bluuebunny/crossref_metadata_2025 huggingface dataset:
Confocal microscopy study of the distribution, content and activity of mitochondria during Paracentrotus lividus development
Authors: MORICI GIOVANNI , AGNELLO MARIA , SPAGNOLO FILIPPO , ROCCHERI MARIA CARMELA , LIEGRO CARLO MARIA DI , RINALDI ANNA MARIA
Published: October 2007

In the present paper we applied confocal microscopy and fluorescence technologies for studying the distribution and the oxidative activity of sea urchin (Paracentrotus lividus) mitochondria during development, by in vivo incubating eggs and embryos with cell‐permeant MitoTracker probes. We calculated, by a mathematical model, the intensity values, the variations of intensity, and the variation index of incorporated fluorochromes. Data demonstrate that mitochondrial mass does not change during development, whereas mitochondrial respiration increases. In addition, starting from 16 blastomeres stage, some regions of the embryo contain organelles more active in oxygen consumption.
Disposition and oral bioavailability of amoxicillin and clavulanic acid in pigs
Authors: REYNS T. , DE BOEVER S. , BAERT K. , CROUBELS S. , SCHAUVLIEGE S. , GASTHUYS F. , DE BACKER P.
Published: October 2007

The pharmacokinetic properties of amoxicillin and clavulanic acid were studied in healthy, fasted pigs after single intravenous (i.v.) and oral (p.o.) dosage of 20 mg/kg of amoxicillin and 5 mg/kg of clavulanic acid. The plasma concentrations of the drugs were determined by validated high‐performance liquid chromatographic methods and the pharmacokinetic parameters were calculated by compartmental and noncompartmental analyses. After i.v. administration of the two drugs, plasma concentration–time curves were best described by a three‐compartmental open model for amoxicillin and a two‐compartmental open model for clavulanic acid. Amoxicillin (with a t1/2γ = 1.03 h and a clearance of 0.58 L/h·kg) and clavulanic acid (with a t1/2β of 0.74 h and a clearance of 0.41 L/h·kg) were both rapidly eliminated from plasma. Both drugs had apparently the same volume of distribution of 0.34 L/kg. After p.o. administration of the two drugs, a noncompartmental model was used. Elimination half‐lives of amoxicillin and clavulanic acid were not significantly different, i.e. 0.73 and 0.67 h respectively. The mean maximal plasma concentrations of amoxicillin and clavulanic acid were 3.14 and 2.42 mg/L, and these were reached after 1.19 and 0.88 h respectively. The mean p.o. bioavailability was found to be 22.8% for amoxicillin and 44.7% for clavulanic acid.
Comparison of plasma histamine levels after intravenous administration of hydromorphone and morphine in dogs
Authors: GUEDES A. G. P. , PAPICH M. G. , RUDE E. P. , RIDER M. A.
Published: October 2007

This study compared plasma histamine concentrations, behavioral and cardiovascular parameters following intravenous administration of hydromorphone and morphine in conscious dogs. Five adult female dogs received a 15‐sec bolus injection of saline, hydromorphone (0.1 and 0.2 mg/kg) or morphine (0.5 and 1.0 mg/kg) randomly at weekly intervals. Blood samples were collected from the jugular vein before and at 1, 2, 5, 15, 30, 60 and 120 min after drug administration. Plasma histamine concentration, noninvasive oscillometric blood pressure, heart rate and rhythm were evaluated. Data were analyzed with repeated measures anova and Tukey–Kramer post hoc test with a 5% significance level. Median plasma histamine increased significantly only after the higher dose of morphine. Maximum plasma histamine measured was 0.8 ng/mL after saline and, after the lower and higher doses, respectively, 10.2 and 9.7 ng/mL for hydromorphone, and 440 and 589 ng/mL for morphine. One dog became hypotensive immediately after receiving the highest dose of morphine. Occasional ventricular premature contractions occurred in one dog after both opioids and dosages. No dogs vomited or defecated, but all salivated profusely with both opioids. Neuroexcitation occurred in four dogs following each opioid. In conclusion, intravenous hydromorphone induced minimal histamine release and was well tolerated by these conscious healthy dogs.
Pharmacokinetics and tissue distribution of enrofloxacin and its active metabolite ciprofloxacin in calves
Authors: DAVIS J. L. , FOSTER D. M. , PAPICH M. G.
Published: October 2007

The purpose of this study was to establish the pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin in the plasma and interstitial fluid (ISF) following subcutaneous (s.c.) administration of enrofloxacin. Ultrafiltration probes were placed in the s.c. tissue, gluteal musculature, and pleural space of five calves. Each calf received 12.5 mg/kg of enrofloxacin. Plasma and ISF samples were collected for 48 h after drug administration and analyzed by high pressure liquid chromatography. Plasma protein binding of enrofloxacin and ciprofloxacin was measured using a microcentrifugation system. Tissue probes were well tolerated and reliably produced fluid from each site. The mean ± SD plasma half‐life was 6.8 ± 1.2 and 7.3 ± 1 h for enrofloxacin and ciprofloxacin, respectively. The combined (ciprofloxacin + enrofloxacin) peak plasma concentration (Cmax) was 1.52 μg/mL, and the combined area under the curve (AUC) was 25.33 μg/mL. The plasma free drug concentrations were 54% and 81% for enrofloxacin and ciprofloxacin, respectively, and free drug concentration in the tissue fluid was higher than in plasma. We concluded that Cmax/MIC and AUC/MIC ratios for free drug concentrations in plasma and ISF would meet suggested ratios for a targeted MIC of 0.06 μg/mL.
Do escaped transgenes persist in nature? The case of an herbicide resistance transgene in a weedy Brassica rapa population
Authors: WARWICK S. I. , LÉGÈRE A. , SIMARD M.‐J. , JAMES T.
Published: October 2007

