Showing papers by "University of Antwerp published in 2004"

Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A.

Abstract: We report missense mutations in the mitochondrial fusion protein mitofusin 2 (MFN2) in seven large pedigrees affected with Charcot-Marie-Tooth neuropathy type 2A (CMT2A). Although a mutation in kinesin family member 1B-β (KIF1B) was associated with CMT2A in a single Japanese family, we found no mutations in KIF1B in these seven families. Because these families include all published pedigrees with CMT2A and are ethnically diverse, we conclude that the primary gene mutated in CMT2A is MFN2.

Formation of Secondary Organic Aerosols Through Photooxidation of Isoprene

Abstract: Detailed organic analysis of natural aerosols from the Amazonian rain forest showed considerable quantities of previously unobserved polar organic compounds, which were identified as a mixture of two diastereoisomeric 2-methyltetrols: 2-methylthreitol and 2-methylerythritol. These polyols, which have the isoprene skeleton, can be explained by OH radical-initiated photooxidation of isoprene. They have low vapor pressure, allowing them to condense onto preexisting particles. It is estimated that photooxidation of isoprene results in an annual global production of about 2 teragrams of the polyols, a substantial fraction of the Intergovernmental Panel on Climate Change estimate of between 8 and 40 teragrams per year of secondary organic aerosol from biogenic sources.

The Collaborative Cross, a community resource for the genetic analysis of complex traits

Abstract: The goal of the Complex Trait Consortium is to promote the development of resources that can be used to understand, treat and ultimately prevent pervasive human diseases. Existing and proposed mouse resources that are optimized to study the actions of isolated genetic loci on a fixed background are less effective for studying intact polygenic networks and interactions among genes, environments, pathogens and other factors. The Collaborative Cross will provide a common reference panel specifically designed for the integrative analysis of complex systems and will change the way we approach human health and disease.

Mass spectrometry in the structural analysis of flavonoids

Abstract: Flavonoids are very common and widespread secondary plant metabolites. They have a wide range of biological and physiological activities and serve as chemotaxonomic marker compounds. Therefore, they have been extensively investigated both in the past and during recent years. The interest in them is still increasing. In the search for new compounds, and also in quality control, there is a need to have reliable methodology for the analysis of flavonoids. Mass spectrometry can make an invaluable contribution because of its high sensitivity, possibilities of coupling with liquid chromatography and the availability of powerful tandem mass spectrometric techniques. A review of currently available mass spectrometric methodology used in the structure elucidation of flavonoids is presented. Sample preparation, liquid chromatographic/mass spectrometric analysis and tandem mass spectrometric procedures for the characterization of flavonoid aglycones, O-glycosides, C-glycosides and acylated glycosides are considered.

DNA/RNA Helicase Gene Mutations in a Form of Juvenile Amyotrophic Lateral Sclerosis (ALS4)

Abstract: Juvenile amyotrophic lateral sclerosis (ALS4) is a rare autosomal dominant form of juvenile amyotrophic lateral sclerosis (ALS) characterized by distal muscle weakness and atrophy, normal sensation, and pyramidal signs. Individuals affected with ALS4 usually have an onset of symptoms at age Senataxin gene ( SETX ). The SETX gene encodes a novel 302.8-kD protein. Although its function remains unknown, SETX contains a DNA/RNA helicase domain with strong homology to human RENT1 and IGHMBP2, two genes encoding proteins known to have roles in RNA processing. These observations of ALS4 suggest that mutations in SETX may cause neuronal degeneration through dysfunction of the helicase activity or other steps in RNA processing.

