bluuebunny/crossref_metadata_2025 huggingface dataset:
Diversity and clustered distribution of retrotransposable elements in the compact genome of the pufferfish Tetraodon nigroviridis
Authors: Fischer C. , Bouneau L. , Coutanceau J.-P. , Weissenbach J. , Ozouf-Costaz C. , Volff J.-N.
Published: July 2005

We report the characterization and chromosomal distribution of retroelements in the compact genome of the pufferfish Tetraodon nigroviridis. We have reconstructed partial/complete retroelement sequences, established their phylogenetic relationship to other known eukaryotic retrotransposons, and performed double-color FISH analyses to gain new insights into their patterns of chromosomal distribution. We could identify 43 different reverse transcriptase retrotransposons belonging to the three major known subclasses (14 non-LTR retrotransposons from seven clades, 25 LTR retrotransposons representing the five major known groups, and four Penelope-like elements), and well as two SINEs (non-autonomous retroelements). Such a diversity of retrotransposable elements, which seems to be relatively common in fish but not in mammals, is astonishing in such a compact genome. The total number of retroelements was approximately 3000, roughly representing only 2.6% of the genome of T. nigroviridis. This is much less than in other vertebrate genomes, reflecting the compact nature of the genome of this pufferfish. Major differences in copy number were observed between different clades, indicating differential success in invading and persisting in the genome. Some retroelements displayed evidence of recent activity. Finally, FISH analysis showed that retrotransposable elements preferentially accumulate in specific heterochromatic regions of the genome of T. nigroviridis, revealing a degree of genomic compartmentalization not observed in the human genome.
Phylogenomic analysis of chromoviruses
Authors: Gorinšek B. , Gubenšek F. , Kordiš D.
Published: July 2005

Genome sequences of model organisms provide a unique opportunity to obtain insight into the complete diversity of any transposable element (TE) group. A limited number of chromoviruses, the chromodomain containing genus of Metaviridae, is known from plant, fungal and vertebrate genomes. By searching diverse eukaryotic genome databases, we have found a surprisingly large number of new, structurally intact and highly conserved chromoviral elements, greatly exceeding the number of previously known chromoviruses. In this study, we examined the diversity, origin and evolution of chromoviruses in Eukaryota. Chromoviral diversity in plants, fungi and vertebrates, as shown by phylogenetic analyses, was found to be much greater than previously expected. A novel centromere-specific chromoviral lineage was found to be widespread and highly conserved in all seed plants. The age of chromoviruses has been significantly extended by finding their representatives in the most basal plant lineages (green and red algae), in Heterokonta (oomycetes) and in Cercozoa (plasmodiophorids). The evolutionary origin of chromoviruses has been found to be no earlier than in Cercozoa, since none can be found in the basal eukaryotic lineages, despite the extensive genome data. The evolutionary dynamics of chromoviruses can be explained by a strict vertical transmission in plants and fungi, while in Metazoa it is more complex. The currently available genome data clearly show that chromoviruses are the most widespread and one of the oldest Metaviridae clade.
Abyss1: A novel L2-like non-LTR retroelement of the snakelocks anemone (Anemonia sulcata)
Authors: Greenwood A.D. , Leib-Mösch C. , Seifarth W.
Published: July 2005

Non-LTR retrotransposons are a diverse and taxonomically widely dispersed group of retroelements that can be divided into at least 14 distinguishable clades. Basal metazoans have not been examined in great detail for their retrotransposon content. In order to screen for the presence of reverse transcriptase (RT) related sequences in Cnidaria and Ctenophora, basal phyla of metazoans, PCR with highly degenerate oligonucleotides was performed and an RT-like sequence was identified from the sea anemone species Anemonia sulcata. Further screening identified a related element in another anemone species Actinia equina. Significant homology to non-LTR retrotransposon RTs was observed, particularly to L2-like elements of fish such as Maui. The sequence was not detected among other cnidarians and we have designated the A. sulcata and A. equina elements Abyss1 and Abyss2 respectively. Phylogenetic analysis of Abyss1 compared with members of 14 known non-LTR retroelement clades suggests that the sequence represents a novel L2 element.
Characterisation of pararetrovirus-like sequences in the genome of potato (Solanum tuberosum)
Authors: Hansen C.N. , Harper G. , Heslop-Harrison J.S.
Published: July 2005

Three families of pararetrovirus-like sequences were isolated from the genome of potato using PCR of a characteristic fragment extending from the end of the transactivator domain. The potato pararetrovirus-like sequences are abundant in the nuclear genome of potato as demonstrated by their hybridisation to high-molecular weight DNA in Southern transfers and by fluorescence in situ hybridisation. Sequencing of cloned PCR products demonstrated that the potato pararetrovirus-like sequences were similar to other pararetroviral sequences and also to some expressed sequences from tobacco and tomato, notably from callus and Agrobacterium-infected tissue. It is possible that the potato pararetroviral sequences defend against viral genes via silencing mechanisms, although, as in Petunia or banana, their transcription and recombination may cause infection under stress conditions.
A movable feast: diverse retrotransposons and their contribution to barley genome dynamics
Authors: Schulman A.H. , Kalendar R.
Published: July 2005

