bluuebunny/crossref_metadata_2025 huggingface dataset:
Classification of Streptomyces griseus (Krainsky 1914) Waksman and Henrici 1948 and related species and the transfer of ‘Microstreptospora cinerea’ to the genus Streptomyces as Streptomyces yanii sp. nov.
Authors: Liu Zhiheng , Shi Yanlin , Zhang Yamei , Zhou Zhihong , Lu Zhitang , Li Wei , Huang Ying , Rodríguez Carlos , Goodfellow Michael
Published: July 2005

A soil actinomycete, strain 80-133T, with the non-validly published name ‘Microstreptospora cinerea’, was the subject of a polyphasic study designed to clarify its taxonomic status. Comparative 16S rRNA gene sequence studies indicated that the organism belonged to the genusStreptomyces, a result in line with previous chemotaxonomic and morphological data. The strain belonged to theStreptomyces griseusclade, but could be distinguished from representatives of species assigned to this taxon by using DNA–DNA relatedness and phenotypic data. In light of these findings, it is proposed that the organism should be recognized as a novel species of the genusStreptomyces. The name proposed for this taxon isStreptomyces yaniisp. nov., with isolate 80-133T(=AS 4.1146T=JCM 3331T) as the type strain. It was also shown that representative strains ofStreptomyces argenteolus,Streptomyces caviscabies,S. griseusandStreptomyces setoniibelong to the same genomic species and have key phenotypic properties in common. It is proposed thatS. caviscabiesandS. setoniishould be considered as later heterotypic synonyms ofS. griseusand thatS. argenteolusAS 4.1693Tshould also be assigned to this taxon.
Winogradskyella poriferorum sp. nov., a novel member of the family Flavobacteriaceae isolated from a sponge in the Bahamas
Authors: Lau Stanley C. K. , Tsoi Mandy M. Y. , Li Xiancui , Plakhotnikova Ioulia , Dobretsov Sergey , Lau Ken W. K. , Wu Madeline , Wong Po-Keung , Pawlik Joseph R. , Qian Pei-Yuan
Published: July 2005

A Gram-negative, rod-shaped bacterium (designated strain UST030701-295T) with fast gliding motility was isolated from the surface of the sponge Lissodendoryx isodictyalis in the Bahamas. Colonies of UST030701-295T were yellow in colour, 2–4 mm in diameter, convex with a smooth surface and entire margins. UST030701-295T was heterotrophic, strictly aerobic and required NaCl for growth (1·0–4·0 %). Growth was observed at pH 6·0–10·0 and at 12–44 °C. Phylogenetic analysis of the 16S rRNA gene sequence placed UST030701-295T within the genus Winogradskyella of the family Flavobacteriaceae, sharing 94·7–95·8 % similarity with the three recognized members of the genus. The G+C content of the DNA was 32·8 mol% and the predominant fatty acids were iso-C15 : 1, iso-C15 : 0, iso-C15 : 0 2-OH, iso-C15 : 0 3-OH, iso-C16 : 0 3-OH, C16 : 1
ω7 and iso-C17 : 0 3-OH (together representing 75·4 % of the total); these data supported the affiliation of UST030701-295T to the genus Winogradskyella. UST030701-295T differed from the three recognized species of Winogradskyella in 7–17 traits. Molecular evidence together with phenotypic characteristics suggests that UST030701-295T represents a novel species within the genus Winogradskyella, for which the name Winogradskyella poriferorum sp. nov. is proposed. The type strain is UST030701-295T (=NRRL B-41101T=JCM 12885T).
Dyella koreensis sp. nov., a β-glucosidase-producing bacterium
Authors: An Dong-Shan , Im Wan-Taek , Yang Hee-Chan , Yang Deok-Chun , Lee Sung-Taik
Published: July 2005

A bacterial strain (designated BB4T), which has β-glucosidase activity, was isolated from soil around the roots of bamboo plants. Cells were Gram-negative, aerobic, non-motile and straight-rod-shaped. Phylogenetic analysis of 16S rRNA gene sequences revealed a clear affiliation with members of the family ‘Xanthomonadaceae’. The 16S rRNA gene sequence of strain BB4T showed the following sequence similarities: 97·7 % to Dyella japonica XD53T, 97·1 % to Frateuria aurantia LMG 1558T, 96·2 % to Fulvimonas soli LMG 19981T, 94·3 % to Rhodanobacter lindaniclasticus RP5575T and <90 % to other members of the ‘Gammaproteobacteria’. The G+C content of the genomic DNA was 63·8 mol%. The major fatty acids were branched forms, especially large proportions of iso-C15 : 0, iso-C17 : 0 and iso-C17 : 1
ω9c, similar to the profile of the genus Dyella. The results of DNA–DNA hybridization with D. japonica XD53T and Frateuria aurantia LMG 1558T, in combination with phenotypic characteristics and 16S rRNA gene sequence analysis, demonstrated that strain BB4T should be classified as a novel Dyella species. The name Dyella koreensis sp. nov. is proposed, with strain BB4T (=KCTC 12359T=NBRC 100831T) as the type strain.
Cellulomonas terrae sp. nov., a cellulolytic and xylanolytic bacterium isolated from soil
Authors: An Dong-Shan , Im Wan-Taek , Yang Hee-Chan , Kang Myung Suk , Kim Kwang Kyu , Jin Long , Kim Myung Kyum , Lee Sung-Taik
Published: July 2005