Mutant small heat-shock protein 27 causes axonal Charcot-Marie-Tooth disease and distal hereditary motor neuropathy

Abstract: Charcot-Marie-Tooth disease (CMT) is the most common inherited neuromuscular disease and is characterized by considerable clinical and genetic heterogeneity. We previously reported a Russian family with autosomal dominant axonal CMT and assigned the locus underlying the disease (CMT2F; OMIM 606595) to chromosome 7q11-q21 (ref. 2). Here we report a missense mutation in the gene encoding 27-kDa small heat-shock protein B1 (HSPB1, also called HSP27) that segregates in the family with CMT2F. Screening for mutations in HSPB1 in 301 individuals with CMT and 115 individuals with distal hereditary motor neuropathies (distal HMNs) confirmed the previously observed mutation and identified four additional missense mutations. We observed the additional HSPB1 mutations in four families with distal HMN and in one individual with CMT neuropathy. Four mutations are located in the Hsp20-alpha-crystallin domain, and one mutation is in the C-terminal part of the HSP27 protein. Neuronal cells transfected with mutated HSPB1 were less viable than cells expressing the wild-type protein. Cotransfection of neurofilament light chain (NEFL) and mutant HSPB1 resulted in altered neurofilament assembly in cells devoid of cytoplasmic intermediate filaments.

Antibiotic Therapy for Klebsiella pneumoniae Bacteremia: Implications of Production of Extended-Spectrum β-Lactamases

Abstract: The prevalence of extended-spectrum b-lactamase (ESBL) production by Klebsiella pneumonia approaches 50% in some countries, with particularly high rates in eastern Europe and Latin America. No randomized trials have ever been performed on treatment of bacteremia due to ESBL-producing organisms; existing data comes only from retrospective, single-institution studies. In a prospective study of 455 consecutive episodes of Klebsiella pneumoniae bacteremia in 12 hospitals in 7 countries, 85 episodes were due to an ESBL–producing organism. Failure to use an antibiotic active against ESBL-producing K. pneumoniae was associated with extremely high mortality. Use of a carbapenem (primarily imipenem) was associated with a significantly lower 14-day mortality than was use of other antibiotics active in vitro. Multivariate analysis including other predictors of mortality showed that use of a carbapenem during the 5-day period after onset of bacteremia due to an ESBL-producing organism was independently associated with lower mortality. Antibiotic choice is particularly important in seriously ill patients with infections due to ESBL-producing K. pneumoniae.

Solid-phase microextraction: a powerful sample preparation tool prior to mass spectrometric analysis.

Abstract: Sample preparation is an essential step in analysis, greatly influencing the reliability and accuracy of resulted the time and cost of analysis. Solid-Phase Microextraction (SPME) is a very simple and efficient, solventless sample preparation method, invented by Pawliszyn in 1989. SPME has been widely used in different fields of analytical chemistry since its first applications to environmental and food analysis and is ideally suited for coupling with mass spectrometry (MS). All steps of the conventional liquid-liquid extraction (LLE) such as extraction, concentration, (derivatization) and transfer to the chromatograph are integrated into one step and one device, considerably simplifying the sample preparation procedure. It uses a fused-silica fibre that is coated on the outside with an appropriate stationary phase. The analytes in the sample are directly extracted to the fibre coating. The SPME technique can be routinely used in combination with gas chromatography, high-performance liquid chromatography and capillary electrophoresis and places no restriction on MS. SPME reduces the time necessary for sample preparation, decreases purchase and disposal costs of solvents and can improve detection limits. The SPME technique is ideally suited for MS applications, combining a simple and efficient sample preparation with versatile and sensitive detection. This review summarizes analytical characteristics and variants of the SPME technique and its applications in combination with MS.

Development of a Multiplex PCR for the Detection of asa1, gelE, cylA, esp, and hyl Genes in Enterococci and Survey for Virulence Determinants among European Hospital Isolates of Enterococcus faecium

