall among those with chronic HCV infection (odds ratio [OR], 0.25; P < 0.0001), but this inverse relationship was much stronger in the oldest (>50 years; OR = 0.15) than the youngest (18–29 years; OR = 0.81) participants (Ptrend = 0.03). Similar results were obtained when duration of injection drug use was substituted for age (Ptrend = 0.05). Among IDUs who have acquired both HBV and HCV, chronic HBV infection is much less common among those with chronic HCV infection, but this inverse relationship increases markedly with increasing years of age and injection drug use. Co‐infection with HCV may enhance the resolution of HBsAg during the chronic phases of these infections.
Molecular evolution and population genetics of two Drosophila mettleri cytochrome P450 genes involved in host plant utilization
Authors: BONO JEREMY M. , MATZKIN LUCIANO M. , CASTREZANA SERGIO , MARKOW THERESE A.
Published: May 2008

Understanding the genetic basis of adaptation is one of the primary goals of evolutionary biology. The evolution of xenobiotic resistance in insects has proven to be an especially suitable arena for studying the genetics of adaptation, and resistant phenotypes are known to result from both coding and regulatory changes. In this study, we examine the evolutionary history and population genetics of two Drosophila mettleri cytochrome P450 genes that are putatively involved in the detoxification of alkaloids present in two of its cactus hosts: saguaro (Carnegiea gigantea) and senita (Lophocereus schottii). Previous studies demonstrated that Cyp28A1 was highly up‐regulated following exposure to rotting senita tissue while Cyp4D10 was highly up‐regulated following exposure to rotting saguaro tissue. Here, we show that a subset of sites in Cyp28A1 experienced adaptive evolution specifically in the D. mettleri lineage. Moreover, neutrality tests in several populations were also consistent with a history of selection on Cyp28A1. In contrast, we did not find evidence for positive selection on Cyp4D10, although this certainly does not preclude its involvement in host plant use. A surprising result that emerged from our population genetic analyses was the presence of significant genetic differentiation between flies collected from different host plant species (saguaro and senita) at Organ Pipe National Monument, Arizona, USA. This preliminary evidence suggests that D. mettleri may have evolved into distinctive host races that specialize on different hosts, a possibility that warrants further investigation.
The Importance of ‘Mechnikov’s Thorn’ for an Improved Understanding of 21st Century Medicine and Immunology: A View from the Eye
Authors: McGonagle D. , Georgouli T.
Published: May 2008

In 1908, Ehrlich and Mechnikov shared the Nobel Prize in Medicine for their independent studies that set the scene for the modern understanding of innate and adaptive immunity. However, 20th century immunology thinking was dominated by aberrant adaptive immunity but this never adequately explained the full spectrum of inflammatory disease. This article draws on medical observations, from where immunology originated, and uses the example of the eye to illustrate how the integration of medicine and immunology leads to an improved understanding of inflammation against self. The spectrum of ocular inflammation can be viewed as either predominantly adaptive immune mediated (mostly the realm of immunology), or predominantly due to ocular tissues factors that lead to regional innate immune activation (the realm of medicine), or a variable interaction between the two. Just as the thorns that Mechnikov inserted into molluscs lead to localized innate immune activation; ocular inflammation can likewise be driven by non‐immune factors that include tissue degeneration or microdamage. The present article emphasizes the importance of such factors in the initiation or phenotypic expression of ocular immunopathology allowing different immunological dogmas including self–non‐self discrimination, immunological tolerance and immunoprivilege to be viewed in a different light. This scheme also leads to an appreciation of how the innate immune system may be the sole perpetuator of some ocular immunopathologies. We propose that this integrated view of medicine and immunology is crucial for understanding immunology from a translational angle and has implications far beyond ocular disease.
Association of early growth response‐1 gene polymorphisms with total IgE and atopy in asthmatic children
Authors: Chan Iris H. S. , Tang Nelson L. S. , Leung Ting F. , Huang W. , Lam Yvonne Y. O. , Wong Gary W. K. , Chan Juliana C. N. , Chan Michael H. M. , Wong Chun K. , Zhang Ya P. , Lam Christopher W. K.
Published: May 2008

Early growth response‐1 (Egr‐1) is expressed in human airways and found to modulate tumor necrosis factor, immunoglobulin E (IgE), airway responsiveness, and interleukin‐13‐induced inflammation in mice. We investigated the effects of Chinese‐tagging single nucleotide polymorphisms (SNPs) of Egr‐1 on asthma traits in 298 Chinese asthmatic children and 175 controls, and a replication community cohort of 191 controls. Tag SNP (−4071 A→G) and three additional SNPs (−1427 C→T, −151 C→T and IVS1 −42 C→T) were genotyped by restriction fragment length polymorphism (RFLP). Significant associations were found between plasma total IgE concentration and −4071 A→G (p = 0.008) and IVS1 −42 C→T (p = 0.027) in asthmatic patients. After Bonferroni correction, only −4071 A→G showed significant association. Multivariate regression analysis confirmed this significant association with a standardized coefficient β of 0.156 (95% CI: 0.046–0.317; p = 0.009) in asthmatics among the three SNPs with age and gender‐adjusted. In −4071 A→G, IgElog was significantly higher in patients with the GG genotype than the AA genotype (p = 0.009). In addition, −4071 A→G was significantly associated with atopy (p = 0.016) and high total IgE concentration (p = 0.030) among asthmatics. Patients with the G allele had a 3.5‐fold risk of having atopy and a 2.0‐fold risk of having high total IgE concentration than those homozygous for the A allele. This is the first report to show significant association of Egr‐1 polymorphisms with plasma total IgE and atopy in asthmatics. It may help to explore the pharmacogenetics of Egr‐1 inhibitors.
Transient complete atrioventricular block during liver transplantation
Authors: Nisli Kemal , Oner Naci , Yaren Aysen , Acarli Koray , Gökce Selim , Omeroglu Rukiye , Suoglu Ozlem
Published: June 2008