Cellular genes comprise at most 5% of the barley genome; the rest is occupied primarily by retrotransposons. Retrotransposons move intracellularly by a replicative mechanism similar to that of retroviruses. We describe the major classes of retrotransposons in barley, including the two nonautonomous groups that were recently identified, and detail the evidence supporting our current understanding of their life cycle. Data from analyses of long contiguous segments of the barley genome, as well as surveys of the prevalence of full-length retrotransposons and their solo LTR derivatives in the genus Hordeum, indicate that integration and recombinational loss of retrotransposons are major factors shaping the genome. The sequence conservation and integrative capacity of barley retrotransposons have made them excellent sources for development of molecular marker systems.
Fibrin Gel-Immobilized Primary Osteoblasts in Calcium Phosphate Bone Cement: In vivo Evaluation with Regard to Application as Injectable Biological Bone Substitute
Authors: Kneser U. , Voogd A. , Ohnolz J. , Buettner O. , Stangenberg L. , Zhang Y.H. , Stark G.B. , Schaefer D.J.
Published: July 2005

Osteogenic injectable bone substitutes may be useful for many applications. We developed a novel injectable bone substitute based on osteoblast-fibrin glue suspension and calcium phosphate bone cement (BC). Human osteoblasts were isolated from trabecular bone samples and cultured under standard conditions. Osteoblasts were suspended in fibrinogen solution (FS). BC was cured with thrombin solution. 8 × 4 mm injectable bone discs were prepared using silicon molds and a custom-made applicator device. Discs containing BC, BC/FS, or BC/FS/osteoblasts were implanted subcutaneously into athymic nude mice. After 3, 9 and 24 weeks, specimens were explanted and subjected to morphologic and biomechanical evaluation. In vitro fibrin gel-embedded osteoblasts displayed a differentiated phenotype as evidenced by alkaline phosphatase, collagen type 1 and von Kossa stains. A proportion of osteoblasts appeared morphologically intact over a 3-day in vitro period following application into the BC. BC/FS and BC/FS/osteoblast discs were sparsely infiltrated with vascularized connective tissue. There was no bone formation in implants from all groups. However, positive von Kossa staining only in BC/FS/osteoblast groups suggests engraftment of at least some of the transplanted cells. Biomechanical evaluation demonstrated initial stability of the composites. Young’s modulus and maximal load did not differ significantly in the BC/FS and BC/FS/osteoblast groups. The practicability of osteoblast-containing injectable bone could be demonstrated. The dense microstructure and the suboptimal initial vascularization of the composites may explain the lack of bone formation. Modifications with regard to enhanced osteoblast survival are mandatory for a possible application as injectable osteogenic bone replacement system.
Manipulation of the Phenylalanine Metabolism in Human Keratinocytes by Retroviral Mediated Gene Transfer
Authors: Christensen Rikke , Kolvraa Steen , Jensen Thomas G.
Published: July 2005

Phenylketonuria (PKU) is an inherited disease causing increased levels of phenylalanine in body fluids due to deficiency of hepatic phenylalanine hydroxylase (PAH) or other enzymes involved in the phenylalanine metabolism. With the long-term goal of using gene transfer to the skin to remove phenylalanine, we have previously shown that overexpression of PAH, catalyzing the hydroxylation of phenylalanine, and GTP cyclohydrolase (GTP-CH), involved in the formation of the necessary cofactor BH4,are required. Here we investigate whether manipulation of additional steps in the phenylalanine clearance pathway can further improve the phenylalanine uptake and metabolism. Transport of phenylalanine into human keratinocytes could be increased by overexpressing the two subunits LAT1 and 4F2hc of the large neutral amino acid transporter. The PAH enzyme activity was titrated by employing mutant PAH enzymes with different specific activity and by increasing the PAH copy number in transduced keratinocytes using a repeated transduction procedure. Finally, the intracellular tyrosine concentration was lowered by overexpression of tyrosinase converting tyrosine to dopaquinone. However, measured over a 24-hour period neither of these manipulations resulted in an increased phenylalanine uptake. These results suggest that other enzymes than GTP-CH, involved in BH4 synthesis and/or regeneration, can be rate-limiting in the genetically modified keratinocytes.
Relationship between Pituitary and Adipose Tissue after Hypothalamic Denervation in the Female Rat
Authors: Camihort Gisela , Gómez Dumm César , Luna Georgina , Ferese Celia , Jurado Susana , Moreno Griselda , Spinedi Eduardo , Cónsole Gloria
Published: July 2005

Neonatal administration of monosodium glutamate (MSG) to rats produces severe lesions in certain hypothalamic nuclei, with repercussions in different neuroendocrine axes, and serves as a model for their study. In addition, adipose tissue, as a target organ, is known to be directly related to several neurondocrine axes. We used 21-day-old female Sprague-Dawley rats that had received a neonatal treatment with MSG (4 mg/g body weight, i.p., from day 2 up to day 10 of age) in addition to control rats (injected with 10% NaCl solution, on a similar schedule). We performed a specific immunohistochemical study on each anterior-pituitary cell population, along with the morphometry of these cells and of the parietal and visceral adipose tissue, and measured the levels of serum leptin and triglycerides. The MSG animals evinced significant changes in volume density (VD), cell density (CD), and cell size (CS) in the corticotropes, thyrotropes, and LH gonadotropes, but not in the somatotropes, lactotropes, and FSH gonadotropes. The modification common to the three cell types was a hyperplasia, but with different results depending on cell size. Furthermore, in the MSG rats significant changes were also observed in the VD, CD, and CS of the adipose tissue, consisting of adipogenesis and decrease of adipocyte size in visceral fat, together with probable lipogenesis as judged by an increase in adipocyte size in the parietal fat. The serum levels of leptin and triglycerides appeared significantly higher in MSG animals. For the first time in this animal model, and at the level of three neuroendocrine axes, our results suggest changes that correlate hypothalamic damage, cellular pituitary alterations, and the response of the adipose tissue as a target organ for MSG insult.
Investigation of Cerebral Development and Injury in the Prematurely Born Primate by Magnetic Resonance Imaging and Histopathology
Authors: Inder Terrie , Neil Jeffrey , Kroenke Christopher , Dieni Sandra , Yoder Bradley , Rees Sandra
Published: July 2005