The existence of transgenic hybrids resulting from transgene escape from genetically modified (GM) crops to wild or weedy relatives is well documented but the fate of the transgene over time in recipient wild species populations is still relatively unknown. This is the first report of the persistence and apparent introgression, i.e. stable incorporation of genes from one differentiated gene pool into another, of an herbicide resistance transgene from Brassica napus into the gene pool of its weedy relative, Brassica rapa, monitored under natural commercial field conditions. Hybridization between glyphosate‐resistant [herbicide resistance (HR)]B. napus and B. rapa was first observed at two Québec sites, Ste Agathe and St Henri, in 2001. B. rapa populations at these two locations were monitored in 2002, 2003 and 2005 for the presence of hybrids and transgene persistence. Hybrid numbers decreased over the 3‐year period, from 85 out of ~200 plants surveyed in 2002 to only five out of 200 plants in 2005 (St Henri site). Most hybrids had the HR trait, reduced male fertility, intermediate genome structure, and presence of both species‐specific amplified fragment length polymorphism markers. Both F1 and backcross hybrid generations were detected. One introgressed individual, i.e. with the HR trait and diploid ploidy level of B. rapa, was observed in 2005. The latter had reduced pollen viability but produced ~480 seeds. Forty‐eight of the 50 progeny grown from this plant were diploid with high pollen viability and 22 had the transgene (1:1 segregation). These observations confirm the persistence of the HR trait over time. Persistence occurred over a 6‐year period, in the absence of herbicide selection pressure (with the exception of possible exposure to glyphosate in 2002), and in spite of the fitness cost associated with hybridization.
Old mice, young islands and competing biogeographical hypotheses
Authors: VAN ZANT JEFFREY L. , WOOTEN MICHAEL C.
Published: October 2007

Naturally occurring variation within a small rodent species native to the southeastern USA, Peromyscus polionotus, has interested biologists for nearly a century. This species has contributed significantly to our understanding of geographical variation and has often been presented as an example of adaptive evolution. Much of the interest in this organism has been predicated on assumptions that the species is relatively young (< 300 000 bp) and that coastal populations have a very recent history (< 10 000 bp). To test these assumptions and the prevailing biogeographical hypothesis (Recurrent Invasion), we examined nucleotide sequence data from the cytochrome b and D‐loop mitochondrial regions (2449 bp) for 79 samples of P. polionotus collected across the Gulf Coast region of Florida and Alabama. Samples representing Peromyscus maniculatus bairdii, P. m. sonoriensis, P. m. pallescens, and P. keeni were used as outgroups. The degree of cytochrome b divergence (≈ 4.4%) between P. maniculatus and P. polionotus was higher than expected. Analyses consistently indicated that three distinct groups are represented within P. polionotus from the Gulf Coast region. Among these, coastal populations (beach mice) form a monophyletic group and apparently represent a substantially older group (≈ 200 000 year. separation) than previously recognized. Our results were counter to the core assumptions of the existing biogeographical model but were consistent with an alternative hypothesis (Shore‐line Tracking) which provides a more parsimonious explanation for the observed patterns. This research provides new insight into the evolutionary history of P. polionotus and highlights the importance of considering biogeographical history when evaluating extant patterns of natural variation.
Density‐related changes in selection pattern for major histocompatibility complex genes in fluctuating populations of voles
Authors: BRYJA J. , CHARBONNEL N. , BERTHIER K. , GALAN M. , COSSON J. ‐F.
Published: October 2007

Host–pathogen interactions are of particular interest in studies of the interplay between population dynamics and natural selection. The major histocompatibility complex (MHC) genes of demographically fluctuating species are highly suitable markers for such studies, because they are involved in initiating the immune response against pathogens and display a high level of adaptive genetic variation. We investigated whether two MHC class II genes (DQA1,DRB) were subjected to contemporary selection during increases in the density of fossorial water vole (Arvicola terrestris) populations, by comparing the neutral genetic structure of seven populations with that estimated from MHC genes. Tests for heterozygosity excess indicated thatDQA1was subject to intense balancing selection. No such selection operated on neutral markers. This pattern of selection became more marked with increasing abundance. In the low‐abundance phase, when populations were geographically isolated, both overall differentiation and isolation‐by‐distance were more marked for MHC genes than for neutral markers. Model‐based simulations identifiedDQA1as an outlier (i.e. under selection) in a single population, suggesting the action of local selection in fragmented populations. The differences between MHC and neutral markers gradually disappeared with increasing effective migration between sites. In the high‐abundance year,DQA1displayed significantly lower levels of overall differentiation than the neutral markers. This gene therefore displayed stronger homogenization than observed under drift and migration alone. The observed signs of selection were much weaker forDRB. Spatial and temporal fluctuations in parasite pressure and locus‐specific selection are probably the most plausible mechanisms underlying the observed changes in selection pattern during the demographic cycle.
Identification of differentially expressed small non‐coding RNAs in the legume endosymbiont Sinorhizobium meliloti by comparative genomics
Authors: Del Val Coral , Rivas Elena , Torres‐Quesada Omar , Toro Nicolás , Jiménez‐Zurdo José I.
Published: October 2007

