bluuebunny/crossref_metadata_2025 huggingface dataset:
Conserved synteny of mammalian imprinted genes in chicken, frog, and fish genomes
Authors: Dünzinger U. , Haaf T. , Zechner U.
Published: July 2007

Conservation of synteny of mammalian imprinted genes between chicken and human suggested that highly conserved gene clusters were selected long before these genes were recruited for genomic imprinting in mammals. Here we have applied in silico mapping of orthologous genes in pipid frog, zebrafish, spotted green and Japanese pufferfish to show considerable conservation of synteny in lower vertebrates. More than 400 million years ago in a common ancestor of teleost fish and tetrapods, ‘preimprinted’ chromosome regions homologous to human 6q25, 7q21, 7q32, 11p15, and 15q11→q12 already contained most present-day mammalian imprinted genes. Interestingly, some imprinted gene orthologues which are isolated from imprinted clusters in mouse and human could be linked to preimprinted regions in lower vertebrates, indicating that separation occurred during mammalian evolution. On the contrary, newly arisen genes by segmental duplication in the mammalian lineage, i.e. SNRPN and FRAT3, were transposed or translocated to imprinted clusters and recruited for parent-specific activity. By analysis of currently available sequences of non-mammalian vertebrates, the imprinted gene clusters homologous to human chromosomes 14q32 and 19q12 are only poorly conserved in chicken, frog, and fish and, therefore, may not have evolved from ancestral preimprinted gene arrays. Evidently, evolution of imprinted gene clusters is an ongoing and dynamic process in mammals. In general, imprinted gene orthologues do not show a higher degree of synteny conservation in vertebrates than non-imprinted genes interspersed with or adjacent to an imprinted cluster.
A functional genomics approach to the study of avian innate immunity
Authors: Keeler, Jr C.L. , Bliss T.W. , Lavrič M. , Maughan M.N.
Published: July 2007

A second-generation 4,959 element cDNA microarray has been created and evaluated for its potential use in examining the avian innate immune response. The elements in this array were obtained from EST libraries of stimulated avian PMNC-derived monocytes/macrophages and supplemented by genes of interest from several specific innate immune pathways. The elements are spotted in triplicate resulting in 14,877 total spots per slide. The avian innate immunity microarray (AIIM) contains 25 avian interleukin, chemokine, and cytokine elements. The array also contains elements for several innate immune pathways, including genes involved in the Toll-like receptor (TLR) pathway (including six of the currently known avian TLR receptors), avian interferon/antiviral response pathway genes, and genes involved in apoptosis, antigen presentation and the oxidative burst. The AIIM can be used to evaluate global gene expression patterns in a number of immunologically relevant tissues and in chickens, turkeys and ducks. The array has also been evaluated for its ability to monitor the avian immune response to both bacterial (avian pathogenic Escherichia coli) and viral (avian influenza) avian pathogens.
Manipulation of thyroid status and/or GH injection alters hepatic gene expression in the juvenile chicken
Authors: Wang X. , Carré W. , Saxton A.M. , Cogburn L.A.
Published: July 2007

Both thyroid hormone (T3) and growth hormone (GH) are important regulators of somatic growth in birds and mammals. Although T3-mediated gene transcription is well known, the molecular basis of T3 interaction with GH on growth and development of birds remains unknown. In earlier studies, we discovered that exogenous GH alone increased accumulation of visceral fat in young chickens, while the combination of GH injections and dietary T3 worked synergistically to deplete body fat. In the present study, cDNA microarray and quantitative RT-PCR analyses enabled us to examine hepatic gene expression in young chickens after chronic manipulation of thyroid status and GH injection alone or in combination with T3. Thyroid status modulates expression of common and unique sets of genes involved in a wide range of molecular functions (i.e., energy metabolism, storage and transport, signal transduction, protein turnover and drug detoxification). Hepatic expression of 35 genes was altered by hypothyroidism (e.g., ADFP, ANGPTL3, GSTΑ, CAT, PPARG, HMGCL, GHR, IGF1, STAT3, THRSPα), whereas hyperthyroidism affected expression of another cluster of 13 genes (e.g., IGFBP1, KHK, LDHB, BAIA2L1, SULT1B, TRIAD3). Several genes were identified which have not been previously ascribed as T3 responsive (e.g., DEFB9, EPS8L2, ARHGAP1, LASS2, INHBC). Exogenous GH altered expression of 17 genes (e.g., CCAR1, CYP2C45, GYS2, ENOB, HK1, FABP1, SQLE, SOCS2, UPG2). The T3+GH treatment depleted the greatest amount of body fat, where 34 differentially expressed genes were unique to this group (e.g., C/EBP, CDC42EP1, SYDE2, PCK2, PIK4CA, TH1L, GPT2, BHMT). The marked reduction in body fat brought about by the T3+GH synergism could involve modulation of hormone signaling via altered activity of the Ras superfamily of molecular switches, which control diverse biological processes. In conclusion, this study provides the first global analysis of endocrine (T3 and GH) regulation of hepatic gene transcription in the chicken.
Biotechnology and the chicken B cell line DT40
Authors: Bachl J. , Caldwell R.B. , Buerstedde J.-M.
Published: July 2007