We summarize the preliminary results of brain histopathology and magnetic resonance imaging applied to a premature baboon model developed for evaluation of the pathogenesis and treatment of bronchopulmonary dysplasia. Cerebral development was assessed in 10 gestational control animals at time points of 125, 140 and 160 days of gestation (dg). On the basis of histopathology, conventional MRI and diffusion MRI, 125 dg is equivalent to 26–28 weeks of human gestation, 140 dg is equivalent to 30–32 weeks, and 160 dg is equivalent to term. Preliminary data are also presented for 33 experimental cases delivered at 125 dg, nursed for 2 weeks in an intensive care facility, and sacrificed at 139–140 dg. The commonest neuropathology in this cohort is white matter damage, manifest by reactive astrogliosis or activated microglia, and enlarged ventricular size. Subarachnoid, germinal matrix and intraventricular hemorrhages are also common. These preliminary results support the similarity of this model to the human preterm infant for both cerebral development and the pattern of cerebral injury. The prematurely born baboon appears an important model for the study of preterm human birth.
Neuronal Injuries Induced by Perinatal Hypoxic-Ischemic Insults Are Potentiated by Prenatal Exposure to Lipopolysaccharide: Animal Model for Perinatally Acquired Encephalopathy
Authors: Larouche A. , Roy M. , Kadhim H. , Tsanaclis A.M. , Fortin D. , Sébire G.
Published: July 2005

We developed an original rat model for neonatal brain lesions whereby we explored the sequential effects of infectious and hypoxic-ischemic aggressions. We investigated the influence of combined exposure to prenatal infection with neonatal hypoxic-ischemic insult. Infectious effect was produced by administrating lipopolysaccharide (LPS) intraperitoneally to pregnant rats starting on embryonic day 17. Hypoxia-ischemia (H/I) was induced in the pups at postnatal day 1 (P1) by ligature of the right common carotid artery followed by exposure to hypoxia (8% O2) for 3.5 h. Animals were randomized into four groups: (1) control group: pups born to mothers subjected to intraperitoneal saline injection; (2) LPS group: pups exposed in utero to LPS; (3) H/I group: pups exposed to postnatal hypoxia after ligation of the right carotid artery, and (4) H/I plus LPS group: in utero exposure to LPS followed by postnatal hypoxia after ligation of the right carotid artery. Neuropathological findings in pups examined at P3 and P8 showed that groups 2, 3, and 4 presented a pattern of neuronal injury similar to those characterized as ‘selective neuronal necrosis’ within the context of human perinatal encephalopathy. Neuronal cellular injuries were particularly seen in the neocortex, mainly in parasagittal areas. The extent of neuronal cell injury in the brain of rats exposed to postnatal H/I was significantly increased by antenatal exposure to LPS. This animal model provides an experimental means to explore the respective roles of anoxic and infectious components in the pathogenesis of perinatal brain lesions and consequent cerebral palsy.
Combined Deficiency of IL-1β18, but Not IL-1αβ, Reduces Susceptibility to Hypoxia-Ischemia in the Immature Brain
Authors: Hedtjärn Maj , Mallard Carina , Iwakura Yoichiro , Hagberg Henrik
Published: July 2005

Interleukin (IL)-1 and IL-18 belong to the IL-1 family. IL-18 deficiency has been shown to confer moderate protection after hypoxia-ischemia (HI) in the immature brain, while the contribution of the two isoforms of IL-1 (IL-1α and IL-1β) in neonatal HI brain injury has not been investigated previously. The aim of this study was to examine the contribution of the different members of the IL-1 family to neonatal HI damage. Unilateral HI was induced at postnatal day 9 in IL-1β, IL-1β18, and IL-1αβ knockout and wild-type mice and brain injury was evaluated 1 week later. IL-1β18-deficient mice showed 17% reduction in brain injury, while no significant reduction in injury was detected between any of the other groups. These results indicate that IL-18, but not IL-1β, or the combination of IL-1α and IL-1β, is a contributor to HI injury in the immature brain.
Glycolysis and Perinatal Hypoxic-Ischemic Brain Damage
Authors: Vannucci Robert C. , Brucklacher Robert M. , Vannucci Susan J.
Published: July 2005

To ascertain the regulation of glycolysis during perinatal hypoxia-ischemia, 7-day postnatal rats were subjected to unilateral common carotid artery ligation followed by hypoxia with 8% oxygen for up to 90 min. Brain concentrations of glucose, lactate, and key glycolytic intermediates were determined at specific intervals of hypoxia. During hypoxia-ischemia, anaerobic glycolysis increased to approximately 62% of its maximal capacity, which equates to a 135% stimulation of the glycolytic flux. The key regulatory enzymes, hexokinase, phosphofructokinase and pyruvate kinase, were all stimulated during hypoxia-ischemia, and there were no enzymatic rate limitations. The major rate-limiting step for glycolysis was the transport of glucose across the blood-brain barrier into the brain.
Expression of Erythropoietin and Its Receptor in the Brain of Late-Gestation Fetal Sheep, and Responses to Asphyxia Caused by Umbilical Cord Occlusion
Authors: Castillo-Meléndez Margie , Yan Edwin , Walker David W.
Published: July 2005