Bacterial small non‐coding RNAs (sRNAs) are being recognized as novel widespread regulators of gene expression in response to environmental signals. Here, we present the first search for sRNA‐encoding genes in the nitrogen‐fixing endosymbiont Sinorhizobium meliloti, performed by a genome‐wide computational analysis of its intergenic regions. Comparative sequence data from eight related α‐proteobacteria were obtained, and the interspecies pairwise alignments were scored with the programs eQRNA and RNAz as complementary predictive tools to identify conserved and stable secondary structures corresponding to putative non‐coding RNAs. Northern experiments confirmed that eight of the predicted loci, selected among the original 32 candidates as most probable sRNA genes, expressed small transcripts. This result supports the combined use of eQRNA and RNAz as a robust strategy to identify novel sRNAs in bacteria. Furthermore, seven of the transcripts accumulated differentially in free‐living and symbiotic conditions. Experimental mapping of the 5′‐ends of the detected transcripts revealed that their encoding genes are organized in autonomous transcription units with recognizable promoter and, in most cases, termination signatures. These findings suggest novel regulatory functions for sRNAs related to the interactions of α‐proteobacteria with their eukaryotic hosts.
Parkinson's disease: a dual‐hit hypothesis
Authors: Hawkes C. H. , Del Tredici K. , Braak H.
Published: October 2007

Accumulating evidence suggests that sporadic Parkinson's disease has a long prodromal period during which several non‐motor features develop, in particular, impairment of olfaction, vagal dysfunction and sleep disorder. Early sites of Lewy pathology are the olfactory bulb and enteric plexus of the stomach. We propose that a neurotropic pathogen, probably viral, enters the brain via two routes: (i) nasal, with anterograde progression into the temporal lobe; and (ii) gastric, secondary to swallowing of nasal secretions in saliva. These secretions might contain a neurotropic pathogen that, after penetration of the epithelial lining, could enter axons of the Meissner's plexus and, via transsynaptic transmission, reach the preganglionic parasympathetic motor neurones of the vagus nerve. This would allow retrograde transport into the medulla and, from here, into the pons and midbrain until the substantia nigra is reached and typical aspects of disease commence. Evidence for this theory from the perspective of olfactory and autonomic dysfunction is reviewed, and the possible routes of pathogenic invasion are considered. It is concluded that the most parsimonious explanation for the initial events of sporadic Parkinson's disease is pathogenic access to the brain through the stomach and nose – hence the term ‘dual‐hit’.
Sequential myelin protein expression during remyelination reveals fast and efficient repair after central nervous system demyelination
Authors: Lindner M. , Heine S. , Haastert K. , Garde N. , Fokuhl J. , Linsmeier F. , Grothe C. , Baumgärtner W. , Stangel M.
Published: October 2007

To understand the mechanisms of remyelination and the reasons for regeneration failure is one of the major challenges in multiple sclerosis research. This requires a good knowledge and reliable analysis of experimental models. This work was undertaken to characterize the pattern of myelin protein expression during experimental remyelination. Acute demyelination of the corpus callosum was induced by feeding of 0.3% cuprizone for 6 weeks, followed by a 10‐week remyelination period. We used a combination of Luxol fast blue (LFB) myelin staining, electron microscopy (EM) and immunohistochemistry for the myelin proteins 2′,3′‐cyclic nucleotide 3′ phosphodiesterase (CNPase), myelin basic protein (MBP), proteolipid protein (PLP) and myelin oligodendrocyte glycoprotein (MOG). Early remyelination was detected by the re‐expression of CNPase, MBP and PLP as early as 4 days. MOG, as a marker for late differentiation of oligodendrocytes, was not detectable until 2 weeks of remyelination. EM data correlated well with the LFB myelin staining and myelin protein expression, with 50% of the axons being rapidly remyelinated within 2 weeks. While particularly MBP but also PLP and CNPase are re‐expressed very early before significant remyelination is observed by EM, the late marker MOG shows a lag behind the remyelination detected by EM. The presented data indicate that immunohistochemistry for various myelin proteins expressed early and late during myelin formation is a suitable and reliable method to follow remyelination in the cuprizone model. Furthermore, investigation of early remyelination confirms that the intrinsic repair programme is very fast and switched on within days.
Use of p62/SQSTM1 antibodies for neuropathological diagnosis
Authors: Kuusisto E. , Kauppinen T. , Alafuzoff I.
Published: October 2007

The demonstration of proteinaceous inclusions in the brain is the key step in the pathological diagnosis of degenerative dementias. The diversity of these diseases has necessitated the use of a panel of (immuno)stains to visualize all suspect pathologies, elevating diagnostic costs. Immunodetection of p62 (sequestosome 1), an abundant constituent in diverse pathological inclusions, holds the potential for a broad‐specificity, high‐contrast inclusion label. In the brain, pathological p62‐positive aggregates comprise both cytoplasmic and nuclear types in neurones and glia, with abnormal tau, alpha‐synuclein, TAR DNA‐binding protein 43 or polyglutamine proteins as primary components. We therefore set out to evaluate the performance of p62 antibodies for diagnostic immunohistochemistry. We optimized the application conditions and compared the staining profiles of eight commercial p62 antibodies with each other and with reference immunostains, using 2‐mm tissue multiarrays representing the major tauo‐ and synucleinopathies and frontotemporal lobar degeneration with ubiquitin‐positive inclusions (FTLD‐U). The lesions were best visualized using monoclonal antibodies, displaying most types of hallmark inclusions with excellent contrast. Expanding the list of p62‐containing aggregates, we demonstrated p62 in tufted astrocytes, coiled bodies, astrocytic plaques, and variform neocortical inclusions and pathological processes in FTLD‐U. Polyclonal antibodies exhibited lower sensitivities with variable background levels. We also noted more subtle p62‐immunoreactive features lacking overt disease associations. Emphasizing the importance of proper antibody and epitope unmasking methods for maximum sensitivity, we recommend p62 immunodetection as a screening stain for diagnostic practice.
Larval morphology enhances phylogenetic reconstruction in Cetoniidae (Coleoptera: Scarabaeoidea) and allows the interpretation of the evolution of larval feeding habits
Authors: MICÓ ESTEFANIA , MORÓN MIGUEL ÁNGEL , ŠÍPEK PETR , GALANTE EDUARDO
Published: October 2007