Abstract: A multiplex PCR for the simultaneous detection of five virulence genes (asa1, gelE, cylA, esp, and hyl) in enterococci was developed. The presence of these genes was investigated in 153 clinical and 118 fecal Enterococcus faecium isolates from inpatients at an increased risk of developing infections (such as patients in intensive care units and hematology wards) from 13 hospitals in eight European countries. Of the 271 E. faecium isolates, 135 were vancomycin resistant E. faecium (VREF) isolates and 136 were vancomycin susceptible E. faecium (VSEF) isolates. Susceptibilities to ampicillin, gentamicin, streptomycin, vancomycin, teicoplanin, ramoplanin, quinupristin-dalfopristin, and linezolid were tested by the microdilution method. Overall, the prevalence of esp was significantly higher (P = 0.03) in clinical VREF isolates (92%) than in fecal VREF isolates (73%). In Italy, the prevalence of esp was significantly higher (P = 0.02) in VREF isolates (91%) than in VSEF isolates (68%), whereas in the United Kingdom, hyl was significantly more prevalent (P = 0.01) in VREF isolates (71%) than in VSEF isolates (29%). No significant differences were found for the other countries. Pulsed-field gel electrophoresis was used to check the clonality among the strains tested and showed the spread of two center-specific (esp-positive) VREF clones in Italy and one center-specific (hyl-positive) clone in the United Kingdom. These clones were resistant to ampicillin, gentamicin, and streptomycin. The multiplex PCR reported in this study is a convenient and rapid method for the simultaneous detection of the virulence genes asa1, gelE, cylA, esp, and hyl in enterococci. Molecular analysis showed the intrahospital spread of esp-positive VREF clones (in Italy) and hyl-positive VREF clones (in the United Kingdom); the role of hyl remains to be elucidated.

Efficient isolation and solubilization of pristine single-walled nanotubes in bile salt micelles

Abstract: We have investigated a wide variety of surfactants for their efficiency in dissolving isolated single-walled carbon nanotubes (SWNTs) in water. In doing so, we have completely avoided the harsh chemical or mechanical conditions, such as acid or ultrasonic treatments, that are known to damage SWNTs. Bile salts in particular are found to be exceptionally effective in dissolving individual tubes, as evidenced by highly resolved optical absorption spectra, bright bandgap fluorescence, and the unprecedented resolution (∼ 2.5 cm - 1 ) of the radial breathing modes in Raman spectra. This is attributed to the formation of very regular and stable micelles around the nanotubes providing an unusually homogeneous environment. Quantitative information concerning the degree of solubilization is obtained from absorption spectroscopy.

Hot-spot residue in small heat-shock protein 22 causes distal motor neuropathy.

Abstract: Distal hereditary motor neuropathies are pure motor disorders of the peripheral nervous system resulting in severe atrophy and wasting of distal limb muscles. In two pedigrees with distal hereditary motor neuropathy type II linked to chromosome 12q24.3, we identified the same mutation (K141N) in small heat-shock 22-kDa protein 8 (encoded by HSPB8; also called HSP22). We found a second mutation (K141E) in two smaller families. Both mutations target the same amino acid, which is essential to the structural and functional integrity of the small heat-shock protein alphaA-crystallin. This positively charged residue, when mutated in other small heat-shock proteins, results in various human disorders. Coimmunoprecipitation experiments showed greater binding of both HSPB8 mutants to the interacting partner HSPB1. Expression of mutant HSPB8 in cultured cells promoted formation of intracellular aggregates. Our findings provide further evidence that mutations in heat-shock proteins have an important role in neurodegenerative disorders.

Proanthocyanidins in Health Care: Current and New Trends

Abstract: Polyphenolic compounds are widely distributed in higher plants and are an integral part of the human diet. Recent interest in these substances has been stimulated by their potential health benefits, which are believed to arise mainly from their antioxidant activity. In the past years, the antioxidant activity of flavonoids has been studied in detail. An important but often overlooked group of polyphenols is that of the proanthocyanidins. Therefore, the present review is focused mainly on the antioxidant activity of proanthocyanidins and its relevancy in vivo. The three most important mechanisms of their antioxidant action will be discussed, i.e. free radical scavenging activity, chelation of transition metals, and inhibition of enzymes. In addition, the protective role of proanthocyanidins against lipid peroxidation and peroxynitrite, as well as their antimicrobial properties will be discussed. To study the in vivo relevancy of the proanthocyanidin activities, the knowledge of their pharmacokinetic parameters is crucial. Although bioavailability and metabolism data on polyphenols in general and proanthocyanidins in particular are still largely unavailable, the first reports indicate that at least monomers and smaller oligomeric procyanidins are absorbed. There is also considerable scientific and public interest in the important role that antioxidants may play in health care, e.g. by acting as cancer chemopreventive and anti-inflammatory agents and by reducing risk of cardiovascular mortality. Each of these aspects will be discussed, with special attention to the role of proanthocyanidins on apoptosis, gene expression and transcription factors, such as NF-kappa B.