Abstract:  Intraoperative dysrhythmias commonly occur in the surgical management of congenital heart diseases. It may also be seen in other surgical procedures. The initiating factors for an arrhythmia during surgery is usually a transient insult such as hypoxemia, cardiac ischemia, catecholamine excess, electrolyte abnormality and acidosis. CAVB is a life‐threatening dysrhythmia in all ages. We herein report a case of transient CAVB in a 30‐month‐old boy during living‐related liver transplantation for bile duct paucity‐associated liver cirrhosis. Moreover, we discuss the probable etiology and treatment of CAVB in liver transplantation.
Iron overload in survivors of childhood leukemia after allogeneic hematopoietic stem cell transplantation
Authors: Chotsampancharoen Thirachit , Gan Kwan , Kasow Kimberly A. , Barfield Raymond C. , Hale Gregory A. , Leung Wing
Published: June 2008

Abstract:  Iron overload has not been studied extensively and prospectively in pediatric survivors of allogeneic hematopoietic stem cell transplantation (HSCT); therefore, we conducted a prospective long‐term study of 133 survivors of childhood leukemia to assess the incidence of and risk factors for iron overload and to investigate its association with organ dysfunction. One yr after HSCT, the mean serum ferritin level was 1158 ng/mL (range, 22–3264 ng/mL), with 124 patients (93.2%) having a serum ferritin level that exceeded the upper limit of the normal range (110 ng/mL). Thereafter, the serum ferritin level declined over time. There was a positive correlation between the level of serum ferritin and that of total bilirubin (r = 0.21, p < 0.001) and glutamate pyruvate transaminase (r = 0.17, p < 0.001). A high concentration of serum ferritin was associated with low cardiac fractional shortening (r = −0.15, p = 0.047). In addition, patients with hypothyroidism and GH deficiency had a higher level of serum ferritin than those without (p < 0.02). We conclude that iron overload is common after HSCT and is associated with hepatic, cardiac, and endocrine dysfunction.
Histological and immunohistochemical studies on flower induction in the olive tree (Olea europaea L.)
Authors: Andreini L. , Bartolini S. , Guivarc’h A. , Chriqui D. , Vitagliano C.
Published: June 2008

The aim of this research was to study flower bud differentiation processes in two oil olive cultivars from Tuscan germplasm (Leccino and Puntino). The effect of fruit‐set was studied using ‘ON’ (with fruits) and ‘OFF’ (without fruits) shoots. Axillary buds were periodically collected at different phenological stages, from endocarp sclerification (July) until budbreak in the following spring. Thin sections were analysed using histology (apex size), histochemistry (RNA, starch and soluble carbohydrates) and cytokinin immunocytochemistry (zeatin localisation). The micromorphological observations and histochemical procedures did not allow us to distinguish axillary buds sampled from ‘ON’ and ‘OFF’ shoots. Cytokinin immunocytochemistry revealed early different localisation patterns between ‘ON’ and ‘OFF’ samples. Zeatin accumulated only in ‘OFF’ axillary bud meristems, particularly in July, when endocarp sclerification of fruits from the previous flowering is taking place. At this time, a strong RNA signal was also observed. Both these signals were correlated with floral evocation, and their coincidence with a phenologic stage of development provided a useful tool to determine the time when axillary buds switch from the vegetative to the reproductive phase.
Spring Usurpation Restlessness: A Wasp Social Parasite Adapts its Seasonal Activity to the Host Cycle
Authors: Ortolani Irene , Turillazzi Stefano , Cervo Rita
Published: June 2008

In animals, restlessness is a strategy to fulfil a goal within a narrow seasonal window when ecological and physiological constraints require the performance of certain fundamental events. Although restlessness can be expected in parasitic species that have their biological cycle similar to that of the host, no ‘urge to parasitize’ has thus far been demonstrated in any host‐parasite pair. The paper wasp,Polistes sulcifer, is a social parasite that has lost the nest‐building ability and marked by the absence of the worker caste; it depends on a congeneric host species to reproduce. Host colony usurpation is successful when it occurs in a well‐defined seasonal window. The short time available for host‐nest usurpation might lead to parasite restlessness that overlaps this period. Under controlled laboratory conditions, we demonstrated that the parasite females exhibit ‘usurpation restlessness’ during the period in which field usurpations occur. Additional experiments showed that both this period and laboratory temperature influence the parasite’s ‘urge to usurp’.