Asphyxia and hypoxia are common threats faced by the fetus in utero. In late-gestation fetal sheep, asphyxia produced by umbilical cord occlusion (UCO) results in widespread lipid peroxidation and apoptosis. Adaptive mechanisms that might limit fetal brain damage include induction of the hemopoietic cytokine, erythropoietin (EPO). In unanesthetized fetal sheep, we investigated if 1 or 2 bouts of brief asphyxia (UCO for 10 min) induced EPO and EPO type I receptor (EPO-R) expressions, with the second UCO repeated 48 h after the first. Fetal brains were recovered 48 h after either sham, 1 × or 2 × UCO at 129–133 (term ∼147) days of gestation and prepared for immunocytochemistry. In age-matched control brain, low levels of EPO and EPO-R proteins were present in oligodendrocytes (OLs), periventricular and cortical white matter (WM), with no EPO and very low EPO-R expression in neurons. After 1 × UCO, EPO and EPO-R expressions were increased in astrocytes (periventricular and cortical WM, striatum, corpus callosum), choroid plexus epithelial cells, scattered neurons in cortical layers IV–VI, hippocampal CA1 neurons, and in the molecular and granule layers of the cerebellum. After 2 × UCO, higher levels of EPO and EPO-R occurred in the periventricular and cortical WM, corpus callosum, hippocampal CA1, and in neurons of all cortical layers. Paradoxically, EPO and EPO-R were now lower in hippocampal CA1 neurons and cerebellar molecular and granule cell layers. Few OLs expressed EPO or EPO-R after 1 × or 2 × UCO. Thus, brief asphyxia induces EPO and EPO-R in fetal astrocytes, but only after repeated asphyxial insult in neurons. Whether this is a response to increased injury, or represents an adaptive response that limits further cell death and brain damage awaits further investigation.
Augmented Constitutive CREB Expression in the Nucleus accumbens and Striatum May Contribute to the Altered Behavioral Response to Cocaine of Adult Mice Exposed to Cocaine in utero
Authors: Guerriero Rejean M. , Rajadhyaksha Anjali , Crozatier Claire , Giros Bruno , Nosten-Bertrand Marika , Kosofsky Barry E.
Published: July 2005

Neuroadaptations occurring in the mesolimbic dopamine pathway following recurrent exposure to drugs of abuse have been correlated with a behavioral phenomenon known as behavioral sensitization. We have developed an animal model of prenatal cocaine exposure and, using a postnatal sensitization protocol, have examined the subsequent sensitivity of offspring to cocaine. Pregnant Swiss Webster dams were injected twice daily from embryonic day 8 to 17, inclusive, with cocaine (COC40: administered cocaine HCl at a dose of 40 mg/kg/day, and COC20: administered cocaine HCl at a dose of 20 mg/kg/day), or saline (SAL). The SPF40 group (saline pair-fed), a nutritional control group, was ‘pair-fed’ with COC40 dams. Activity was recorded for 30 min during a 3-day saline habituation, a 14-day ‘initiation’ phase, when animals received cocaine (15 mg/kg) or saline every other day, and following a 21-day ‘withdrawal’ period when all mice were challenged with cocaine. COC40 offspring, as compared with SAL controls, did not habituate to a novel environment, demonstrated increased cocaine-induced stereotypy on Coc 1 (first cocaine injection), and blunted locomotor sensitization on challenge as measured by the percentage of each animal’s baseline locomotion. Tissue samples of the nucleus accumbens (NAc) and striatum (Str) of all four prenatal treatment groups were examined to determine whether alterations in the transcription factor CREB or glutamate receptor subunit, GluR1, induced by prenatal cocaine treatment may have contributed to the altered behavioral responses. Immunoblot quantitation revealed significantly increased constitutive CREB expression in the NAc and Str of COC40 mice as compared with SAL controls. Such alterations in constitutive CREB levels may contribute to some of the behavioral differences reported in adult mice exposed to cocaine in utero.
Inflammation in Atherosclerosis and Other Conditions: A Response to Danger
Authors: Tsirpanlis George
Published: July 2005

In the last few years atherosclerosis has been recognized as an inflammatory process. Assessment of low-grade inflammation with indexes like C-reactive protein (CRP) is considered indicative and potentially predictive for this disease. On the other hand, in a large number of clinical studies, a grade of microinflammation has been found to be associated with numerous other processes that may be directly, indirectly or not related to atherosclerosis. The most interesting finding these studies have yielded is that innate immunity is activated in various, previously unexpected, conditions. This phenomenon is better explained by the application of a recently proposed immune activation mechanism, namely, the ‘danger model’. It seems that many conditions related to metabolic or homeostatic stress or to pro-atherosclerotic and pre-diabetic dysfunctions, established atherosclerosis or diabetes, but also other early tissue injury – like renal, pulmonary or connective tissue – and several exogenous stimuli, constitute ‘danger signals’ that induce inflammation which interacts with and complicates the above-mentioned processes. On this basis the complex relationships between CVD risk factors, atherosclerotic process, other tissue injury and inflammation is examined. The practical application of this hypothesis, namely the new clinical use of CRP as a sensitive – although not specific for atherosclerosis – index of low-grade inflammatory activity as well as to the atherosclerosis treatment are also discussed.
Prevalence of Moderate or Severe Left Ventricular Diastolic Dysfunction in Obese Persons with Obstructive Sleep Apnea
Authors: Sidana Jasdeep , Aronow Wilbert S. , Ravipati Gautham , Di Stante Brian , McClung John A. , Belkin Robert N. , Lehrman Stuart G.
Published: July 2005