Rwanda, ten years on: From genocide to dictatorship

Abstract: In the spring of 1994, a small and poor country hitherto unknown to the public at large suddenly became international front-page news. Following the shooting down of President Habyarimana’s aircraft, a low-intensity civil war that had started in 1990 and been supposedly ended by the Arusha Accord (August 1993) resumed; a genocide and large-scale massacres claimed the lives of over a million Rwandans between 7 April and the beginning of July 1994. Although the violence could be seen almost live on television, the international community did nothing to stop the carnage. The United Nations peace-keeping mission United Nations Assistance Mission for Rwanda (UNAMIR) was all but withdrawn and it took weeks to formally recognize the violence for what it was — genocide.

Loss-of-function mutations in LEMD3 result in osteopoikilosis, Buschke-Ollendorff syndrome and melorheostosis.

Abstract: Osteopoikilosis, Buschke-Ollendorff syndrome (BOS) and melorheostosis are disorders characterized by increased bone density. The occurrence of one or more of these phenotypes in the same individual or family suggests that these entities might be allelic. We collected data from three families in which affected individuals had osteopoikilosis with or without manifestations of BOS or melorheostosis. A genome-wide linkage analysis in these families, followed by the identification of a microdeletion in an unrelated individual with these diseases, allowed us to map the gene that is mutated in osteopoikilosis. All the affected individuals that we investigated were heterozygous with respect to a loss-of-function mutation in LEMD3 (also called MAN1), which encodes an inner nuclear membrane protein. A somatic mutation in the second allele of LEMD3 could not be identified in fibroblasts from affected skin of an individual with BOS and an individual with melorheostosis. XMAN1, the Xenopus laevis ortholog, antagonizes BMP signaling during embryogenesis. In this study, LEMD3 interacted with BMP and activin-TGFbeta receptor-activated Smads and antagonized both signaling pathways in human cells.

Molecular and morphological data reveal cryptic taxonomic diversity in the terrestrial slug complex Arion subfuscus/fuscus (Mollusca, Pulmonata, Arionidae) in continental north‐west Europe

Abstract: The importance and abundance of cryptic species among invertebrate taxa is well documented. Nowadays, taxonomic, phylogenetic and conservation biological studies frequently use molecular markers to delineate cryptic taxa. Such studies, however, often face the problem of the differential resolution of the molecular markers and techniques involved. This issue is explored in the present study of cryptic taxa within the terrestrial slug complex Arion subfuscus/fuscus in continental north-west Europe. To this end, morphological, allozyme and mitochondrial 16S rDNA sequence data have been jointly evaluated. Using allozyme data and gonad type, two distinct groups were consistently delineated, even under sympatric conditions. The 16S rDNA data strongly supported both those groups and even suggested the presence of three distinct taxa within one of them. However, in view of: (1) the allopatric distribution of three OTUs, (2) the lack of allozyme or morphological differentiation, and (3) the extremely high degree of intraspecific mtDNA variation reported in pulmonate gastropods, they are, for the time being, not regarded as valid species under the biological species concept. By means of 16S rDNA and allozyme data, the position of type and topotype material of A. subfuscus s.s. and A. fuscus relative to the newly defined OTUs was determined, thus clarifying the nomenclature of this species complex. Additionally, gonad type proved to be a useful character for distinguishing the two species in north-west Europe.