Abstract The Cetoniidae, the showiest of scarabs, comprises some 3900 species in 515 genera, distributed worldwide except for subpolar areas and some offshore New Zealand islands. Parsimony analysis of 76 larval and adult characters and 42 terminal taxa supports the monophyly of Cetoniidae (sensu Krikken, 1984), but not of the traditionally considered subfamilies Cetoniinae and Trichiinae (sensu Krikken, 1984). In the study taxon, larval characters are shown to be more informative than those of adults for deeper phylogeny. The evolution of some larval characters (head and legs) in relation to feeding habits is discussed on the basis of phylogenetic analysis. The results show an evolutionary shift from wood associations to a higher ecological plasticity that allows the larvae to feed on wide sources of organic matter (including compost, dung, gopher burrows, packrat middens, ant debris piles, etc.).
Over‐expression of the Arabidopsis AtMYB41 gene alters cell expansion and leaf surface permeability
Authors: Cominelli Eleonora , Sala Tea , Calvi Daniele , Gusmaroli Giuliana , Tonelli Chiara
Published: October 2007

The Arabidopsis AtMYB41 gene encodes an R2R3‐MYB transcription factor whose expression is not detectable under normal growth conditions in any organ or at any developmental stage analysed. It is expressed at high levels in response to drought, ABA and salt treatments, suggesting a possible role in stress responses. Transgenic lines over‐expressing this transcription factor showed a pleiotropic phenotype similar to that exhibited by some mutants that affect cuticle biosynthesis. This includes a dwarf appearance, dependent on smaller cells with abnormal morphology, enhanced sensitivity to desiccation, and enhanced permeability of leaf surfaces, suggesting discontinuity in the cuticle. The expression of genes involved in lipid metabolism and transport, in cell‐wall modifications and cell expansion, genes coding for membrane‐associated proteins and genes specifically involved in cuticle metabolism was differentially modulated between wild‐type and transgenic plants, suggesting a direct or indirect role of AtMYB41 in the regulation of their transcription. Taken together, our results suggest that AtMYB41 is part of a complex network of transcription factors controlling cell expansion and cuticle deposition in response to abiotic stress.
The GRV2/RME‐8 protein of Arabidopsis functions in the late endocytic pathway and is required for vacuolar membrane flow
Authors: Silady Rebecca A. , Ehrhardt David W. , Jackson Karen , Faulkner Christine , Oparka Karl , Somerville Chris R.
Published: October 2007

The gravitropism defective 2 (grv2) mutants of Arabidopsis thaliana were previously characterized as exhibiting shoot agravitropism resulting from mutations in a homolog of the Caenorhabditis elegans RECEPTOR‐MEDIATED ENDOCYTOSIS‐8 (RME‐8) gene, which is required in C. elegans for endocytosis. A fluorescent protein fusion to the GRV2 protein localized to endosomes in transgenic plants, and vacuolar morphology was altered in grv2 mutants. A defect in vacuolar membrane dynamics provides a mechanistic explanation for the gravitropic defect, and may also account for the presence of an enlarged vacuole in early embryos, together with a nutrient requirement during seedling establishment. The GRV2‐positive endosomes were sensitive to Wortmannin but not brefeldin A (BFA), consistent with GRV2 operating late in the endocytic pathway, prior to delivery of vesicles to the central vacuole. The specific enlargement of GRV2:YFP structures by Wortmannin, together with biochemical data showing that GRV2 co‐fractionates with pre‐vacuolar markers such as PEP12/SYP21, leads us to conclude that in plants GRV2/RME‐8 functions in vesicle trafficking from the multivesicular body/pre‐vacuolar compartment to the lytic vacuole.
Bleomycin‐induced flagellate dermatitis
Authors: Vuerstaek Jeroen D. D. , Frank Jorge , Poblete‐Gutiérrez Pamela
Published: October 2007

A 62‐year‐old man with testis carcinoma was treated with bleomycin, cisplatin, and etoposide (BEP). During the second cycle of this chemotherapeutic regimen, he developed nonpruritic, linear erythematous lesions in a flagellate‐like fashion on the trunk and extremities. After a short‐term oral prednison therapy and ceasing bleomycin administration, these lesions completely resolved. Herein, the characteristic cutaneous side effects of bleomycin are discussed.
Sporadic nonsyndromal anterior cervical hypertrichosis: case report and review of the literature
Authors: Heitink Martijn V. , Quaedvlieg Patricia J. F. , Van Neer Francoise J. M. A. , Frank Jorge
Published: October 2007