We investigated prior to gastric bypass surgery the prevalence of left ventricular diastolic dysfunction (LVDD) by Doppler and tissue Doppler echocardiography in 14 obese women and in 6 obese men, mean age 45 years, with a mean body mass index of 49 ± 5 kg/m2 who had nocturnal polysomnography for obstructive sleep apnea (OSA). The Doppler and tissue Doppler echocardiographic data were analyzed blindly without knowledge of the clinical characteristics or whether OSA was present or absent. Of 20 patients, 8 (40%) had no OSA, 4 (20%) had mild OSA, and 8 (40%) had moderate or severe OSA. Moderate or severe LVDD was present in 4 of 8 patients (50%) with moderate or severe OSA and in none of 12 patients (0%) with no or mild OSA (p < 0.01). Obese patients with moderate or severe OSA have a higher prevalence of moderate or severe LVDD than obese patients with no or mild OSA.
Prospective Comparison of Valacyclovir and Oral Ganciclovir for Prevention of Cytomegalovirus Disease in High-Risk Renal Transplant Recipients
Authors: Reischig Tomáš , Opatrný Jr. Karel , Třeška Vladislav , Mareš Jan , Jindra Pavel , Švecová Miroslava
Published: July 2005

Aims: To compare the efficacy, costs and safety of oral ganciclovir and valacyclovir in the prophylaxis of cytomegalovirus (CMV) disease in renal transplant (RTx) recipients at high risk of CMV disease. Methods: A total of 83 patients were prospectively randomized to 3-month treatment with either oral ganciclovir (3 g/day) or oral valacyclovir (8 g/day). A 3rd group received no prophylaxis. Forty-nine patients were considered to be at high risk of CMV disease due to D+R– serologic status, OKT3/ATG treatment and/or acute rejection within 12 months after RTx. Twenty-three high-risk patients were treated with ganciclovir (GAN group), 17 patients with valacyclovir (VAL group), and 9 patients received no prophylaxis (C group). Results: No significant differences were found among the groups in their demographic characteristics, immunosuppressive protocols, D/R CMV serology, or CMV risk factors. The 12-month incidence of CMV disease was 89% in the C group compared with 9% in the GAN group and 6% in the VAL group (p < 0.001, GAN or VAL vs. C; p = 0.713, GAN vs. VAL). Treatment failure (death, graft loss, CMV disease or withdrawal from study) occurred in 17, 6, and 89% in the GAN, VAL, and C groups, respectively (p < 0.001, GAN or VAL vs. C; p = 0.285, GAN vs. VAL). The average CMV-associated costs per patient were EUR 3,161, 3,757, and 7,247 in the GAN, VAL, and C groups, respectively (p = 0.027). Conclusion: Valacyclovir and oral ganciclovir are equally effective in the prophylaxis of CMV disease in high-risk RTx patients. Both regimens are cost-effective and help reduce CMV-associated costs by nearly 50% compared with patients without prophylaxis.
Neuroendocrine Tumours of the Pancreas: Predictors of Survival after Surgical Treatment
Authors: Jarufe N.P. , Coldham C. , Orug T. , Mayer A.D. , Mirza D.F. , Buckels J.A.C. , Bramhall S.R.
Published: July 2005

Aims: Neuroendocrine tumours of pancreatic and duodenal origin (NETP) are rare and we present a significant experience from a single centre. Methods: Data was collected on 44 patients who underwent surgery between 1988 and 2002. Since 1997, data have been recorded prospectively on a dedicated database. Results: Twenty-four patients had functioning tumours (16 insulinomas, 3 gastrinomas, 2 somatostatinomas, 1 vipoma, 1 glucagonoma and 1 carcinoid tumour). Nine functioning tumours and 13 non-functioning had a malignant phenotype. Twenty pancreaticoduodenectomies, 9 local excisions, 7 distal and 2 total pancreatectomies, 5 bypasses and 1 exploratory laparotomy were performed. Fourteen patients (31.8%) had surgical complications, 1 died peri-operatively (2.3%). The overall actuarial survival for resected cases was 74.4 and 42.5% at 5 and 10 years, respectively. Lymph node invasion and metastases were significant predictors of survival by univariate analysis and only the presence of metastases retained significance on multivariate analysis. Conclusion: Surgical resection is the only curative treatment for NETP. Resection can be safely carried out in a specialist centre and is associated with good long-term survival. The presence of metastases was a significant predictive factor for survival in patients with NEPT in this series.
Immunologic Patterns in Allergic and Irritant Contact Dermatitis: Similarities
Authors: Dika Emi , Branco Nara , Maibach Howard I.
Published: July 2005

Long-standing tradition (and standard textbooks) suggest that separating irritation and allergic contact dermatitis (and their biologies) is straightforward. This overview examines this dogma, stressing that the similarities (at least in the efferent limbs) may be as great as the mechanistic differences.
Ultrastructural Study of Normal and Degenerating Nerve Fibers in the Protocerebral Tract of the Crab Ucides cordatus
Authors: Corrêa Clynton Lourenço , Allodi Silvana , Martinez Ana Maria Blanco
Published: July 2005

Wallerian degeneration is a very well described phenomenon in the vertebrate nervous system. In arthropods, and especially in crustaceans, nerve fiber degeneration has not been described extensively. In addition, literature shows that the events do not follow the same patterns as in vertebrates. In this study we report, by qualitative and quantitative ultrastructural analyses, the features and time course of the protocerebral tract degeneration following extirpation of the optic stalk. No remarkable changes were observed seven days after lesion. After 28 days the protocerebral tracts presented apparently preserved small and large diameter axons and some degenerating medium axons, with irregular contours and empty-looking aspect of the axoplasm. Forty days after the ablation of the optic stalks, both small (type I) and medium (type II and III) axons revealed signs of partial or total degeneration, but large nerve fibers (type IV) were still intact. After 45 days, the tract showed signs of advanced stage of degeneration and, apart from large axons, normal-looking fibers were almost absent. At these 3 last time points, degenerating axons displayed different electron densities and aspects, probably correlating to different onset times of the process. In addition, cells with granules in their cytoplasm, possibly hemocytes, were quite distinct, especially at 40 and 45 days after axotomy. These cells might share with glial cells the function of phagocytosis of cellular debris during the protocerebral tract degeneration. Quantitative analysis showed that the number of degenerating fibers increased significantly from 28 to 40 days after lesion, whereas the number of normal fibers decreased accordingly. Measurements of cross-sectional areas of normal and degenerating axons showed that types II and III (medium) start to degenerate before type I (small). Type IV (large) axons do not degenerate, even after 40 days. Therefore, we can conclude that degeneration in these afferent fibers starts late after axotomy, but proceeds at a faster rate afterwards until the complete degeneration of small and medium axons.
Sonic Motor Pathways in Piranhas with a Reassessment of Phylogenetic Patterns of Sonic Mechanisms among Teleosts
Authors: Ladich Friedrich , Bass Andrew H.
Published: July 2005