Protein optimization is a major focus of the biotech and pharmaceutical industry. Various in vitro technologies have been developed to accelerate protein evolution and to achieve protein optimization of functional characteristics such as substrate specificity, enzymatic activity and thermostability. The chicken B cell line DT40 diversifies its immunoglobulin (Ig) gene by gene conversion and somatic hypermutation. This machinery can be directed to almost any gene inserted into the Ig locus. Enormously diverse protein libraries of any gene of interest can be quickly generated in DT40 by utilizing random shuffling of complex genetic domains (gene conversion) and by the introduction of novel non-templated genetic information (random mutagenesis). The unique characteristics of the chicken cell line DT40 make it a powerful in-cell diversification system to improve proteins of interest within living cells. One essential advantage of the DT40 protein optimization approach is the fact that variants are generated within an in-cell system thus allowing the direct screening for desired features in the context of intracellular networks. Utilizing specially designed selection strategies, such as the powerful fluorescent protein technology, enables the reliable identification of protein variants exhibiting the most desirable traits. Thus, DT40 is well positioned as a biotechnological tool to generate optimized proteins by applying a powerful combination of gene specific hypermutation, gene conversion and mutant selection.
The avian immune genome – a glass half-full or half-empty?
Authors: Kaiser P.
Published: July 2007

Although in broad terms the avian immune response is remarkably similar to that of mammals, when one looks at specifics birds have a different repertoire of immune organs, cells and molecules compared to those characterized in mammals. Birds lack organized lymph nodes, yet have the Bursa of Fabricius. Birds lack neutrophils and functional eosinophils, yet have a distinct group of polymorphonuclear granulocytes known as heterophils. Birds also have a different repertoire of cytokines, chemokines, Toll-like receptors, defensins and integrins, as detailed in this review.
The chicken as a model for embryonic development
Authors: Davey M.G. , Tickle C.
Published: July 2007

The traditional strength of chicken embryos for studying development is that they are readily manipulated. This has led to some major discoveries in developmental biology such as the demonstration that the neural crest gives rise to almost the entire peripheral nervous system and the identification of signalling centres that specify the pattern of structures in the central nervous system and limb. More recently with the burgeoning discovery of developmentally important genes, chicken embryos have provided useful models for testing function. Uncovering the molecular basis of development provides direct links with clinical genetics. In addition, since many genes that have crucial roles in development are also expressed in tumours, basic research on chickens has implications for understanding human health and disease. Now that the chicken genome has been sequenced and genomic resources for chicken are becoming increasingly available, this opens up opportunities for combining these new technologies with the manipulability of chicken embryos and also exploiting comparative genomics.
Potential application of sperm bearing female-specific chromosome in chickens
Authors: Shimada K. , Valdez Jr. M.B. , Mizutani M. , Namikawa T.
Published: July 2007

This paper reviews studies on sex reversal experiments in chickens, production of sperm bearing a female-specific chromosome, its application for poultry resources and finally a mechanism of sex differentiation of gonads in the chicken.
Fanconi anemia: genetic analysis of a human disease using chicken system
Authors: Takata M. , Kitao H. , Ishiai M.
Published: July 2007

Fanconi anemia (FA) is a rare hereditary disorder characterized by skeletal abnormalities, bone marrow failure, and an increased incidence of cancer. The basic cellular abnormality in FA has been postulated to lie in the DNA repair mechanisms because cells from FA patients display chromosomal breakage, which is particularly remarkable following induction of DNA crosslinks. However, experimental evidence for this hypothesis has been lacking. To test whether DNA repair is really defective in FA cells, we disrupted several FA genes in chicken B cell line DT40. By measuring efficiency of gene conversion and hypermutation at the Immunoglobulin locus, we have shown that DT40 FA mutant cell lines exhibited defects in homologous DNA recombination, and possibly, translesion synthesis. However, levels of sister chromatid exchange, another important cellular event mediated by HR, were not reduced, possibly indicating the role of FA genes only in a subpathway of HR. Our results indicate that chicken DT40 cells could be highly useful in molecular dissection of basic biochemical processes, which are deficient in a human genetic disorder.
Polymorphisms of the chicken antiviral MX gene
Authors: Watanabe T.
Published: July 2007

The Mx gene was originally found in laboratory mice in an infection experiment using influenza virus (Lindermann, 1962). Almost all of the mouse strains in that experiment died from the infection, and only the A2G strain had resistance to the virus. This resistant character was shown to be inherited as a single autosomal dominant trait (Lindermann et al., 1963; Lindermann, 1964; Haller et al., 1979). A congenic mouse strain was established by introducing the Mx+ allele of the A2G resistant strain into the Mx– sensitive inbred strain BALB/c (Staeheli et al., 1984). By immunizing parental BALB/c mice with extracts of interferon (IFN)-treated cultured cells from congenic BALB/c-Mx+ mice, a specific antibody against Mx protein was obtained (Horisberger et al., 1983; Staeheli et al., 1985). The Mx protein was detected in the nucleus of IFN-α/β-treated mouse cells by immunofluorescence using the anti-Mx antibody (Dreiding et al., 1985). Thereafter, by using the antibody as an indicator, cDNA encoding the Mx protein was cloned from a cDNA library constructed from IFN-treated cells of congenic BALB/c-Mx+ mice (Staeheli et al., 1986a). IFN-treated Mx+ mouse cells contained a 3.5-kb Mx mRNA in the Northern blot, while Mx– cells failed to express the transcript. The functional Mx+ gene from an A2G mouse was found to contain 14 exons and encode 631 amino acids. The Mx– allelic mouse strains were found to be missing sequence of exons 9 through 11 or to contain a point mutation that converts lysine at position 389 to a stop codon (Staeheli et al., 1988). If these polymorphisms of the Mx gene could be detected in domestic animals, it would be possible to produce breeds that show resistance to infectious diseases.
Genomics and Marek’s disease virus
Authors: Burnside J. , Morgan R.W.
Published: July 2007