A 13‐year‐old girl presented with cosmetically disturbing excessive hair growth in the anterior cervical region that had been present since birth. An X‐ray of the cervical and lumbosacral spine did not show any ossal changes. Based on the clinical findings, the diagnosis of anterior cervical hypertrichosis was made. We successfully treated the patient with an intense pulsed light source. Here, we briefly discuss and review the clinical presentation and causes of localized and generalized hypertrichosis as well as possible treatment modalities.
Nail pigmentation due to hydroxycarbamide
Authors: Ceulen Roeland P. M. , Frank Jorge , Poblete‐Gutiérrez Pamela
Published: October 2007

A 47‐year‐old male developed both longitudinal melanonychia and periungual hyperpigmentation 6 months after initiation of hydroxycarbamide (synonym: hydroxyurea) therapy for chronic myeloproliferative disease. Based on the clinical symptoms observed in this patient, the broad differential diagnostic spectrum of hyperpigmentation of the nails is briefly reviewed here. In individuals who undergo hydroxycarbamide treatment, melanonychia might sometimes be seen as side effect and always has to be differentiated from subungual malignant melanoma.
Juvenile amyopathic dermatomyositis with concomitant heart disease
Authors: Nellen Ruud G. L. , Rijzewijk Joris J. , Frank Jorge , Poblete‐Gutiérrez Pamela
Published: October 2007

Within the group of inflammatory myopathies, dermatomyositis is the most frequent disease occurring in childhood. Although most children usually present with muscle disease and dermatological symptoms, a small number of these patients does not manifest myopathy at the time of disease onset. They are therefore diagnosed with juvenile amyopathic dermatomyositis. Sometimes, other organs systems can also be affected, such as the lung, gastrointestinal tract, and heart. As to the latter, the occurrence of cardiac symptoms such as arrhythmia or conduction defects are rare. Here, we report for the first time a patient with childhood amyopathic dermatomyositis and concomitant congenital heart anomalies, including coarctation of the aorta.
Erythema nodosum as an early sign of Crohn's disease
Authors: Van Der Velden Jaap J. A. J. , Van Marion Ariënne M. W. , Kremer Bernd , Straetmans Jos M. J. A. A. , Henquet Charles J. M. , Frank Jorge
Published: October 2007

Erythema nodosum is the most common form of septal panniculitis and the most frequent skin manifestation associated with inflammatory bowel disease. Since the development of erythema nodosum is closely related with a variety of disorders and conditions, it can serve as an important early sign of systemic disease. We report on a 25‐year‐old woman with Crohn's disease following a long history of recurrent erythema nodosum.
Lupus erythematosus associated with erythema multiforme: Rowell's syndrome
Authors: Shadid Nadia H. , Thissen Carleine A. C. B. , Van Marion Ariënne M. W. , Poblete‐Gutiérrez Pamela , Frank Jorge
Published: October 2007

About 45 years ago, the association of lupus erythematosus with erythema multiforme and specific immunological laboratory changes was described for the first time. Since then, several patients with similar constellations of clinical symptoms and laboratory parameters have been reported. Today, this disease is known as Rowell's syndrome. However, the fact that not all patients described previously fit all clinical and immunological characteristics that had been originally reported raised the question if Rowell's syndrome really is an own entity or if the simultaneous occurrence of these clinical and immunological signs is rather incidental. Here, we describe a patient fulfilling most of the criteria of Rowell's syndrome and discuss what is currently known about this rare condition.
Bullous congenital ichthyosiform erythroderma of Brocq
Authors: Kucharekova Martina , Mosterd Klara , Winnepenninckx Veronique , Van Geel Michel , Sommer Anja , Van Steensel Maurice A. M.
Published: October 2007

Bullous congenital ichthyosiform erythroderma (BCIE), also known as epidermolytic hyperkeratosis (EHK, OMIM 113800) is characterized by erythroderma and blistering at birth, leading to generalized hyperkeratosis of varying severity in adulthood. Clinically, BCIE can be divided into two groups: BCIE with or without palmoplantar involvement, associated with mutations in keratin 1 or keratin 10, respectively. Here we report a newborn with generalized erythema, blistering and erosions at the time of birth. No hyperkeratosis was seen on the palms and soles. The lack of palmoplantar involvement suggested that keratin 10 could be involved. DNA analysis showed a known mutation in the keratin 10 gene.
Ossification of the auricle
Authors: Sterneberg‐Vos Heleen , Winnepenninckx Veronique , Frank Jorge , Kelleners‐Smeets Nicole W.
Published: October 2007

The auricle is a flexible structure because it is formed by elastic cartilage. In the rare occurrence of ectopic auricular ossification, however, the cartilage is replaced by lamellar bone and becomes petrified. Such unphysiological replacement has been reported in association with local trauma, inflammation, systemic diseases, and hypothermia. Here, we report a patient with unilateral ossification of the auricle secondary to frostbite.
Epidermodysplasia verruciformis: unsuccessful therapeutic approach with imiquimod
Authors: Janssen Kathleen , Lucker Georges P. H. , Houwing Ronald H. , Van Rijssel R.
Published: October 2007

Epidermodysplasia verruciformis (EV) is a rare heritable disease characterized by an unusual susceptibility to infection with specific types of human papillomavirus and a propensity for developing skin malignant tumors. Partial defects in cell‐mediated immunity have been demonstrated in this disease. Here, we describe a patient with EV who was treated unsuccessfully with imiquimod.
Porphyria cutanea tarda in pre‐existent lupus erythematosus – is there an association?
Authors: Van Tuyll van Serooskerken Anne‐Moon , Habets J. M. Werner , Badeloe Sadhanna , Poblete‐Gutiérrez Pamela , Frank Jorge
Published: October 2007