A bacterial strain (DB5T), with polysaccharide-degrading activities, was isolated from garden soil in Daejeon, Republic of Korea. The cells were Gram-positive, aerobic or facultatively anaerobic, non-motile straight rods. Phylogenetic analysis based on 16S rRNA gene sequences showed that this strain belongs to the genusCellulomonasand that it is most closely related toCellulomonas xylanilyticaLMG 21723TandCellulomonas humilataATCC 25174T(98·0 and 97·9 % similarity, respectively). Chemotaxonomic data also supported the classification of strain DB5Tin the genusCellulomonas, i.e.l-ornithine as the cell-wall diamino acid, anteiso-C15 : 0and iso-C15 : 0as the major fatty acids, MK-9(H4) as the predominant menaquinone and the presence of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol and phosphatidylinositol mannosides in the polar lipid profile. The results of DNA–DNA hybridization in combination with chemotaxonomic and physiological data demonstrated that strain DB5T(=KCTC 19081T=NBRC 100819T) should be classified as the type strain of a novel species within the genusCellulomonas, for which the nameCellulomonas terraesp. nov. is proposed.
Engineering Cytoplasmic Male Sterility via the Chloroplast Genome by Expression of β-Ketothiolase
Authors: Ruiz Oscar N. , Daniell Henry
Published: July 2005

While investigating expression of the polydroxybutyrate pathway in transgenic chloroplasts, we addressed the specific role of β-ketothiolase. Therefore, we expressed the phaA gene via the chloroplast genome. Prior attempts to express the phaA gene in transgenic plants were unsuccessful. We studied the effect of light regulation of the phaA gene using the psbA promoter and 5′ untranslated region, and evaluated expression under different photoperiods. Stable transgene integration into the chloroplast genome and homoplasmy were confirmed by Southern analysis. The phaA gene was efficiently transcribed in all tissue types examined, including leaves, flowers, and anthers. Coomassie-stained gel and western blots confirmed hyperexpression of β-ketothiolase in leaves and anthers, with proportionately high levels of enzyme activity. The transgenic lines were normal except for the male-sterile phenotype, lacking pollen. Scanning electron microscopy revealed a collapsed morphology of the pollen grains. Floral developmental studies revealed that transgenic lines showed an accelerated pattern of anther development, affecting their maturation, and resulted in aberrant tissue patterns. Abnormal thickening of the outer wall, enlarged endothecium, and vacuolation affected pollen grains and resulted in the irregular shape or collapsed phenotype. Reversibility of the male-sterile phenotype was observed under continuous illumination, resulting in viable pollen and copious amount of seeds. This study results in the first engineered cytoplasmic male-sterility system in plants, offers a new tool for transgene containment for both nuclear and organelle genomes, and provides an expedient mechanism for F1 hybrid seed production.
Complex Organization and Evolution of the Tomato Pericentromeric Region at the FER Gene Locus
Authors: Guyot Romain , Cheng Xudong , Su Yan , Cheng Zhukuan , Schlagenhauf Edith , Keller Beat , Ling Hong-Qing
Published: July 2005

Tomato (Lycopersicon esculentum) is a model species for molecular biology research and a candidate for large-scale genome sequencing. Pericentromeric heterochromatin constitutes a large portion of the tomato chromosomes. However, the knowledge of the structure, organization, and evolution of such regions remains very limited. Here, we report the analysis of a 198-kb sequence near the FER gene, located in a distal part of pericentromeric heterochromatin on the long arm of tomato chromosome 6. Nine genes, one pseudogene, and 55 transposable elements (TEs) were identified, showing a low gene density (19.8 kb/gene) and a high content of transposable elements (>45% of the sequence). Six genes (56B23_g3, g5, g7, g8, g9, and g10) have perfect matches (>98% identity) with tomato expressed sequence tags. Two genes (56B23_g1 and g6), which share <98% sequence identity with expressed sequence tags, were confirmed for transcriptional activity by reverse transcription-PCR. The genes were not uniformly distributed along the sequence and grouped into gene islands separated by stretches of retrotransposons, forming a pattern similar to that found in the gene-rich regions of the large genomes of maize (Zea mays) and Triticeae. Long terminal repeat retrotransposons account for 60% of the TE sequence length. Sixteen of 55 TEs were completely new and remain unclassified. Surprisingly, five of the seven identified DNA transposons were closely associated with coding regions. The action of transposable elements and DNA rearrangements form the molecular basis of the dynamic genome evolution at the FER locus. Multiple rounds of genome duplication in Arabidopsis (Arabidopsis thaliana) and subsequent gene loss have generated a mosaic pattern of conservation between tomato and Arabidopsis orthologous sequences. Our data show that the distal parts of pericentromeric heterochromatin may contain many valuable genes and that these regions form an evolutionary active part of the tomato genome.
It's All GO for Plant Scientists
Authors: Clark Jennifer I. , Brooksbank Cath , Lomax Jane
Published: July 2005

The Gene Ontology project (http://www.geneontology.org/) produces structured, controlled vocabularies and gene product annotations. Gene products are classified according to the cellular locations and biological process in which they act, and the molecular functions that they carry out. We annotate gene products from a broad range of model species and provide support for those groups that wish to contribute annotation of further model species. The Gene Ontology facilitates the exchange of information between groups of scientists studying similar processes in different model organisms, and so provides a broad range of opportunities for plant scientists.
Plant Genome Resources at the National Center for Biotechnology Information
Authors: Wheeler David L. , Smith-White Brian , Chetvernin Vyacheslav , Resenchuk Sergei , Dombrowski Susan M. , Pechous Steven W. , Tatusova Tatiana , Ostell James
Published: July 2005