Marek’s disease virus (MDV), a lymphotrophic alphaherpesvirus of chickens, causes a disease that is characterized by tumor formation, immunosuppression and neurological disorders. Recent developments in chicken genomics have been applied to studies of MDV and have advanced our understanding of both the virus and the disease it causes. We have constructed and used microarrays to identify host genes that are up-regulated in chicken embryo fibroblasts infected with MDV as a first step to catalog the host response to infection. An additional level of gene regulation lies at the level of microRNAs (miRNAs). miRNAs are a class of small (∼22 nt) regulatory molecules encoded by a wide variety of organisms, including some viruses, that block translation or induce degradation of specific mRNAs. Herpesviruses, which replicate in the nuclei of infected cells, are a particularly important class of viruses that express miRNAs. miRNAs from two of the oncogenic herpesviruses; namely, Kaposi’s sarcoma herpesvirus (KSHV) and Epstein-Barr virus (EBV) have been cataloged. We recently identified MDV-encoded miRNAs. One cluster of miRNAs flanks the meq oncogene, and a second cluster maps to the latency associated transcript (LAT) region of the genome. The LATs are encoded anti-sense to the ICP4 immediate early gene, and the meq gene, which is unique to pathogenic serotypes of MDV, is the most likely oncoprotein or co-oncoprotein encoded by MDV. The conservation of these sequences is suggestive of an important role in pathogenesis.
Food Pyramid of the Swiss Society for Nutrition
Authors: Walter Paul , Infanger Esther , Mühlemann Pascale
Published: July 2007

The Swiss Society for Nutrition issued its Food Pyramid in 2005. It was updated according to the latest scientific evidence and is in principal agreement with food-based guidelines of other countries. It has also been officially endorsed by the Swiss government. The food pyramid stands for a balanced diet that guarantees the body a sufficient supply of energy, essential nutrients and protective substances. Food from the lower levels of the pyramid should be eaten in larger quantities, and those from the higher levels in smaller quantities. The six levels from top down represent the following food groups: sweets, salty snacks and sweetened or alcoholic drinks; oils, fats and nuts; milk, dairy products, meat, fish and eggs; whole grain products and pulses, other cereals and potatoes; fruit and vegetables; beverages. A basic principle to be communicated by the food pyramid is that there are no good or bad foods but that the relative amounts to be consumed play a key role for our health. The key message is to eat a diet that is as varied as possible and which considers foods of each pyramid level in the right amounts. The recommendations do not need to be followed every day, but should be observed on a long-term basis, e.g. a whole week. Liquid intake is an exception; liquids should be consumed on a daily basis. It is also very important to keep a healthy body weight by daily exercise as indicated by the icons on the side of the Swiss Food Pyramid.
Dissemination of Nutritional Knowledge in Germany – Nutrition Circle, 3D Food Pyramid and 10 Nutrition Guidelines
Authors: Stehle Peter
Published: July 2007

Background/Aims: Presentation of the general concept of the German Nutrition Society for a successful dissemination of nutritional knowledge. Methods: Evaluation of actual material used for nutrition education and teaching. Results: In Germany, different validated instruments on the basis of actual scientific evidence are available. Quantitative aspects can be easily enlightened with the help of the Nutrition Circle. Information concerning optimal personal behavior (lifestyle) is transported using a flyer with 10 Nutrition Guidelines. The 3D Food Guide Pyramid is an encouraging new instrument to establish new teaching programs with a high level of acceptance. It is planned to establish target-specific food guide pyramids, e.g. for adolescents, aged persons (considering gender), people with increased physical activity and others. Tests with target groups (health professionals, teachers, young consumers) showed a high rate of acceptance and demonstrated successful application of the German concept of dissemination of dietary guidelines. Conclusion: Using modern communication technology, it is feasible for the consumers and the health professionals to download gender- and age-specific scientific information as well as validated tools for successful nutrition education.
Visualization of Food-Based Dietary Guidelines – Examples
Authors: Koenig Juergen S.
Published: July 2007