In lupus erythematosus (LE), vesicles and bullae are only rarely seen. However, in some instances such efflorescences might suggest an association with distinct cutaneous diseases, including erythema multiforme, toxic epidermal necrolysis or autoimmune blistering disorders such as bullous pemphigoid, pemphigus vulgaris, and dermatitis herpetiformis Duhring. Another blistering disease that has been described in association with cutaneous and systemic LE is porphyria cutanea tarda (PCT). PCT is a metabolic disorder caused by a deficiency of the fifth enzyme in heme biosynthesis, uroporphyrinogen decarboxylase. Here, we report on a 57‐year‐old Caucasian woman of Dutch origin with a medical history of mild cutaneous LE who developed skin fragility, blistering skin lesions, milia, and facial hypertrichosis. Subsequent porphyrin analysis in urine and feces confirmed the suspected simultaneous manifestation of LE and PCT.
A new HLA‐B*44 variant, B*4453, identified by haplotype‐specific extraction and sequencing‐based typing
Authors: Ulrich S. , Posch U. , Helmberg W. , Lanzer G.
Published: October 2007

We report the identification of a novel HLA B*44 allele, officially named B*4453, found in an Austrian patient and his two sisters.
Haplotype‐specific pattern of association of human major histocompatibility complex with non‐Hodgkin’s lymphoma outcome
Authors: Nowak J. , Kalinka‐Warzocha E. , Juszczyński P. , Mika‐Witkowska R. , Zajko M. , Graczyk‐Pol E. , Coiffier B. , Salles G. , Warzocha K.
Published: October 2007

In the previous studies, some human major histocompatibility complex (MHC) genes such as TNF, LTA and human leukocyte antigen (HLA)‐DR2 genes and A1‐B8‐TNF−308A haplotype were implied in non‐Hodgkin’s lymphoma (NHL) outcome. In the current study, we have assigned most probable six‐locus haplotypes determined by HLA‐A, ‐Cw, ‐B and ‐DRB1 highly polymorphic genes and non‐HLA LTA+252 and TNF−308 single nucleotide polymorphisms (SNPs) in 152 NHL Caucasian French patients. We have broadly mapped the MHC region by its component blocks and tagging alleles. Ten frequent (with haplotype frequency >1%) six‐locus extended haplotypes (EHs) were revealed in NHL patients. The only two adjacent locus fragment of 8.1 EH associated with shortened freedom from progression (FFP) was B*08‐LTA+252G (P= 0.0084, RR = 2.45). Interestingly, 305‐kbp‐long, four‐locus fragment of 8.1 EH, Cw*07‐B*08‐LTA+252G‐TNF−308A block was much strongly associated with shortened FFP (P= 0.00045, RR = 3.26). The analysis of further extended haploblocks comprising five or six loci showed weaker association with outcome measures, suggesting linkage disequilibrium to be the cause of DRB1*03 and A*01 allele associations. In contrast, all fragments of 7.1 EH influenced FFP favorably with top association of TNF−308G allele. In multivariate analysis, only Cw*07‐B*08‐LTA+252G‐TNF−308A and TNF−308G‐DRB1*01 haplotypes remained predictive for shortened FFP (P= 0.024 and 0.027, respectively) and independent of International Prognostic Index (P= 0.00044). This study reveals that the block composition of EHs may cause important functional differences for NHL outcomes. Further study will be required in NHL patients by fine mapping with dense microsatellite or SNP tags to define susceptibility genes in associating regions.
Malignant hepatic tumor occurring 10 yrs after a histocompatible sibling donor bone marrow transplantation for severe aplastic anemia
Authors: Ishimura Masataka , Ohga Shouichi , Nagatoshi Yoshihisa , Okamura Jun , Tajiri Tatsuro , Kohashi Kenichi , Oda Yoshinao , Takada Hidetoshi , Hara Toshiro
Published: October 2007

Abstract:  A 13‐yr‐old boy developed post‐transplant liver tumor. At three yrs of age, this patient underwent a histocompatible sibling donor BMT for severe aplastic anemia, after a conditioning with antithymocyte globulin and cyclophosphamide. He became a HBV carrier after BMT. Stable mixed chimerism and mild thrombocytopenia, but no active hepatitis continued. At age 13, abdominal pain was a sign of massive tumor. Extremely high levels of α‐fetoprotein indicated the clinical diagnosis of hepatoblastoma that might be the first report as post‐BMT malignancy. The necropsy specimens revealed that the tumor was recipient cell‐origin and showed the histopathological features of both hepatoblastoma and hepatocellular carcinoma. Prolonged mixed chimerism and hepatitis virus infection might induce a rare oncogenesis after non‐irradiated conditioning.
Outcome of bowel perforation after pediatric liver transplantation
Authors: Dehghani Seyed Mohsen , Nikeghbalian Saman , Kazemi Koorosh , Dehghani Masood , Gholami Siavash , Bahador Ali , Salahi Heshmatollah , Malek‐Hosseini Seyed Ali
Published: October 2007