The National Center for Biotechnology Information (NCBI) integrates data from more than 20 biological databases through a flexible search and retrieval system called Entrez. A core Entrez database, Entrez Nucleotide, includes GenBank and is tightly linked to the NCBI Taxonomy database, the Entrez Protein database, and the scientific literature in PubMed. A suite of more specialized databases for genomes, genes, gene families, gene expression, gene variation, and protein domains dovetails with the core databases to make Entrez a powerful system for genomic research. Linked to the full range of Entrez databases is the NCBI Map Viewer, which displays aligned genetic, physical, and sequence maps for eukaryotic genomes including those of many plants. A specialized plant query page allow maps from all plant genomes covered by the Map Viewer to be searched in tandem to produce a display of aligned maps from several species. PlantBLAST searches against the sequences shown in the Map Viewer allow BLAST alignments to be viewed within a genomic context. In addition, precomputed sequence similarities, such as those for proteins offered by BLAST Link, enable fluid navigation from unannotated to annotated sequences, quickening the pace of discovery. NCBI Web pages for plants, such as Plant Genome Central, complete the system by providing centralized access to NCBI's genomic resources as well as links to organism-specific Web pages beyond NCBI.
Extension of the Visualization Tool MapMan to Allow Statistical Analysis of Arrays, Display of Coresponding Genes, and Comparison with Known Responses
Authors: Usadel Björn , Nagel Axel , Thimm Oliver , Redestig Henning , Blaesing Oliver E. , Palacios-Rojas Natalia , Selbig Joachim , Hannemann Jan , Piques Maria Conceição , Steinhauser Dirk , Scheible Wolf-Rüdiger , Gibon Yves , Morcuende Rosa , Weicht Daniel , Meyer Svenja , Stitt Mark
Published: July 2005

MapMan is a user-driven tool that displays large genomics datasets onto diagrams of metabolic pathways or other processes. Here, we present new developments, including improvements of the gene assignments and the user interface, a strategy to visualize multilayered datasets, the incorporation of statistics packages, and extensions of the software to incorporate more biological information including visualization of coresponding genes and horizontal searches for similar global responses across large numbers of arrays.
KaPPA-View. A Web-Based Analysis Tool for Integration of Transcript and Metabolite Data on Plant Metabolic Pathway Maps
Authors: Tokimatsu Toshiaki , Sakurai Nozomu , Suzuki Hideyuki , Ohta Hiroyuki , Nishitani Kazuhiko , Koyama Tanetoshi , Umezawa Toshiaki , Misawa Norihiko , Saito Kazuki , Shibata Daisuke
Published: July 2005

The application of DNA array technology and chromatographic separation techniques coupled with mass spectrometry to transcriptomic and metabolomic analyses in plants has resulted in the generation of considerable quantitative data related to transcription and metabolism. The integration of “omic” data is one of the major concerns associated with research into identifying gene function. Thus, we developed a Web-based tool, KaPPA-View, for representing quantitative data for individual transcripts and/or metabolites on plant metabolic pathway maps. We prepared a set of comprehensive metabolic pathway maps for Arabidopsis (Arabidopsis thaliana) and depicted these graphically in Scalable Vector Graphics format. Individual transcripts assigned to a reaction are represented symbolically together with the symbols of the reaction and metabolites on metabolic pathway maps. Using quantitative values for transcripts and/or metabolites submitted by the user as Comma Separated Value-formatted text through the Internet, the KaPPA-View server inserts colored symbols corresponding to a defined metabolic process at that site on the maps and returns them to the user's browser. The server also provides information on transcripts and metabolites in pop-up windows. To demonstrate the process, we describe the dataset obtained for transgenic plants that overexpress the PAP1 gene encoding a MYB transcription factor on metabolic pathway maps. The presentation of data in this manner is useful for viewing metabolic data in a way that facilitates the discussion of gene function.
Serial Analysis of Gene Expression Study of a Hybrid Rice Strain (LYP9) and Its Parental Cultivars
Authors: Bao JingYue , Lee Sanggyu , Chen Chen , Zhang XiuQing , Zhang Yu , Liu SiQi , Clark Terry , Wang Jian , Cao MengLiang , Yang HuanMing , Wang San Ming , Yu Jun
Published: July 2005

Using the serial analysis of gene expression technique, we surveyed transcriptomes of three major tissues (panicles, leaves, and roots) of a super-hybrid rice (Oryza sativa) strain, LYP9, in comparison to its parental cultivars, 93-11 (indica) and PA64s (japonica). We acquired 465,679 tags from the serial analysis of gene expression libraries, which were consolidated into 68,483 unique tags. Focusing our initial functional analyses on a subset of the data that are supported by full-length cDNAs and the tags (genes) differentially expressed in the hybrid at a significant level (P < 0.01), we identified 595 up-regulated (22 tags in panicles, 228 in leaves, and 345 in roots) and 25 down-regulated (seven tags in panicles, 15 in leaves, and three in roots) in LYP9. Most of the tag-identified and up-regulated genes were found related to enhancing carbon- and nitrogen-assimilation, including photosynthesis in leaves, nitrogen uptake in roots, and rapid growth in both roots and panicles. Among the down-regulated genes in LYP9, there is an essential enzyme in photorespiration, alanine:glyoxylate aminotransferase 1. Our study adds a new set of data crucial for the understanding of molecular mechanisms of heterosis and gene regulation networks of the cultivated rice.
Relationship between symptoms and hypersensitivity to rectal distension in patients with irritable bowel syndrome
Authors: KUIKEN S. D. , LINDEBOOM R. , TYTGAT G. N. , BOECKXSTAENS G. E.
Published: July 2005

Background:  Visceral hypersensitivity is considered an important pathophysiological mechanism in irritable bowel syndrome, yet its relationship to symptoms is unclear.

Aim:  To detect possible associations between symptoms and the presence of hypersensitivity to rectal distension in patients with irritable bowel syndrome.