Food-based dietary guidelines (FBDGs) are the primary instrument for the translation of nutrient-based guidelines into practice for the general population. The key concepts for the development of FBDGs as outlined by the report of a joint FAO/WHO consultation in 1996 are to address dietary patterns, to be practical, to be comprehensible, and to be culturally acceptable. These key concepts need to be considered particularly when planning to visualize FBDGs, since the visualization is the major mode of information transfer and the first – and quite frequently the only – contact with the guidelines. For the visualization of dietary patterns it is recommended that total diets rather than nutrients or individual foods should be addressed, although there are some examples which were successful in addressing specific foods and food groups. The design of FBDGs should be flexible for use by people with different lifestyles as well as people of different ages and with different physiological conditions. However, the visualization of FBDGs is a marketing instrument, which differs in no way from regular and commercial marketing instruments. To be successful, these instruments need to be specific for the target population. With increasing power, influence, and coverage of computer-based instruments, the individualization of FBDGs has been facilitated. New strategies have therefore been developed to provide guidelines tailored to individual needs and preferences, as can be seen in the concept of the new food guide pyramids by the US Department of Agriculture. Whether these guidelines are successful needs to be awaited, their major problem being initiative required from the consumer rather than delivering the information appropriately and conveniently to the target population.
Impact of Food Processing on the Implementation of Dietary Guidelines
Authors: Frisch G. , Elmadfa I.
Published: July 2007

Community nutrition offers a wide range of possibilities to increase the health-promoting potential of meals. Yet, the potential for increasing the nutritional quality and the health-promoting value of food is not fully utilized, particularly in the setting of canteen kitchens. There are more than 3,000 canteen kitchens in Austria, and their meal service may have a considerable impact on the well-being of approximately 1.5 million consumers. Nutrient-based dietary guidelines act as an interface between theory and practice and form the basis for the development of recipes and for professional menu planning. In this regard, food processing plays a central role for the implementation of dietary guidelines. It is a common challenge for nutritionists and cooks to provide meals that are both tasty and healthy. Optimization with regard to the health value of community nutrition means reorientation and is composed of two steps: (1) optimization of nutrient and energy contents of menus through a well-balanced diet composition and (2) best-possible preservation of nutrients through professional food processing. Nutrient content optimization in food needs to consider all areas of community nutrition, including a target group oriented nutrient calculation, as well as planning and development of tasty and healthy meals and the highest possible nutrient retention during the entire food preparation process.
Bloodless (Liver) Surgery? The Anesthetist’s View
Authors: Hofland Jan , Henny C. Pieter
Published: July 2007

Background/Aims: An increasing amount of literature concerning blood conservation, restrictive transfusion strategies, pharmacological manipulation of the hemostatic and fibrinolytic systems, minimal invasive surgery, local hemostatic agents and guidelines for blood transfusion, is being published each year. Is ‘bloodless (liver) surgery’ or rather minimization of perioperative blood loss and transfusion requirement necessary? Methods: To answer this question, we studied key articles and checked cross-references with the support of PubMed and the Cochrane Database of systematic reviews. Results: At present there is still a need to reduce the use of blood. Pre-donation, set of transfusion triggers, (non-)pharmacological approaches to decrease surgical blood loss, hemodilution techniques, peri- and postoperative cell salvage and postoperative re-transfusion can contribute to the success of a bloodless (liver) surgery program. Conclusion: We conclude that a multidisciplinary effort has to be made through the entire chain, from the outpatient clinic through discharge from the hospital, with the utmost exertion of all team members in which surgeons play a key role in the adaptation of a bloodless (liver) surgery program to the specific needs of patients.
Vascular Occlusion Techniques during Liver Resection
Authors: van Gulik Thomas M. , de Graaf Wilmar , Dinant Sander , Busch Olivier R.C. , Gouma Dirk J.
Published: July 2007

Control of bleeding from the transected liver basically consists of vascular inflow occlusion and control of hepatic venous backflow from the caval vein. Central venous pressure determines the pressure in the hepatic veins and is an extremely important factor in controlling blood loss through venous backflow. Vascular inflow occlusion (Pringle maneuver) involves clamping of the portal vein and the hepatic artery in the hepatic pedicle and gives rise to postischemic, reperfusion injury. Several strategies have been devised to reduce reperfusion injury (pharmacological interventions) or to increase ischemic tolerance of the liver (ischemic preconditioning). Intermittent clamping is recommended in complex liver resections or in patients with diseased livers. The combination of occlusion of vascular inflow and outflow of the liver results in total hepatic vascular exclusion (THVE) and is mainly used in tumors invading the caval vein. During THVE the liver can be cooled by hypothermic perfusion allowing for extended ischemia times. Selective THVE entails clamping of the main hepatic veins in their extrahepatic course, thus preserving caval flow. Safe liver surgery requires knowledge of the regular techniques of vascular occlusion for ‘on demand’ use when necessitated to reduce blood loss.
Aprotinin and Nafamostat Mesilate in Liver Surgery: Effect on Blood Loss
Authors: Pereboom Ilona T.A. , de Boer Marieke T. , Porte Robert J. , Molenaar I. Quintus
Published: July 2007