Structures, Processes and Relational Mechanisms for IT Governance

Abstract: In many organisations, Information Technology (IT) has become crucial in the support, the sustainability and the growth of the business. This pervasive use of technology has created a critical dependency on IT that calls for a specific focus on IT Governance. IT Governance consists of the leadership and organisational structures and processes that ensure that the organisation’s IT sustains and extends the organisation’s strategy and objectives. This introductory chapter records and interprets some important existing theories, models and practises in the IT Governance domain and aims to contribute to the understanding of IT Governance and its structures, processes and relational mechanisms. This chapter appears in the book, Strategies for Information Technology Governance, edited by Wim Van Grembergen. Copyright © 2004, Idea Group Inc. Copying or distributing in print or electronic forms without written permission of Idea Group Inc. is prohibited. 701 E. Chocolate Avenue, Suite 200, Hershey PA 17033-1240, USA Tel: 717/533-8845; Fax 717/533-8661; URL-http://www.idea-group.com IDEA GROUP PUBLISHING 2 Van Grembergen, De Haes & Guldentops Copyright © 2004, Idea Group Inc. Copying or distributing in print or electronic forms without written permission of Idea Group Inc. is prohibited. INTRODUCTION Information Technology (IT) has become pervasive in current dynamic and often turbulent business environments. While in the past, business executives could delegate, ignore or avoid IT decisions, this is now impossible in most sectors and industries (Peterson, 2003; Duffy, 2002; Van Der Zee & De Jong, 1999). To emphasise this pervasiveness, Broadbent and Weill (1998) refer to three layers of the ‘new infrastructure’: local IT for business processes, firm IT infrastructure and public IT infrastructures (Figure 1). The Public Infrastructure (Figure 1) is the foundation of the New Infrastructure, which is in turn linked to external industry infrastructures such as Internet, EDI networks, etc. This enables the business to communicate and do business with customers, suppliers, partners, etc. Together with the Firm Information Technology Infrastructure, such as e-mail, customer databases, etc., these infrastructures make up the New Infrastructure. The New Infrastructure, plus the local IT needed to perform business processes, can be defined as the Firm Information Technology Portfolio. The Information Technology Portfolio not only has the potential to support existing business strategies, but also to shape new strategies (Henderson, Venkatraman, & Oldach, 1993; Henderson & Venkatraman, 1993; Guldentops, 2003). In this mindset, IT becomes not only a success factor for survival and prosperity, but also an opportunity to differentiate and to achieve competitive advantage. IT also offers a means for increasing productivity. Leveraging IT successfully to transform the enterprise and create products and services with added value has become a universal business competency (Guldentops, 2003). In this viewpoint, the IT department moves from a commodity service provider to a strategic partner, as illustrated by Venkatraman (1999) (Table 1). Broadbent, M. & Weill, P. (1998). Leveraging the New Infrastructure – How Market Leaders Capitalize on Information Technology. Harvard Business School Press. Figure 1. The New Infrastructure Public infrastructure (e.g. internet, vendors, industry networks) Firm Information Technology Infrastructure (e.g. home page, customer database, e-mail) Local IT for Business Processes Local IT for Business Processes Local IT for Business Processes 34 more pages are available in the full version of this document, which may be purchased using the "Add to Cart" button on the publisher's webpage: www.igi-global.com/chapter/structures-processes-relationalmechanisms-governance/29897

Container Shipping And Ports: An Overview

Abstract: Globalisation, deregulation, logistics integration and containerisation have reshaped the port and shipping industry. Port and maritime companies are challenged to redefine their functional role in the value chain for the sake of creating customer value and of ensuring the survival and growth of the company. Companies are busily trying to disrupt the status quo rather than preserve it. Based on empirical evidence, this paper demonstrates that because of the rapidly changing environment the port and liner shipping markets are not stable any longer. Individual terminal operators and shipping lines tend to walk different paths on a quest for higher margins and increased customer satisfaction. And more than once they (have to) change paths.