Sound production has evolved independently a number of times among teleost fishes. In most cases, sound is generated by fast contracting muscles that vibrate the swim bladder by way of their direct attachment (intrinsic muscles) or indirectly by way of other skeletal elements (extrinsic muscles). This study focuses on the red and black piranha, Pygocentrus nattereri and Serrasalmus rhombeus (superorder Ostariophysi, Order Characiformes), that have extrinsic swim bladder sonic muscles innervated by the third and fourth spinal nerves. This innervation pattern diverges from that found in most teleosts, including the closely related catfishes (Ostariophysi, Siluriformes), where sonic muscles are innervated by ventral occipital nerve roots that arise just caudal to the vagus nerve. Here, we tested the hypothesis that piranhas would also differ from most other teleosts in the location of their sonic motor neurons. Following biotin labeling of branches of the third and fourth spinal nerves that innervate the sonic muscles in the red and black piranha, sonic motor neurons were identified amongst other non-sonic motor neurons in the central part of the spinal cord, slightly ventrolateral to the central canal. To our knowledge, this is the first example of sonic motor neurons positioned entirely within the spinal cord. In the other species so far studied, sonic motor neurons form well-defined nuclei that extend from far caudal levels of the medulla into the rostral spinal cord and are located either within the ventral motor column or near the midline, close to or just ventrolateral to the fourth ventricle and central canal. A piranha-like pattern may be more widespread among characiforms and is likely present in other teleost orders, e.g., Sciaenidae (drumfishes), that also have sonic muscles innervated by spinal nerves.
Stimulatory Effect of Interleukin-1β on Growth Hormone Gene Expression and Growth Hormone Release from Rat GH3 Cells
Authors: Gong Feng-Ying , Deng Jie-Ying , Shi Yi-Fan
Published: July 2005

Our previous studies demonstrated that interferon gamma increases the human (h) growth hormone (GH) gene promoter activity in rat pituitary GH3 cells, and its regulatory mechanism may be different from the classical GH-releasing hormone-induced regulatory mechanism. Interleukin-1β (IL-1β) is thought to induce the release of GH by pituitary cells, but whether or not and by which mechanisms IL-1β regulates GH synthesis remains unclear. The purpose of our study was thus to investigate the effect of IL-1β on the hGH gene expression in GH3 rat pituitary tumor cells using stable transfection of the hGH promoter fused to a luciferase reporter gene. Our results showed that IL-1β (10–104 U/ml) increased GH secretion and synthesis and that 102 to 104 U/ml IL-1β promoted the luciferase expression in stable GH3 cells, with a maximal action of 1.61 times over that of controls. Among inhibitors of intracellular signaling transduction pathways, mitogen-activated protein kinase kinase (MAPKK/MEK) inhibitor PD98059 (40 µM) and p38 MAPK inhibitor SB203580 (5 µM)blocked completely the stimulatory effect of IL-1β, and the phosphoinositide 3-kinase inhibitor LY294002 (10 µM) blocked partially the induction of IL-1β. Western blot analysis demonstrated that IL-1β increased the activation of phosphorylated MEK and p38 MAPK in GH3 cells. Neither overexpression of Pit-1 nor inhibiting Pit-1 expression affected IL-1β induction of hGH promoter activity. To identify the DNA sequence that mediated the effect of IL-1β, six deletion constructs of hGH promoter were created. The stimulatory effect of IL-1β was abolished following deletion of the –196- to –132-bp fragment. In conclusion, our data show that IL-1β promotes GH secretion and synthesis by rat pituitary GH3 cells. The stimulatory effect of IL-1β on the hGH gene promoter appears to require the activation of MEK, p38 MAPK, and phosphoinositide 3-kinase and a fragment of promoter sequence that spans the –196- to –132-bp fragment of the gene, but is unrelated to the Pit-1 protein.
Chemokine Receptor CCR1: A New Target for Progressive Kidney Disease
Authors: Ninichuk Volha , Anders Hans-Joachim
Published: July 2005

Infiltrating leukocytes are thought to contribute to the progression of kidney disease. Locally produced chemokines guide circulating leukocytes into the kidney, which renders therapeutic blockade of respective chemokine receptors on the leukocyte surface as potential targets for the inhibition of renal leukocyte recruitment. By using mutant mice and specific antagonists, we found that chemokine receptor CCR1 has non-redundant functions for leukocyte adhesion to activated vascular endothelium and for transendothelial diapedesis. Most importantly, CCR1 blockade with a specific small molecule antagonist can improve injury in several types of progressive kidney disease models, even if treatment is initiated in advanced disease states. Identification of new targets may add to the therapeutic options in chronic kidney disease.
Primary Neuroendocrine Carcinoma of Inguinal Lymph Node
Authors: Biering H. , Bauditz J. , Brenner N. , Stein H. , Lochs H. , Strasburger C.J.
Published: July 2005