Methods:  Ninety‐two irritable bowel syndrome patients and 17 healthy volunteers underwent a rectal barostat study. The association between specific irritable bowel syndrome symptoms and the presence of hypersensitivity was examined using Area under the Receiver Operating Characteristic curves.

Results:  Irritable bowel syndrome patients had significantly lower thresholds for discomfort/pain than healthy volunteers: 24 (18–30) and 30 (27–45) mmHg above minimal distending pressure, respectively. Forty‐one patients (45%) showed hypersensitivity to rectal distension. Proportions of patients with different predominant bowel habits were similar in hypersensitive and normosensitive subgroups (diarrhoea predominant: 39 and 41%, respectively; alternating type: 27 and 28%, respectively; constipation predominant: 34 and 31%, respectively). Severe abdominal pain was more frequent in hypersensitive, compared with normosensitive patients (88% vs. 67%, P = 0.02), but none of the individual irritable bowel syndrome symptoms could accurately predict the presence of hypersensitivity, as assessed by Area under the Receiver Operating Characteristic curve analysis.

Conclusions:  Hypersensitive and normosensitive irritable bowel syndrome patients present with comparable, heterogeneous symptomatology. Therefore, selection based on clinical parameters is unlikely to discriminate individual irritable bowel syndrome patients with visceral hypersensitivity from those with normal visceral sensitivity.
Systematic review: proton‐pump inhibitor failure in gastro‐oesophageal reflux disease – where next?
Authors: FASS R. , SHAPIRO M. , DEKEL R. , SEWELL J.
Published: July 2005

Proton‐pump inhibitor failure has become a common clinical dilemma in gastrointestinal clinics and has been increasingly encountered at the primary care level as well. Underlying mechanisms are diverse and may overlap. Most patients who have proton‐pump inhibitor failure are likely to originate from the non‐erosive reflux disease phenotype. Currently, available diagnostic modalities provide limited clues to the exact underlying cause. Treatment relies primarily on escalating dosing of proton‐pump inhibitors. However, new insights into the pathophysiology of proton‐pump inhibitor failure are likely to provide alternative therapeutic options.
The cost‐effectiveness of biomarkers for predicting the development of oesophageal adenocarcinoma
Authors: RUBENSTEIN J. H. , VAKIL N. , INADOMI J. M.
Published: July 2005

Background: The recommended surveillance strategy for oesophageal adenocarcinoma may prevent as few as 50% of cancer deaths. Tissue biomarkers have been proposed to identify high‐risk patients.

Aim: To determine performance characteristics of an ideal biomarker, or panel of biomarkers, that would make its use more cost‐effective than the current surveillance strategy.

Methods: We created a Markov model using data from published literature, and performed a cost‐utility analysis. The population consisted of 50‐year‐old Caucasian men with gastro‐oesophageal reflux, who were monitored until age 80. We examined strategies of observation only, current practice (dysplasia‐guided surveillance), surveillance every 3 months for patients with a positive biomarker (biomarker‐guided surveillance), and oesophagectomy immediately for a positive biomarker (biomarker‐guided oesophagectomy). The primary outcome was the threshold cost and performance characteristics needed for a biomarker to be more cost‐effective than current practice.

Results: Regardless of the cost, the biomarker needs to be at least 95% specific for biomarker‐guided oesophagectomy to be cost‐effective. For biomarker‐guided surveillance to be cost‐effective, a $100 biomarker could be 80% sensitive and specific.

Conclusions: Biomarkers predicting the development of oesophageal adenocarcinoma would need to be fairly accurate and inexpensive to be cost‐effective. These results should guide the development of biomarkers for oesophageal adenocarcinoma.
Living donor liver transplantation for hepatitis C related hepatocellular carcinoma in a haemophilia A patient
Authors: Au W. Y. , Liu C. L. , Lo C. M. , Fan S. T. , Lam C. K.
Published: July 2005

Summary.  We report the first case of unrelated living liver transplantation for hepatitis C related hepatocellular carcinoma (HCC) in a Chinese patient with haemophilia A. The development of cirrhosis and HCC was insidious in this patient, who has previously failed interferon treatment despite low viral load and genotype 6a. With factor VIII and novoseven support, there were no operative complications and there was no need for blood transfusion. Postoperative pegulated interferon treatment resulted in viral clearance with no increased cellular rejection. The use of living donors represent a potential life saving therapeutic options for hepatitis C virus related complications in haemophiliac, especially in countries of organ shortage. Careful patient and donor choice, meticulous surgical expertise and proper counselling, however, are prudent requirements.
Helicobacter pylori infection in patients with haemophilia in Poland: prevalence and risk of upper gastrointestinal bleeding
Authors: Szczepanik A. B. , Zaleska M. , Wiszniewski A. , Wislawski S. , Misiak A. , Maryniak R. , Windyga J.
Published: July 2005