Abstract: Bowel perforation is one of the causes of mortality after pediatric liver transplantation. The aim of this study was to evaluate the incidence, risk factors, clinical presentations, and outcomes of bowel perforation in pediatric liver recipients. This is a retrospective analysis of all pediatric patients who underwent liver transplantation at a single liver transplant center in Iran between 1999 and 2006. During this period 72 liver transplantations were performed in children <18 yr. Twenty‐two children underwent 33 re‐explorations after liver transplantation. Five bowel perforations occurred in four children (incidence, 6.9%). One patient required two re‐explorations. The median time between liver transplantation and the diagnosis of the bowel perforation was seven days. All patients had abdominal distention before re‐exploration. The sites of perforation were jejunum (n = 3) and ileum (n = 2), and simple repair was performed in all cases. Three children had a history of prior Kasai operation. One of them received high dose of methylprednisolone before bowel perforation. Two children expired after bowel perforation (mortality rate, 50%). Bowel perforation is relatively frequent after pediatric liver transplantation. Among risk factors, prior Kasai operation may have a role. We observed that abdominal distention is a sign of bowel perforation and a high index of suspicion is required for rapidly diagnosis of this complication. The outcome of bowel perforation is poor and its mortality is high. Further studies are needed to establish real risk factors for this complication.
Prolonged Gestation in Two Holstein Cows: Transabdominal Ultrasonographic Findings in Late Pregnancy and Pathologic Findings in the Fetuses
Authors: Buczinski S. , Bélanger A.‐M. , Fecteau G. , Roy J.‐P.
Published: October 2007

Prolonged pregnancy in cattle is a rare condition that is commonly accompanied with fetal adenohypophyseal hypoplasia. The final diagnosis is often challenging as breeding date error remains possible in virtually all situations. In this report, fetal wellbeing assessment is depicted in two Holstein cows suffered from prolonged pregnancy. Transabdominal ultrasonographic findings were compatible with healthy non‐stressed fetuses. The clinical and pathologic findings encountered in both fetuses expelled after corticosteroid induction of parturition consisted of adenohypophyseal aplasia and hydronephrosis. Other nervous system anomalies (hydrocephaly or holocephaly) were observed. Tetralogy of Fallot was also found in one calf.
Pharmacokinetics and Mammary Residual Depletion of Erythromycin in Healthy Lactating Ewes
Authors: Goudah A. , Sher Shah S. , Shin H.C. , Shim J.H. , Abd El‐Aty A. M.
Published: October 2007

The aim of this investigation was to examine the pharmacokinetics and mammary excretion of erythromycin administered to lactating ewes (n = 6) by the intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) routes at a dosage of 10 mg/kg. Blood and milk samples were collected at pre‐determined times, and a microbiological assay method was used to measure erythromycin concentrations in serum and milk. The concentration–time data were analysed by compartmental and non‐compartmental kinetic methods. The serum concentration–time data of erythromycin were fit to a two‐compartment model after i.v. administration and a one‐compartment model with first‐order absorption after i.m. and s.c. administration. The elimination half‐life (t1/2β) was 4.502 ± 1.487 h after i.v. administration, 4.874 ± 0.296 h after i.m. administration and 6.536 ± 0.151 h after s.c. administration. The clearance value (Cltot) after i.v. dosing was 1.292 ± 0.121 l/h/kg. After i.m. and s.c. administration, observed peak erthyromycin concentrations (Cmax) of 0.918 ± 0.092 μg/ml and 0.787 ± 0.010 μg/ml were achieved at 0.75 and 1.0 h (Tmax) respectively. The bioavailability obtained after i.m. and s.c. administration was 91.178 ± 10.232% and 104.573 ± 9.028% respectively. Erythromycin penetration from blood to milk was quick for all the routes of administration, and the high AUCmilk/AUCserum (1.186, 1.057 and 1.108) and Cmax‐milk/Cmax‐serum ratios reached following i.v., i.m. and s.c. administration, respectively, indicated an extensive penetration of erythromycin into the milk.
Intra‐tumoral Gene Delivery of feIL‐2, feIFN‐γ and feGM‐CSF using Magnetofection as a Neoadjuvant Treatment Option for Feline Fibrosarcomas: A Phase‐I Study
Authors: Jahnke A. , Hirschberger J. , Fischer C. , Brill T. , Köstlin R. , Plank C. , Küchenhoff H. , Krieger S. , Kamenica K. , Schillinger U.
Published: October 2007

Despite aggressive pre‐ or postoperative treatment, feline fibrosarcomas have a high relapse rate. In this study, a new treatment option based on immune stimulation by intra‐tumoral delivery of three feline cytokine genes was performed. The objective of this phase‐I dose‐escalation study was to determine a safe dose for further evaluation in a subsequent phase‐II trial. Twenty‐five client‐owned cats with clinical diagnosis of fibrosarcoma – primary tumours as well as recurrences – entered the study. Four increasing doses of plasmids coding for feIL‐2, feIFN‐γ or feGM‐CSF, respectively, were previously defined. In groups I, II, III and IV these doses were 15, 50, 150 and 450 μg per plasmid and a corresponding amount of magnetic nanoparticles. Two preoperative intra‐tumoral injections of the magnetic DNA solution were followed by magnetofection. A group of four control cats received only surgical treatment. Side effects were registered and graded according to the VCOG‐CTCAE scale and correlated to treatment. Statistical analyses included one‐wayanova,post hocand Kruskal–Wallis tests. ELISA tests detecting plasma feIFN‐γ and plasma feGM‐CSF were performed. One cat out of group IV (450 μg per plasmid) showed adverse events probably related to gene delivery. As these side effects were self‐limiting and occurred only in one of eight cats in group IV, this dose was determined to be well tolerable. Altogether six cats developed local recurrences during a 1‐year observation period. Four of these cats had been treated with dose IV. Regarding these observations, a subsequent phase‐II trial including a representative amount of cats should be tested for the efficacy of dose IV as well as dose III.
Rural and remote health research: Key issues for health providers in southern Queensland
Authors: Eley Rob M. , Baker Peter G.
Published: October 2007

Objective:  To determine what community health service providers in rural southern Queensland considered were major issues affecting their efficacy. Results will inform the future research strategy of the Centre for Rural and Remote Area Health with the aim of addressing specific regional needs.