Ninety-seven percent of neuroendocrine carcinomas are located in the gastrointestinal tract or in the bronchopulmonary tree. Inguinal lymph nodes as the primary tumor site for neuroendocrine carcinoma represent a very unusual location, and have only been described in 2 patient series in the literature. A 64-year-old, previously healthy, Caucasian female presented with a 2-month history of an enlarged inguinal lymph node on the right side. The removed lymph node showed histological and immunohistochemical characteristics of neuroendocrine differentiation (positive for synaptophysin, cytokeratin 20, neuron-specific enolase and chromogranin A). Although extensive investigations including repeated CT and NMR scans, classical endoscopy, wireless capsule endoscopy of the small intestine, octreotide- and MIBG scintigraphy were performed, no other primary tumor was found. Furthermore, there was no evidence of Merkel cell carcinoma on dermatological examinations. A possible explanation for the presence of neuroendocrine carcinomas within the lymph nodes is malignant transformation of preexisting intranodal epithelial nests, which have previously been described in lymph nodes located close to the salivary glands, thyroid gland, breast tissue and pancreas. Since the surgical removal of the affected lymph node, the patient has now been disease-free for 42 months. We therefore consider our case to represent a primary undifferentiated neuroendocrine carcinoma in an inguinal lymph node.
CD2AP Expression in a Renal Ischemia/Reperfusion Injury Model and Analysis of Its Related Genes Using Overexpression and RNA Interference Technique
Authors: Nishimura Sayoko , Yoshida Takumi , Sugiura Hidekazu , Shirota Satsuki , Tsuchiya Ken , Nihei Hiroshi
Published: July 2005

Background: CD2-associated protein (CD2AP) is a ubiquitously expressed 80-kDa intracellular protein, and has been speculated to act as an intracellular signaling pathway between plasma membrane proteins and cytoskeleton proteins. CD2AP expression has been reported in both the glomerulus and tubular epithelium in the kidney, and CD2AP knockout mice exhibit congenital nephrotic syndrome. However, the precise properties and its role in the renal tubules have not been clarified. Methods: We used an established rat model of ischemic/reperfusion renal injury (IRI) to examine the expression of CD2AP by real-time PCR, Western blotting, and immunohistochemistry. We also investigated the expression of genes related to apoptosis and cell proliferation in mouse collecting duct-derived cells (M1 cells) transfected with full-length of CD2AP cDNA or short interfering RNA. Results: CD2AP mRNA and protein expression had significantly increased in the IRI kidney. Real-time PCR indicated that expression of genes regulating apoptosis, such as B-Raf and Caspase-12, and genes regulating cell proliferation factors, CDC2, was decreased in CD2AP-overexpressing M1 cells and increased in CD2AP-interfered M1 cells. Conclusions: These results suggest that CD2AP expression was increased following renal ischemia and that CD2AP may be related to the process of cell repair and/or cell differentiation following injury.
Cardiovascular Risk in Relation to α-Adducin
Gly460Trp
Polymorphism and Systolic Pressure
Authors: Li Yan , Thijs Lutgarde , Kuznetsova Tatiana , Zagato Laura , Struijker-Boudier Harry , Bianchi Giuseppe , Staessen Jan A.
Published: July 2005

Preliminary evidence from 1 case-control study suggested that in hypertensive patients, the α-adducin
460Trp
allele might be associated with a 2-fold higher risk of coronary heart disease. In a prospective population study, we investigated whether the α-adducin
Gly460Trp
polymorphism predicted mortality and morbidity. From August 1985 until July 2003, we randomly recruited 2235 Belgian residents. We obtained information on vital status (until July 1, 2004) and the incidence of events via registries and repeat examinations (median 3). In Cox regression, before and after adjustment for other risk factors, we found strong interaction between systolic blood pressure at baseline, analyzed as a continuous variable, and the α-adducin polymorphism in relation to total (
P
=0.01) and cardiovascular mortality (
P
=0.007) and all cardiovascular (
P
=0.003), cardiac (
P
=0.001), and coronary events (
P
=0.03). The hazard ratio for total mortality associated with the
Trp
allele relative to
GlyGly
homozygosity was 2.30 (95% confidence interval, 1.12 to 4.72;
P
=0.02) in patients with stage-2 systolic hypertension (≥160 mm Hg) and 0.88 (0.61 to 1.26;
P
=0.48) in the other participants. For all cardiovascular complications, these estimates were 2.94 (1.28 to 6.74;
P
=0.01) and 0.83 (0.58 to 1.20;
P
=0.32), respectively. For all cardiovascular events, the positive predictive value and the attributable risk associated with the
Trp
allele in patients with stage-2 systolic hypertension were 76.9% and 44.3%, respectively. In conclusion, the α-adducin
Gly460Trp
polymorphism, in combination with systolic blood pressure, is a strong predictor of cardiovascular mortality and morbidity.
Prevalence of Cardiovascular Disease Risk Factor Clustering Among the Adult Population of China
Authors: Gu Dongfeng , Gupta Anjali , Muntner Paul , Hu Shengshou , Duan Xiufang , Chen Jichun , Reynolds Robert F. , Whelton Paul K. , He Jiang
Published: July 2005

Background—

The prevalence of cardiovascular disease (CVD) risk factors has been increasing in China.