The origin of blood loss during liver surgery is multifactorial. Surgical skill, technique, anesthesiological care, but also hyperfibrinolysis have been shown to play a role in the origin of bleeding during partial hepatectomy and liver transplantation. The latter has provided the scientific basis for the prophylactic use of antifibrinolytic drugs, such as aprotinin and nafamostat mesilate in liver surgery. Recently however, concern has been voiced about potential risks associated with aprotinin, including renal failure and thromboembolic events. In this review we discuss the efficacy and safety issues of aprotinin and nafamostat mesilate in liver surgery. We identified a total of 19 studies on the use of either aprotinin or nafamostat mesilate in liver surgery reported in the time period between 1966 and July 2006. The use of aprotinin or nafamostat mesilate in partial hepatectomies was studied in three studies. In 16 studies the use of aprotinin in liver transplantation was investigated. With respect to partial hepatectomy, improvements in surgical technique and anesthesiological care seem to be more important in reducing blood loss than the use of the antifibrinolytic drugs. Aprotinin may be indicated in a selected group of patients with cirrhosis undergoing liver resection, but further studies in this specific group of patients will be needed. In liver transplantation, the use of aprotinin is associated with a significant reduction in blood loss and transfusion requirements of around 30–40%. Results of prospective studies do not provide support for safety concerns as no increased risk for thromboembolic events or renal dysfunction has been observed in liver transplant patients treated with aprotinin. In conclusion, there is currently no scientific support for the routine use of aprotinin or nafamostat mesilate in patients undergoing partial hepatectomy, whereas the efficacy of aprotinin in liver transplantation is well established. More studies will be needed to address the safety aspects of aprotinin in patients undergoing liver surgery in more detail.
Experience with TissueLink™ – Radiofrequency-Assisted Parenchymal Division
Authors: Hutchins Rob , Bertucci Marco
Published: July 2007

Liver surgery has always been associated with blood loss, and the problem of bleeding, transfusions, and associated morbidity is a significant one. We present our experience using the TissueLink™ radiofrequency-assisted dissector for parenchymal division during hepatectomy. The TissueLink precoagulates liver parenchyma and allows for dissection of intrahepatic structures, allowing for near bloodless hepatectomy. We have demonstrated our results in terms of morbidity, mortality, blood loss and need for transfusion, and find that they are comparable with results from high-volume HPB centres. The TissueLink is an acceptable tool for use in hepatic transection and may result in less blood loss and lower transfusion rates than conventional methods of transection.
A Differential Association of ALOX15 Polymorphisms with Bone Mineral Density in Pre- and Post-Menopausal Women
Authors: Cheung Ching-Lung , Chan Vivian , Kung Annie W.C.
Published: July 2007

Objective: The 12/15-lipoxygenase gene ALOX15 is reported to be a negative regulator of BMD in knockout mice. Nonetheless results are controversial as over-expression of ALOX15 protects against inflammation-related bone loss. The aim of the present study is to systematically study the relation of ALOX15 polymorphisms in BMD variation in southern Chinese women. Methods: Ten tag single nucleotide polymorphisms (SNP) were genotyped in 942 subjects with either low BMD (defined by a BMD Z score ≤–1.28 at either the hip or spine) or high BMD (Z score ≧+1). Single locus and haplotype associations were performed using logistic regression with adjustment of age, height and weight. Results: The variant ‘G’ allele of rs2619112 was associated with a reduced risk of low BMD at the femoral neck in pre-menopausal women (OR = 0.442, p = 0.007) but an increased risk in post-menopausal women (OR = 1.727, p = 0.042). Haplotype analysis revealed findings similar to the single locus tests. Conclusion: The variant alleles of rs2619112 and rs916055 and their haplotypes of ALOX15 are associated with high BMD in pre-menopausal women but low BMD in post-menopausal women. This suggests that ALOX15 is a dual modulator of BMD variation with opposing effects in pre- and post-menopausal women.
Increased Translocator Protein (TSPO) mRNA Levels in Colon but Not in Rectum Carcinoma
Authors: Königsrainer I. , Vogel U.F. , Beckert S. , Sotlar K. , Coerper S. , Braun A. , Lembert N. , Steurer W. , Königsrainer A. , Kupka S.
Published: July 2007

Background: The peripheral-type benzodiazepine receptor or translocator protein (TSPO) is an 18-kDa protein involved in cell proliferation and apoptosis. TSPO was shown to be overexpressed in malignant tumors and cancer cell lines, correlating with enhanced malignant behavior. The present study analyzed the role of TSPO in patients with colorectal carcinomas. Methods: Tumor tissues and corresponding normal mucosa from 55 patients who underwent resection for colorectal carcinomas were analyzed for TSPO expression in correlation to GAPDH expression(glyceraldehyde-3-phosphate dehydrogenase) using a multiplex RT-PCR assay. Results: TSPO was overexpressed in 67% of the tumors in comparison to corresponding normal mucosa, and positivity as well as expression levels in colon carcinomas were significantly higher than in the rectum carcinomas. In contrast, TSPO expression was not different in intermediate versus high-grade tumors or in lymph node-positive versus -negative patients. Conclusion: The differences in TSPO expression between colon and rectum carcinoma may imply that these tumors are of different biological behavior.
Nitrotyrosine in Human Neonatal Spinal Cord after Perinatal Asphyxia
Authors: Groenendaal Floris , Vles Johannes , Lammers Harry , De Vente Jan , Smit Diane , Nikkels Peter G.J.
Published: July 2007