Summary.  Infection with Helicobacter pylori is the main aetiological factor for erosive gastritis and duodenal or gastric peptic ulcers often complicated with life‐threatening bleeding in patients with coagulation disorders. The aim of this prospective study was to evaluate the prevalence of Helicobacter pylori infection in haemophilia patients, and to assess the risk of gastrointestinal bleeding associated with this infection. From 2000 to 2002, 146 patients with haemophilia (129, haemophilia A; 13, haemophilia B), mean age, 39.9 years (±7.3), were investigated for H. pylori infection using IgG and IgA latex serological test. The control group included 100 men with no coagulation disorders, mean age, 40.9 years (±9.2). For 72 (49.3%) patients with haemophilia and 39 controls (39.0%) serological tests were positive indicating the presence of H. pylori infection (P =0.1112). A history of gastrointestinal bleeding was reported in 46 patients (31.5%) with haemophilia and in two control group patients (2.0%) (P < 0.0001). Gastrointestinal bleeding was significantly more frequent in patients with haemophilia infected with H. pylori (33/46; 71.7%) than in patients with no H. pylori infection (13/46; 28.3%; P = 0.0002). In conclusion, the prevalence of H. pylori infection in haemophilic patients in Poland is comparable with that in patients with no coagulation disorders. Helicobacter pylori infection is a risk factor for duodenal and gastric ulcer bleeding in haemophilia patients. In view of the high frequency of upper gastrointestinal bleeding associated with H. pylori infection, we believe that screening and eradication therapy are appropriate in haemophilia patients.
Factor VIII inhibitor associated with peginterferon
Authors: Herman C. , Boggio L. , Green D.
Published: July 2005

Summary.  We present a case of a 53‐year‐old black male who developed a factor VIII inhibitor during his treatment for hepatitis C virus infection with peginterferon. The development of inhibitors against factor VIII during peginterferon therapy has been rarely reported. We have reviewed the current literature and the following case presentation provides the first demonstration, to our knowledge, in which chronic exposure to peginterferon is associated with an acquired factor VIII inhibitor.
Thromboelastography measurements of whole blood from factor VIII‐deficient mice supplemented with rFVIII
Authors: Landskroner K. A. , Olson N. C. , Jesmok G. J.
Published: July 2005

Summary.  The rotational thromboelastography (ROTEG) assay system allows the real‐time analysis of clot formation (fibrin formation) in a whole‐blood assay format. The ROTEG system provides significant advantages over the current plasma‐based assay systems as it includes the important interactions between cellular and plasmatic coagulation factors. We have employed the ROTEG system to characterize clot formation dynamics in factor VIII‐ deficient mouse whole blood and examined the ability of recombinant FVIII (rFVIII) supplementation to restore the normal phenotype. The ability to generate a clear dose–response relationship by adding rFVIII to FVIII‐deficient murine whole blood (FVIII−/−) demonstrates the feasibility of this approach. A dose–response from 1 U to 0.00001 U mL−1 demonstrates the enhanced sensitivity of the ROTEG system. Further characterization of this experimental approach may provide a potential tool for comparing the activity of FVIII concentrates and/or evaluating FVIII mutants.
Thrombin generation and phenotypic correlation in haemophilia A
Authors: Beltrán‐Miranda C. P. , Khan A. , Jaloma‐Cruz A. R. , Laffan M. A.
Published: July 2005

Summary.  The clinical phenotype of patients with haemophilia A (HA) often differs between individuals with the same factor VIII (FVIII) gene defect (e.g. within the same family) or the same coagulant activity of FVIII (FVIII:C). We proposed that because the thrombin generation assay in platelet‐poor plasma of HA patients provides more information [peak thrombin concentration, endogenous thrombin potential (ETP), rate of thrombin generation and lag‐time] than a clot‐based FVIII assay it might provide insight into these differences. We therefore investigated the relation between the results of the thrombin generation assay and the clinical severity in nine families with HA (23 patients with different phenotypes). We also examined the contribution of prothrombotic risk factors: (FV Leiden G1691A and prothrombin G20210A), the coagulant activity of FVIII and tissue factor (5′UTR) polymorphisms. Our data detect marked differences between individuals but these did not correlate with the reported clinical phenotype. These differences were also reflected in a marked difference in response to the therapeutic amounts of FVIII. This might account for differences in amounts of treatment consumption. Reduced peak and possibly rate of thrombin generation, rather than FVIII:C or ETP appear to represent the critical defects in FVIII‐deficient plasma. We suggest that the analysis of parameters in thrombin generation is a useful tool to detect bleeding tendency in HA but not to predict the modulation of the haemorrhagic tendency in patients within families. However the presence of the other factors such as vessel wall components, protein C and platelets might need to be incorporated into this system.
Progression of HIV infection in the post‐HAART era among a cohort of HIV+ Greek haemophilia patients
Authors: Katsarou O. , Touloumi G. , Antoniou A. , Kouramba A. , Hatzakis A. , Karafoulidou A.
Published: July 2005

Summary.  Aim: The study aims to describe the course of HIV‐1 infection in the pre‐ and post‐HAART period in a cohort of HIV+ haemophilia patients followed up for up to 21 years. Methods: The cohort includes 158 haemophilic men with known seroconversion dates followed up prospectively for a median time of 12 and 5.7 years in the pre‐ (1980–96) and post‐HAART period (1997–2003), respectively. Results: The risk of developing AIDS was lowered by 56% in the post‐ as compared to the pre‐HAART period. Of the 158 patients 69 developed AIDS in the pre‐HAART period while of the 59 subjects still alive and AIDS free on 1/1/1997 six developed AIDS. The rate of PCP (12.0 cases per 1000 person‐years) and NHL (5.4 cases per 1000 person‐years), the most common causes of AIDS diagnosis in the pre‐HAART era, were remarkably reduced in the post‐HAART era (both rates: 2.8 cases per 1000 person‐years). On the contrary, the corresponding risk for non‐AIDS deaths was fourfold increased in the post‐HAART period. Of the 38 non‐AIDS related deaths in both periods, 13 occurred post‐HAART. The predominant cause of non‐AIDS mortality in both periods was end‐stage liver disease (ESLD) (7 pre‐ and 4 post‐HAART). The rate of non‐AIDS related cancers was also increased during the post‐HAART period. Conclusion: In this haemophilia cohort the risk of AIDS has substantially reduced in the post‐HAART period, but the rate of non‐AIDS mortality tended to increase. Among haemophilia subjects, due to the high rates of HCV/HIV coinfection, ESLD, the predominant cause of non‐AIDS mortality, will become an increasingly important clinical problem.
Immune tolerance in children with factors VIII and IX inhibitors: a single centre experience
Authors: Mathias M. , Liesner R. , Hann I. , Khair K.
Published: July 2005