Design:  Interactive research workshops.

Setting:  Health providers and other key stakeholders.

Subjects:  Participants from organisations directly involved with health care were complemented by representatives from local government, the police service and church groups.

Main outcome measures:  The workshops used the nominal group technique to identify what participants considered were key health issues in their locations. These issues were then prioritised by the participants. Thematic analysis of the issues generated a ranking of themes by importance. Results were compared with a similar exercise undertaken in 2003.

Results:  Seventeen themes were identified, with workforce by far the major concern of health providers. Recruitment and retention of health workers were the principal issues of concern. The other four highest ranked themes across all workshops were mental health care, access to health services, perceptions and expectations of consumers, and interagency cooperation. The workshops provided important information to the Centre for Rural and Remote Area Health for developing research strategy. Additionally, new alliances among health providers were developed which will support sharing of information and resources.

Conclusion:  The workshops enabled organisations to meet and identify the key health issues and supported research planning. New alliances among health providers were forged, and collaborative research avenues are being explored. The workshop forum is an excellent means of information exchange.
Evaluating the effectiveness of a university health sciences experience program for regional Year 10 students
Authors: Penman Joy , Ellis Bronwyn , White Frances , Misan Gary
Published: October 2007

Objective:  The main aim of this pilot program was to raise secondary students' awareness of university studies and careers in the health sciences through a three‐day program. Further aims of the program were to increase the participants' knowledge of health issues through group activities, and provide an opportunity to interact with university staff and health professionals.

Design:  The participants were surveyed at the conclusion of the program using an online questionnaire (30 items) consisting of both open and closed questions.

Setting:  The program and evaluation were carried out at a regional campus of a metropolitan‐based university during the mid‐year vacation.

Participants:  Fourteen Year 10 students (11 female, 3 male; 5 from government schools, 9 from a non‐government school) from a regional city completed the evaluation.

Main outcome measures:  Satisfaction with the program, increased awareness of pathways into university, and changes in attitude about university as a career option.

Results:  The evaluation revealed that the participants had had a pleasant learning experience, which had led them to feel positive about university studies in general and as an option for themselves. They made useful suggestions for improvements.

Conclusion:  The evaluation of the effectiveness of the program showed that it had achieved its objectives. It also provided the program organisers with insights regarding timing and activities, which will be useful in improving future programs targeting secondary students.
The Monaro Grassland Conservation Management Network: Reconnecting the sward
Authors: Eddy David
Published: October 2007

Summary  This article describes the context, evolution and structure of the Monaro Grassland Conservation Management Network, a loose framework of private and public land managers and their grassland properties located in the Monaro region of south‐eastern New South Wales. The Monaro region is characterized by lower rainfall, lower temperatures and less productive soils than other agricultural regions in south‐eastern Australia containing natural temperate grasslands. As such, it offers important opportunities for conservation of natural temperate grasslands as a significant and functional component of the landscape, under a variety of land tenures and uses including pastoral agriculture.
Icons under threat: Why monitoring visitors and their ecological impacts in protected areas matters
Authors: Hadwen Wade L. , Hill Wendy , Pickering Catherine M.
Published: October 2007

Summary  Visitation levels are on the rise in protected areas throughout the world. In response, many icon sites are showing signs of overuse and more protected‐area managers report tourism and recreation as threats to sustainable management. Clearly, there is a growing need to assess (monitor) and manage visitors to mitigate their impacts. In this paper, we articulate why targeted visitor‐impact monitoring matters and highlight how existing monitoring programmes fail to deliver the necessary information to protected‐area managers. We suggest that the availability and quality of visitor data are currently insufficient to facilitate the development of proactive management strategies in most protected areas. We call for more scale‐sensitive (time and space) collection of visitor load and environmental (response) data. Specifically, since icon sites (like waterfalls and mountain peaks) are the focus of visitor motivations and activities, we highlight the case for proactive assessment, management and reporting of condition at these sites. Ultimately, visitor trends will be influenced by visitor management. If visitor activities degrade the icon, the financial benefits of tourism and recreation to a protected area may not be sustainable. In addition, the conservation and protection objectives of the protected area will also not be met.
Developing strategies and methods for rehabilitating degraded pastures using native grasses
Authors: Firn Jennifer
Published: October 2007

Summary  The purpose of this comment paper is to highlight the need for more research that aims to develop strategies and methods for establishing and maintaining native grasses in degraded pastures. Clues to finding the best strategies are linked to the vigorous debate concerning the relationship between biodiversity and ecosystem function, which has resonated in ecological research for more than 20 years. Studies aimed at investigating the operational validity of the ‘sampling effect’ hypothesis vs. the ‘niche complementarity’ hypothesis could provide valuable direction on how to successfully re‐establish healthy and stable native pasture communities, including the number of species and functional groups needed. Once strategies have been developed, then practical methods on grazing management and sowing are also needed. In the long run, research initiatives in this direction could act to benefit the conservation of native grass diversity, while at the same time, sustain important ecological (and economic) functions such as production, nutrient cycling and resistance to invasion.