Background: Spinal cord injury has been reported after perinatal asphyxia in full-term neonates. Objectives: To examine the role of excessive nitric oxide production in perinatal spinal cord injury. Subjects and Methods: Tissue samples of 18 full-term neonates who died of hypoxic-ischemic encephalopathy were analyzed for the presence of nitrotyrosine (NT). Results: NT was demonstrated in 5 of these 18 neonates. In addition, activated caspase 3, a marker of apoptosis, and CD68, as a marker of inflammation, could be demonstrated in some infants. Conclusions: excessive nitric oxide production and subsequent NT formation is seen in spinal cord tissue after severe perinatal asphyxia. This finding may be relevant for the development of neuroprotective strategies.
p53 Mutation Analysis of Low-Grade Dysplasia and High-Grade Dysplasia/Carcinoma in situ of the Esophagus Using Laser Capture Microdissection
Authors: Kobayashi Maki , Kawachi Hiroshi , Takizawa Toichiro , Uchida Keisuke , Sekine Masaki , Kumagai Jiro , Momma Kumiko , Nemoto Tetsuo , Akashi Takumi , Funata Nobuaki , Eishi Yoshinobu , Koike Morio
Published: July 2007

Objectives: The aim of this study was to determine the prevalence and to analyze the characteristics of p53 point mutation in esophageal intraepithelial lesions. Methods: p53 immunohistochemical and genetic analyses were performed on histopathologically and morphometrically diagnosed lesions. Laser capture microdissection samples were used for increased accuracy. Results: Of the 70 lesions studied, 21 were high-grade dysplasia/carcinoma in situ (HGD/CIS), 21 low-grade dysplasia (LGD), 16 reactive atypical epithelia (RAE) and 12 normal epithelia (NE).Immunohistochemical staining showed p53 protein accumulation in 86% (18/21) of HGD/CIS, 81% (17/21) of LGD, and in none of RAE and NE. p53 point mutation was detected in 71% (15/21) of HGD/CIS, 67% (14/21) of LGD, but in none of RAE and NE. Of HGD/CIS and LGD with p53 protein accumulation, similar percentages had mutations: 83% (15/18) and 82% (14/17), respectively. Of lesions with mutations, 72% (21/29) had mutations at hot spots such as codons 238, 248, 273 and 282. Conclusions: p53 point mutation prevalent in HGD/CIS was also present in a large number of LGD. This is strong evidence that LGD is a neoplastic lesion and that p53 point mutation is deeply involved in esophageal carcinogenesis.
Resistance to Fas-Induced Apoptosis in Cells from Human Atherosclerotic Lesions: Elevated Bcl-XL Inhibits Apoptosis and Caspase Activation
Authors: Yang Zhaoqing , Gagarin Dmitry , Ramezani Ali , Hawley Robert G. , McCaffrey Timothy A.
Published: July 2007

The inappropriate survival of cells in the neointima contributes to atherosclerotic plaque progression, while apoptosis in the fibrous cap of lesions contributes to myocardial infarction and stroke. Prior genomic-scale transcript profiling of human carotid artery plaque cells with known sensitivity or resistance to fas-induced apoptosis identified candidate genes involved in lesion cell apoptosis. Retroviral overexpression indicated that several candidate factors were not causative, but that Bcl-XL conferred complete resistance to apoptosis induced by fas ligation. Resistant cells failed to efficiently activate caspase 8, an effect which was also observed in Bcl-XL-transfected cells. Small-molecule Bcl-2/XL inhibitors and siRNA knockdown of Bcl-XL markedly sensitized resistant cells to apoptosis, and partially restored caspase 8 activation. Caspase 3, 6 and 9 inhibitors reduced caspase 8 activation and blocked apoptosis. Complete knockdown of caspase 9 did not reduce apoptosis, while knockdown of Bid suppressed apoptosis, suggesting that mitochondrial pathways independent of caspase 9, such as Smac/Diablo or AIF, provide a necessary mitochondrial input to efficient caspase activation. Bcl-XL appears to modulate lesion cell apoptosis by suppressing mitochondrial amplification of caspase activation loops. The results may have direct implications for controlling plaque instability/progression, and identify a new class of small molecules to inhibit restenosis.
Fragmented Selves: Temporality and Identity in Borderline Personality Disorder
Authors: Fuchs Thomas
Published: July 2007

The concept of narrative identity implies a continuity of the personal past, present and future. This concept is essentially based on the capacity of persons to integrate contradictory aspects and tendencies into a coherent, overarching sense and view of themselves. In ‘mature’ neurotic disorders, this is only possible at the price of repression of important wishes and possibilities for personal development. Patients with borderline personality disorder lack the capacity to establish a coherent self-concept. Instead, they adopt what could be called a ‘post-modernist’ stance towards their life, switching from one present to the next and being totally identified with their present state of affect. Instead of repression, their means of defence consists in a temporal splitting of the self that excludes past and future as dimensions of object constancy, bonding, commitment, responsibility and guilt. The temporal fragmentation of the self avoids the necessity of tolerating the threatening ambiguity and uncertainty of interpersonal relationships. The price, however, consists in a chronic feeling of inner emptiness caused by the inability to integrate past and future into the present and thus to establish a coherent sense of identity. The paper outlines the concept of narrative identity and explores its disturbances in borderline personality disorder. Finally, the increasing prevalence of these disorders is linked to the development of a mainly externally driven, fragmented character in post-modern society.
Disease Variables and Depression Affecting the Process of Coping in Families with a Somatically Ill Parent
Authors: Steck B. , Grether A. , Amsler F. , Schwald Dillier A. , Romer G. , Kappos L. , Bürgin D.
Published: July 2007