Summary.  Alloimmune FVIII and FIX inhibitors are the most serious complication of haemophilia in the postviral contamination era and their optimal management remains controversial. We present 15 boys with severe haemophilia (14 with haemophilia A and 1 with haemophilia B) who have received immune tolerance at our centre over a 9‐year period. Twelve of them (80%) were successfully tolerized with varying dose intensities, but three of them (including the boy with haemophilia B) failed tolerization. The factors, which were associated with successful tolerance in our group, were a low maximum inhibitor titre and a short interval between diagnosis of the inhibitor and the start of immune tolerance. The time taken to achieve immune tolerance varied from 1 to 27 months and none of the inhibitors have recurred. Two of the three boys who failed immune tolerance had had their inhibitor for 72 and 69 months, respectively before tolerance was attempted.
Bone properties and muscle strength of young haemophilia patients
Authors: Falk B. , Portal S. , Tiktinsky R. , Zigel L. , Weinstein Y. , Constantini N. , Kenet G. , Eliakim A. , Martinowitz U.
Published: July 2005

Summary.  Purpose:  To evaluate bone properties, muscle strength and the relationship between the two, in young (7.0–17.7 years) haemophilia patients (h) and healthy boys (c).

Subjects:  Twenty‐seven boys with severe haemophilia and 33 healthy boys, of similar age, body mass, height, (mean ± sd for h and c, respectively: 11.2 ± 3.2 vs. 11.4 ± 2.9 years, 42.6 ± 16.6 vs. 41.6 ± 17.3 kg, 145 ± 18 vs. 146 ± 17 cm) and pubertal stage according to secondary sex characteristics, volunteered for the study. all subjects were physically inactive (as determined by questionnaire).

Methods:  Subjects performed isokinetic elbow and knee extension and flexion tests at two angular velocities (biodex system ii dynamometer). Bone properties were evaluated by qualitative ultrasound (sunlight omnisenseTM), at the distal radius and tibial mid‐shaft. H subjects received prophylactic factor viii treatment within the 24 h preceding testing. No test was performed in the presence of haemorrhage.

Results:  Muscle strength was consistently higher in c compared with h, especially in the lower limbs (e.g. knee extension: 1.80 ± 0.44 vs 1.48 ± 0.53 N·m·kg−1 body mass, respectively, p = 0.01). No differences were observed in tibial or radial speed of sound between groups. Correlations between muscle strength and bone properties were observed only in the lower limbs and only in c (r = 0.37–0.48).

Conclusion:  Muscle strength, especially lower limbs’ strength, was lower in haemophilia patients compared with a matched, similarly inactive population of healthy boys. Nevertheless, at this age range, this relative weakness is not associated with inferior bone properties.
Assessing functional health status in adults with haemophilia: towards a preliminary core set of clinimetric instruments based on a literature search in Rheumatoid Arthritis and Osteoarthritis
Authors: De Kleijn P. , Van Genderen F. R. , Van Meeteren N. L. U.
Published: July 2005

Summary.  People with haemophilia experience a progressive deterioration of their functional health status. Regular clinical assessment of functional health status provides insight into their process of disablement. As such, the development of a core‐set of measurement tools is warranted. The aim of this study was to gather data to prepare a (preliminary) core set of clinically relevant and feasible instruments to assess the functional health status of adults with haemophilia, and to indicate their psychometric qualities. Therefore, clinimetric instruments frequently used in two haemophilia‐resembling diseases (Rheumatoid Arthritis and Osteoarthritis) were reviewed from the literature. An extensive search in Medline yielded 13 relevant review articles, incorporating a total of 182 instruments, of which 40 were appropriate for haemophilia. Of these 40 instruments 3 measure body structures, 13 body functions, 19 activities (of which 5 are performance based and 14 self‐report based), and 3 measure participation. This classification is based on the International Classification of Functioning, Disability and Health. Detailed information regarding the psychometrics (reliability, validity and responsiveness) of four instruments is described fully in the literature, whereas the psychometrics of the majority of the other instruments are only partly described. The results of this literature study may contribute to the formation of a (preliminary) core set of clinimetric instruments to assess the functional health status of adults with haemophilia. Decisions on the final core set should be held within the Musculoskeletal Committee of the World Federation of Haemophilia.
Third ventricular chordoid glioma: clinicopathological study of two cases with evidence for a poor clinical outcome despite low grade histological features
Authors: Kurian K. M. , Summers D. M. , Statham P. F. X. , Smith C. , Bell J. E. , Ironside J. W.
Published: July 2005