Methods and Results—

We examined the prevalence of CVD risk factor clustering among Chinese adults aged 35 to 74 years with data from the International Collaborative Study of Cardiovascular Disease in Asia (InterAsia), a cross-sectional survey of a nationally representative sample (n=14 690) conducted during 2000 to 2001 and compared these data with those of US adults from the National Health and Nutrition Examination Survey of 1999 to 2000. Overall, 80.5%, 45.9%, and 17.2% of Chinese adults had ≥1, ≥2, and ≥3 modifiable CVD risk factors (dyslipidemia, hypertension, diabetes, cigarette smoking, and overweight), respectively. By comparison, 93.1%, 73.0%, and 35.9% of US adults had ≥1, ≥2, and ≥3 of these risk factors, respectively. In a multivariate model including age, sex, and area of residence, the odds ratio (95% confidence interval [CI]) of having ≥1, ≥2, and ≥3 CVD risk factors versus none of the studied risk factors was 2.61 (95% CI, 2.09 to 3.27), 3.55 (95% CI, 2.77 to 4.54), and 4.97 (95% CI, 3.67 to 6.74), respectively, for Chinese adults 65 to 74 years old versus 35 to 44 years old; 3.65 (95% CI, 3.21 to 4.15), 4.67 (95% CI, 4.06 to 5.38), and 5.60 (95% CI, 4.70 to 6.67), respectively, for men compared with women; 1.18 (95% CI, 1.07 to 1.30), 1.34 (95% CI, 1.21 to 1.50), and 1.84 (95% CI, 1.60 to 2.12), respectively, for urban compared with rural residents; and 1.98 (95% CI, 1.76 to 2.22), 2.75 (95% CI, 2.42 to 3.13), and 4.36 (95% CI, 3.68 to 5.18), respectively, for residents of northern compared with southern China.

Conclusions—

Clustering of CVD risk factors is common in China. Prevention, detection, and treatment of CVD risk factor clustering should be an important component of a national strategy to reduce the increasing burden of CVD in China.
Real-Time Magnetic Resonance Imaging–Guided Stenting of Aortic Coarctation With Commercially Available Catheter Devices in Swine
Authors: Raval Amish N. , Telep James D. , Guttman Michael A. , Ozturk Cengizhan , Jones Michael , Thompson Richard B. , Wright Victor J. , Schenke William H. , DeSilva Ranil , Aviles Ronnier J. , Raman Venkatesh K. , Slack Michael C. , Lederman Robert J.
Published: July 2005

Background—

Real-time MR imaging (rtMRI) is now technically capable of guiding catheter-based cardiovascular interventions. Compared with x-ray, rtMRI offers superior tissue imaging in any orientation without ionizing radiation. Translation to clinical trials has awaited the availability of clinical-grade catheter devices that are both MRI visible and safe. We report a preclinical safety and feasibility study of rtMRI-guided stenting in a porcine model of aortic coarctation using only commercially available catheter devices.

Method and Results—

Coarctation stenting was performed wholly under rtMRI guidance in 13 swine. rtMRI permitted procedure planning, device tracking, and accurate stent deployment. “Active” guidewires, incorporating MRI antennas, improved device visualization compared with unmodified “passive” nitinol guidewires and shortened procedure time (26±11 versus 106±42 minutes;
P
=0.008). Follow-up catheterization and necropsy showed accurate stent deployment, durable gradient reduction, and appropriate neointimal formation. MRI immediately identified aortic rupture when oversized devices were tested.

Conclusions—

This experience demonstrates preclinical safety and feasibility of rtMRI-guided aortic coarctation stenting using commercially available catheter devices. Patients may benefit from rtMRI in the future because of combined device and tissue imaging, freedom from ionizing radiation, and the ability to identify serious complications promptly.
Is It Content or Style? An Evaluation of Two Competitive Measurement Models Applied to a Balanced Set of Ethnocentrism Items
Authors: Cambré Bart , Welkenhuysen-Gybels Jerry , Billiet Jaak
Published: July 2005

Attitude surveys often use sets of items with identical response scales (e.g., in Likert format) in order to formulate attitude constructs. There is considerable evidence that such a response format can be susceptible to acquiescence bias (i.e., the tendency to agree with survey questions). The specification of a style factor (acquiescence) in measurement models can result in well-fitted factorial invariant models for cross-cultural surveys. Attempts to model acquiescence are confronted with the phenomenon that models with a positive and a negative factor appear to be as likely as models with a bipolar factor and a style factor. We will evaluate the two competitive measurement models, applied to a balanced set of ethnocentrism items from the 1999 Religious and Moral Pluralism (RAMP) dataset. It is argued that the competing measurement models should be evaluated in the context of a theoretically meaningful nomological network.
The Globalization of Environmental Protection: The Case of Environmental Impact Assessment
Authors: Hironaka Ann
Published: July 2005

Much of the literature on environmental protection focuses on domestic actors and domestic political activity. However, the degree to which environmental policies are influenced by international organizations and agendas is often overlooked. In the case of environmental policies in less developed countries, the role of the international system is particularly essential. Indeed, the international system is often the primary motivator of environmental protection policies in less developed countries. This paper demonstrates the strength of international influence in the case of one particular policy, Environmental Impact Assessment legislation. It argues that international environmental organizations, the international development bank community, and the international science community, have had central importance in the diffusion of Environmental Impact Assessment legislation, outweighing other factors such as the size of domestic environmental support or the degree of environmental degradation. This argument is supported by the results of an event history statistical analysis.
Religious Parties and Politics in Pakistan
Authors: Tanwir Farooq
Published: July 2005

In October 2002, for the first time in Pakistan’s history, a sizeable share of the population voted for religious parties. Some Pakistanis, and most Western analysts, interpret this as signaling the rise of a major fundamentalist religious movement. We suggest, however, that in large part, this phenomenon can be viewed as a protest vote, made as a rebuke to the major political parties, which have failed so far to provide any solutions to Pakistan’s poverty and misery. This article examines the viewpoints of various analysts, representing various schools of thought in Pakistan.