Aim and Methods: Based on the investigation of 134 families with a seriously ill parent and 214 offspring, we compared – by means of semistructured psychiatric interviews – the capacity of the ill and the healthy parent and their children to cope with various diseases. We evaluated how disease characteristics such as duration and severity of the disease (assessed by the Karnofsky Index) and associated depression [measured by the Beck Depression Inventory for parents and the Depression Inventory for Children and Adolescents (Depressions-Inventar für Kinder und Jugendliche) for children] influence the coping capacity of all family members. Results: The coping capacity of patients with organic disease (cancer, multiple sclerosis, other somatic diseases) is significantly higher than that of patients with somatization disorder, whereas the depression score of patients with organic disease is significantly lower than that of patients with somatization disorders. The depression of the patient negatively influences his/her coping capacity. Children’s coping capacity does not differ with respect to the parental illness and is not influenced by their own depression. There are significant correlations between the coping capacity of children and their healthy and ill parents affected by organic disease (multiple sclerosis, other somatic diseases, cancer), but not between children and healthy and ill parents with somatization disorders. Multivariate regression analysis shows the mutual influence of coping capacities between the parental couple as well as between the parents and their children. The better the patient (partner) is able to cope with a severe disease, the higher are the values of the coping capacity of the partner (patient). Children older than 6 years with a severely ill, nondepressed and well-coping parent cope well. These results do not apply to parents with somatization disorders. Conclusions: Patients with organic disease cope better and are less depressed, whereas patients with somatization disorders have a lower coping capacity and a higher depression score. Children older than six years cope better. Comprehensive care of a patient with a severe illness has to include his/her family in order to evaluate coping capacities of all family members, particularly of small children, and to assess and treat associated parental depression.
Lack of Association between the BDNF Gene Val66Met Polymorphism and Alzheimer Disease in a Chinese Han Population
Authors: He Xiao-ming , Zhang Zhen-xin , Zhang Jun-wu , Zhou Yong-tao , Tang Mou-ni , Wu Cheng-bin , Hong Zhen
Published: July 2007

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by excessive neuronal loss in specific regions of the brain. Among the areas most severely affected are the basal forebrain cholinergic neurons and their projection regions, the hippocampus and the cortex. Several lines of evidence have made brain-derived neurotrophic factor (BDNF) an important candidate gene conferring risk for AD. Recently, several reports investigated the association between a single nucleotide polymorphism (Val66Met, rs6265) of the BDNF gene and AD but yielded ambiguous results. To figure out the association of this single nucleotide polymorphism in the BDNF gene with sporadic AD in a Chinese Han population, we analyzed 513 patients with AD and 575 controls for the genetic association studies. Our results indicated that the distribution of the BDNF genotypes and alleles did not differ significantly. Similar results were observed when the AD and control groups were stratified by age/age at onset and sex. Our data also showed that in the Chinese Han population, the frequencies of the BDNF Met allele (46.5%) and Val allele (53.5%) were significantly different from ethnic groups from Italy, Japan and the USA. The present data revealed no significant effect of the genotypes on the age at onset for developing AD, and no significant association between the genotypes and the severity of the disease.
Dopamine Transporter Density in the Basal Ganglia in Obsessive-Compulsive Disorder, Measured with [123I]IPT SPECT before and after Treatment with Serotonin Reuptake Inhibitors
Authors: Kim C.H. , Cheon K.A. , Koo M.-S. , Ryu Y.H. , Lee J.D. , Chang J.W. , Lee H.S.
Published: July 2007

It has been suggested that dopamine as well as serotonin are associated with the pathophysiology of obsessive-compulsive disorder (OCD). 5-Hydroxytryptophan inhibits dopamine release in healthy persons as well as in patients with OCD, and serotonin tonic inhibition affects dopamine function in basal ganglia, indicating a close relationship between serotonin and the dopamine system. Using iodine-123-labeled N-(3-iodopropen-2-yl)-2β-carbomethoxy-3β-(4-chlorophenyl) tropane ([123I]IPT) single photon emission computed tomography (SPECT), we investigated the dopamine transporter (DAT) density in the basal ganglia of patients with OCD. The test consists of two measurements before and after treatment with serotonin reuptake inhibitors (SRIs). Ten patients with OCD before and after treatment with SRIs were included. We performed brain SPECT 2 h after intravenous administration of [123I]IPT using a dual-head SPECT camera (Vertex, ADAC, Calif., USA) and analyzed the SPECT data, reconstructed for the assessment of the specific/nonspecific DAT binding ratio in the basal ganglia. We then examined the correlation between the scores of OCD symptom changes, assessed with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), and DAT binding ratio. Patients with OCD after treatment with SRIs showed a significantly decreased DAT binding ratio in the right basal ganglia compared with baseline. A significant correlation was found between the total scores and compulsion score changes of the Y-BOCS and the changes of the DAT binding ratio of the right basal ganglia. These findings suggest that the dopaminergic neurotransmitter system of the basal ganglia could play an important role in the symptom improvement of OCD patients.
Increased Incidence of Pituitary Microadenomas in Suicide Victims
Authors: Furgal-Borzych Alicja , Lis Grzegorz J. , Litwin Jan A. , Rzepecka-Wozniak Ewa , Trela Franciszek , Cichocki Tadeusz
Published: July 2007