Chordoid glioma of the third ventricle is a rare glial tumour whose precise histogenesis remains uncertain. We describe two cases that presented recently to our department and review the background literature. The neoplasm tends to occur in women and its clinical presentation is variable, resulting from acute hydrocephalus or impingement upon local structures. However, the radiological appearance is distinct, with an ovoid shape, hyperdensity and uniform contrast enhancement on computerized tomography and magnetic resonance imaging. Intraoperative smear diagnosis is difficult because of the lack of specific features, although the presence of metachromatic extracellular mucin may be useful. The characteristic histological appearance is that of cords and clusters of cohesive, oval‐to‐polygonal epithelioid cells with abundant eosinophilic cytoplasm and a mucinous background. There is often a mixed chronic inflammatory infiltrate with lymphocytes and plasma cells with Russell bodies. The main differentials for histological diagnosis include chordoid meningiomas, pilocytic astrocytomas and ependymomas. An immunohistochemical panel including antibodies to glial fibrillary acidic protein, CD34, epithelial membrane antigen, pan cytokeratin, S100 and vimentin can be used to distinguish between these possibilities. Ultrastructurally the tumour cells have basal lamina and microvilli, reminiscent of ependymomas. The clinical outcome in our cases was poor because of the location of the lesion and its close relation to the hypothalamus. Limited follow‐up after surgery with or without radiotherapy suggests that as‐full‐as‐possible resection favours a better outcome, although surgery in this area carries significant operative risks.
Repopulation of oligodendrocyte progenitor cell‐depleted tissue in a model of chronic demyelination
Authors: Foote A. K. , Blakemore W. F.
Published: July 2005

Some, but not all, chronically demyelinated multiple sclerosis (MS) lesions are depleted of oligodendrocyte progenitor cells (OPCs) suggesting that OPCs are destroyed during the process of demyelination and some factor impedes OPC repopulation of the depleted tissue. The chronically demyelinated axons in MS lie in an astrocytic environment and it has been proposed that this might impede entry of OPCs into such regions. By depleting a short length of spinal cord of its OPCs using 40 Gy of X‐irradiation in both normal rats and rats with progressive myelin loss accompanied by an astrocytosis (taiep rats), we investigated whether such changes affect the ability of OPCs to repopulate OPC‐depleted tissue. In both taiep and normal rats, the rate of repopulation decreases with age, but no difference was detected in the rate at which OPCs repopulated normally myelinated and chronically demyelinated and astrocytosed tissue. This indicates that, if the astrocytic environment of the taiep central nervous system (CNS) is comparable to that found in MS lesions, then the presence of chronically demyelinated axons and astrocytosis in chronic MS lesions does not represent a barrier to repopulation of the tissue by OPCs. However, similar to the situation in the normal adult rodent CNS, the rate of repopulation by endogenous OPCs in aged taiep rats is very slow, approximately 0.2 mm per week.
Depression in the elderly: pathological study of raphe and locus ceruleus
Authors: Syed A. , Chatfield M. , Matthews F. , Harrison P. , Brayne C. , Esiri M. M.
Published: July 2005

Depressive symptoms in the elderly are common and disabling and constitute a risk factor for the development of Alzheimer's disease (AD). One hypothesis worth exploring is that depression in the elderly is related to development of AD pathology at subcortical sites before such pathology develops in the hippocampus and neocortex. We describe here an autopsy study of the locus ceruleus (LC) and raphe nuclei (RN) in nine subjects with depression and 18 age and sex matched controls that were included in a community‐based study of cognitive function and ageing (MRC‐CFAS). We found no relationship between depression and (1) mean counts of serotonergic or total RN neuronal profiles (2) noradrenergic or total LC neuronal profiles (3) counts of neurofibrillary tangles in these nuclei, or (4) size of neurones in the RN. Nor were these parameters related to age or sex of the subjects. We conclude that depression in the elderly is unlikely to be related to RN or LC neurone counts or RN cell size or to AD‐type pathology in these nuclei. However, because of the small numbers of cases studied and our inability to carry out a full stereological study because of tissue limitations the findings are preliminary.
Relationship of neurofibrillary pathology to cerebral amyloid angiopathy in Alzheimer's disease
Authors: Williams S. , Chalmers K. , Wilcock G. K. , Love S.
Published: July 2005

Over 90% of patients with Alzheimer's disease (AD) develop cerebral amyloid angiopathy (CAA). Severe dyshoric CAA, in which amyloid extends into the surrounding brain parenchyma, may be associated with adjacent clustering of tau‐immunopositive neurites but the relationship of CAA to neurofibrillary pathology has not been systematically investigated. In the present study this relationship was examined in sections of frontal, temporal and parietal cortex from 25 AD patients with moderate to severe CAA and 26 with mild or absent CAA. We measured immunolabelling of abnormally phosphorylated tau adjacent to Aβ‐laden and non‐Aβ‐laden arteries and arterioles, and in cortex away from arteries and arterioles. We also analysed the possible influence of APOE genotype on these measurements. There were no significant differences between the lobes in measurements of tau labelling, either around blood vessels or elsewhere in the cortex. However, tau labelling around Aβ‐laden arteries and arterioles significantly exceeded that around non‐Aβ‐laden blood vessels (P < 0.001) and this, in turn was greater than the labelling of cortex away from blood vessels (P < 0.001). There was no association between APOE ɛ4 and the immunolabelling density for tau, whether around amyloid‐ or non‐amyloid‐laden arteries and arterioles, or in the cerebral cortex away from these. We propose that both CAA and peri‐vascular accumulation of hyperphosphorylated tau may be a consequence of elevated levels of soluble Aβ around cortical arteries and arterioles.
Survivin is a negative prognostic marker in medulloblastoma
Authors: Pizem J. , Cör A. , Zadravec‐Zaletel L. , Popovic M.
Published: July 2005

Survivin is a member of the inhibitor of apoptosis protein family, which is over‐expressed in many human cancers. Our aim was to analyse survivin expression in medulloblastoma, its association with aberrant activation of the WNT (wingless) pathway and to test the prognostic significance of survivin expression.

We immuno histochemically analysed survivin expression and localization of β‐catenin, a downstream mediator of the WNT pathway, in 56 cases of medulloblastoma.