Background: Current data suggest an influence of the hypothalamic-pituitary-adrenal axis on suicidal behavior. The frequency of pituitary adenomas in suicide victims has not yet been investigated. Objectives: The aim of this study was to assess whether the incidence of pituitary adenomas is correlated with suicide. Methods: Serial sections of 151 human pituitary glands obtained upon autopsy were examined microscopically. The glands were collected from 70 suicide victims and 81 subjects whose deaths were classified as unexpected or accidental (nonsuicidal group). The sections were stained with hematoxylin-eosin and the presence of adenoma was confirmed by immunostaining for collagen III. Results: In the suicidal group, pituitary microadenomas were found in 32 cases (47.7%), while in the nonsuicidal group microadenomas were detected in 15 cases (18.3%). The observed difference was statistically significant (p = 0.0003). The relative risk ratio of suicide in persons with pituitary adenomas was estimated at 1.9. Logistic regression analysis in a model controlled for age and sex showed that microadenomas constituted a unique risk factor in this model. The immunohistochemical phenotyping revealed a higher percentage of immunopositive (secreting) microadenomas in the nonsuicidal group as compared to the suicidal group (80.0 vs. 59.38%) and a predominance of growth hormone-secreting microadenomas in both groups. However, these differences as well as differences in the hormonal profiles of microadenomas between the groups were not significant. Conclusions: These results suggest that pituitary adenomas belong to suicide risk factors.
A Preliminary Study of Dopamine Transporter Binding in Bipolar and Unipolar Depressed Patients and Healthy Controls
Authors: Amsterdam Jay D. , Newberg Andrew B.
Published: July 2007

Objective: We examined striatal dopamine transporter (DAT) binding in bipolar and unipolar depressed patients and compared these values to those obtained from healthy control subjects using the selective DAT radioligand [99mTc]TRODAT-1 and single photon emission computed tomography imaging. We hypothesized that DAT levels might be higher in bipolar versus unipolar patients. Methods: [99mTc]TRODAT-1 scans were acquired from 5 bipolar and 10 unipolar patients and from 46 healthy controls. Distribution volume ratio (DVR) of [99mTc]TRODAT-1 binding affinity was calculated for regions of interest in the striatum. Results: Bipolar patients had greater DVR values compared to controls in the right posterior putamen (p = 0.001) and in the left caudate region (p = 0.007). Bipolar patients had modestly lower DAT binding in all brain regions examined, and a significantly lower DVR in the right caudate region compared to unipolar patients (p = 0.05). Conclusion: These data suggest that striatal DAT density may be increased in bipolar and unipolar depressed patients compared to controls, and that bipolar and unipolar depressed patients may have a different pattern of striatal DAT binding.
An Alternative Diagnostic Test for Active Ménière’s Disease and Cochlear Hydrops Using High-Pass Noise Masked Responses: The Complex Amplitude Ratio
Authors: Don Manuel , Kwong Betty , Tanaka Chiemi
Published: July 2007

We [Don et al.: Otol Neurotol 2005;26:711–722] previously demonstrated that patients diagnosed with an active case of Ménière’s disease could be distinguished from non-Ménière’s normal-hearing subjects by a special auditory brainstem response method involving clicks and ipsilateral high-pass masking pink noise. Specifically, auditory brainstem responses to clicks presented alone and clicks with masking noise high-pass filtered at 8, 4, 2, 1 and 0.5 kHz were recorded. It was shown that the level of masking noise sufficient to progressively mask the response to clicks in non-Ménière’s normal-hearing subjects was insufficient to appropriately mask the responses in Ménière’s disease subjects, resulting in an obvious undermasked component. A relative latency measure of wave V or the undermasked component in the response to clicks with 0.5 kHz high-pass masking noise and wave V in the response to clicks presented alone clearly distinguished these two groups on an individual level, thus making it a valuable clinical tool. However, determining the peak latency of wave V or the undermasked component can be difficult in some cases. In anticipation of this difficulty, we investigated and present in this paper several amplitude measures that may help in the evaluation of these cases. One amplitude measure, the ‘complex amplitude ratio’, appears to be a good alternative when the latency measure of the undermasked component is difficult to determine.
Activation in Primary Auditory Cortex during Silent Lipreading Is Determined by Sex
Authors: Ruytjens Liesbet , Albers Frans , van Dijk Pim , Wit Hero , Willemsen Antoon
Published: July 2007

Recent studies investigating whether the primary auditory cortex (PAC) is involved in silent lipreading gave inconsistent results. We used positron emission tomography to identify which areas in the temporal lobe process visible speech, with a focus on the PAC. Subjects were tested on lipreading numbers and only the best lipreaders were included in the study (n = 18; 9 female, 9 male). Each subject was scanned while either watching a movie with a speaker silently articulating numbers (lipreading condition) or watching a static image of the same speaker (baseline condition). Subjects were instructed to repeat internally the number seen or the number ‘1’. Compared to the baseline condition, silent lipreading activated temporal areas in both hemispheres with the largest activation clusters in the left hemisphere. When the whole group was examined, no activation in the PAC was found. But when investigating the two sexes separately, the female group demonstrated activation of the left PAC. There was no significant activation in the right female PAC or in the left and right male PAC. Since both groups had similar performances in lipreading, differential activity in the PAC has no effect on lipreading scores. These results may explain previous inconsistent results where no differentiation for sex was made.