Survivin was detected in the nuclei of tumour cells in all cases, but the proportion of positive nuclei varied from 0.5 to 31.3%. Survivin expression tended to be higher in medulloblastomas with an aberrant activation of the WNT pathway (nuclear localization of β‐catenin), but did not correlate with histological type, age group or dissemination via cerebrospinal fluid pathways. Survivin expression and dissemination status were two independent negative prognostic variables for the overall survival of patients with medulloblastoma.

In conclusion, survivin is up‐regulated in medulloblastomas. It is a negative prognostic marker and a potential therapeutic target.
NeuN expression correlates with reduced mitotic index of neoplastic cells in central neurocytomas
Authors: Englund C. , Alvord E. C. , Folkerth R. D. , Silbergeld D. , Born D. E. , Small R. , Hevner R. F.
Published: July 2005

In the developing brain, neuronal differentiation is associated with permanent exit from the mitotic cycle. This raises the possibility that neuronal differentiation may suppress proliferative activity, even in neoplastic cells. As a first step towards understanding the relation between neuronal differentiation and mitotic cycling in brain tumours, we studied the expression of NeuN (a neuronal marker) and Ki‐67 (a mitotic marker) by double‐labelling immuno‐fluorescence in 16 brain tumours with neuronal differentiation. The tumours included a series of 11 central neurocytomas, and five single cases of other tumour types. In the central neurocytomas, NeuN+ cells had a 15‐fold lower Ki‐67 labelling index, on average, than did NeuN– cells (P < 0.01). In the other tumours (one extraventricular neurocytoma, one desmoplastic medulloblastoma, one olfactory neuroblastoma, one ganglioglioma and one anaplastic ganglioglioma), the Ki‐67 labelling index was always at least fourfold lower in NeuN+ cells than in NeuN– cells. These results indicate that neuronal differentiation is associated with a substantial decrease of proliferative activity in neoplastic cells of central neurocytomas, and suggest that the same may be true across diverse types of brain tumours. However, tumours with extensive neuronal differentiation may nevertheless have a high overall Ki‐67 labelling index, if the mitotic activity of NeuN– cells is high. The correlation between NeuN expression and reduced mitotic activity in neurocytoma cells is consistent with the hypothesis that neuronal differentiation suppresses proliferation, but further studies will be necessary to determine causality and investigate underlying mechanisms.
Return of the cycad hypothesis – does the amyotrophic lateral sclerosis/parkinsonism dementia complex (ALS/PDC) of Guam have new implications for global health?
Authors: Ince P. G. , Codd G. A.
Published: July 2005

Recently published work provides evidence in support of the cycad hypothesis for Lytico–Bodig, the Guamanian amyotrophic lateral sclerosis/parkinsonism dementia complex (ALS/PDC), based on a new understanding of Chamorro food practices, a cyanobacterial origin of β‐methylaminoalanine (BMAA) in cycad tissue, and a possible mechanism of biomagnification of this neurotoxic amino acid in the food chain. BMAA is one of two cycad chemicals with known neurotoxic properties (the other is cycasin, a proven developmental neurotoxin) among the many substances that exist in these highly poisonous plants, the seeds of which are used by Chamorros for food and medicine. The traditional diet includes the fruit bat, a species that feeds on cycad seed components and reportedly bioaccumulates BMAA. Plant and animal proteins provide a previously unrecognized reservoir for the slow release of this toxin. BMAA is reported in the brain tissue of Guam patients and early data suggest that some Northern American patients dying of Alzheimer's disease (AD) have detectable brain levels of BMAA. The possible role of cyanobacterial toxicity in sporadic neurodegenerative disease is therefore worthy of consideration. Recent neuropathology studies of ALS/PDC confirm understanding of this disorder as a ‘tangle’ disease, based on variable anatomical burden, and showing biochemical characteristics of ‘AD‐like’ combined 3R and 4R tau species. This model mirrors the emerging view that other neurodegenerative disease spectra comprise clusters of related syndromes, owing to common molecular pathology, with variable anatomical distribution in the nervous system giving rise to different clinical phenotypes. Evidence for ‘ubiquitin‐only’ inclusions in ALS/PDC is weak. Similarly, although there is evidence for α‐synucleinopathy in ALS/PDC, the parkinsonian component of the disease is not caused by Lewy body disease. The spectrum of sporadic AD includes involvement of the substantia nigra and a high prevalence of ‘incidental’α‐synucleinopathy in sporadic AD is reported. Therefore the pathogenesis of Lytico–Bodig appears still to have most pertinence to the ongoing investigation of the pathogenesis of AD and other tauopathies.
Signalling and cell death in ozone‐exposed plants
Authors: KANGASJÄRVI JAAKKO , JASPERS PINJA , KOLLIST HANNES
Published: July 2005

Experiments with Arabidopsis mutants and sensitive and tolerant pairs in several other species have elucidated the molecular basis of plant ozone sensitivity and ozone lesion development. They have indicated an important role for hormonal signalling in determining the outcome of ozone challenge at the cellular level. The reactive oxygen species (ROS) from ozone degradation can cause either direct necrotic damage or induce the process of programmed cell death. Perception of ozone or ROS from its degradation in the apoplast activates several signal transduction pathways that regulate the responses of the cells to the increased oxidative load. Plant hormones salicylic acid, jasmonic acid, ethylene and abscisic acid are involved in determining the duration and extent of ozone‐induced cell death and its propagation. Salicylic acid is required for the programmed cell death, ethylene promotes endogenous ROS formation and lesion propagation, and jasmonic acid is involved in limiting the lesion spreading. Abscisic acid is most likely involved through the regulation of stomata and thus is expected to affect lesion initiation. The roles and interactions of perception of ozone, the immediate downstream responses, hormone biosynthesis and signalling during ozone lesion initiation and formation are reviewed.