Heterozygous missense mutations in BSCL2 are associated with distal hereditary motor neuropathy and Silver syndrome

Abstract: Distal hereditary motor neuropathy (dHMN) or distal spinal muscular atrophy (OMIM #182960) is a heterogeneous group of disorders characterized by an almost exclusive degeneration of motor nerve fibers, predominantly in the distal part of the limbs(1). Silver syndrome (OMIM #270685) is a rare form of hereditary spastic paraparesis mapped to chromosome 11q12q14 (SPG17) in which spasticity of the legs is accompanied by amyotrophy of the hands and occasionally also the lower limbs(2,3). Silver syndrome and most forms of dHMN are autosomal dominantly inherited with incomplete penetrance and a broad variability in clinical expression. A genome-wide scan in an Austrian family with dHMN-V (ref. 4) showed linkage to the locus SPG17, which was confirmed in 16 additional families with a phenotype characteristic of dHMN or Silver syndrome. After refining the critical region to 1 Mb, we sequenced the gene Berardinelli-Seip congenital lipodystrophy (BSCL2) and identified two heterozygous missense mutations resulting in the amino acid substitutions N88S and S90L. Null mutations in BSCL2, which encodes the protein seipin, were previously shown to be associated with autosomal recessive Berardinelli-Seip congenital lipodystrophy 5 (OMIM #269700). We show that seipin is an integral membrane protein of the endoplasmic reticulum (ER). The amino acid substitutions N88S and S90L affect glycosylation of seipin and result in aggregate formation leading to neurodegeneration.

Knowledge, Attitudes and Practices in Travel-related Infectious Diseases: The European Airport Survey

Abstract: Background. The European Travel Health Advisory Board conducted a cross-sectional pilot survey to evaluate current travel health knowledge, attitudes and practices (KAP) and to determine where travelers going to developing countries obtain travel health information, what information they receive, and what preventive travel health measures they employ. Subsequently, the questionnaire used was improved and a cross-sectional, multicenter study was undertaken in airports in Europe, Asia, South Africa and the United States. This paper describes the methods used everywhere, and results from the European airports. Method. Between September 2002 and September 2003, 5,465 passengers residing in Europe and boarding an intercontinental flight to a developing country were surveyed at the departure gates of nine major airports in Europe. Questionnaires were self-administered, and checked for completeness and validated by trained interviewers. Results: Although the majority of travelers (73.3%) had sought general information about their destination prior to departure, only just over half of the responders (52.1%) had sought travel health advice. Tourists and people traveling for religious reasons had sought travel health advice more often, whereas travelers visiting friends and relatives were less likely to do so. Hepatitis A was perceived as the most probable among the infectious diseases investigated, followed by HIV and hepatitis B. In spite of a generally positive attitude towards vaccines, 58.4% and 68.7% of travelers could not report any protection against hepatitis A or hepatitis B, respectively. Only one in three travelers to a destination country with at least some malaria endemicity were carrying antimalarial drugs. Almost one in four travelers visiting a high-risk area had an inaccurate risk perception and even one in two going to a no-risk destination were unnecessarily concerned about malaria. Conclusions: The large variation in destinations, age of the travelers and reasons for traveling illustrates that traveling to a developing country has become common practice. The results of this large-scale airport survey clearly demonstrate an important educational need among those traveling to risk destinations. Initiatives to improve such education should target all groups of travelers, including business travelers, those visiting friends and relatives, and the elderly. Additionally, travel health advice providers should continue their efforts to make travelers comply with the recommended travel health advice. Our common objective is to help travelers stay healthy while abroad, and consequently to also reduce the potential importation of infectious diseases and the consequent public health and other implications.

The role of tau (MAPT) in frontotemporal dementia and related tauopathies.

Abstract: Tau is a multifunctional protein that was originally identified as a microtubule-associated protein. In patients diagnosed with frontotemporal dementia and parkinsonism linked to chromosome 17, mutations in the gene encoding tau (MAPT) have been identified that disrupt the normal binding of tau to tubulin resulting in pathological deposits of hyperphosphorylated tau. Abnormal filamentous tau deposits have been reported as a pathological characteristic in several other neurodegenerative diseases, including frontotemporal dementia, Pick Disease, Alzheimer disease, argyrophilic grain disease, progressive supranuclear palsy, and corticobasal degeneration. In the last five years, extensive research has identified 34 different pathogenic MAPT mutations in 101 families worldwide. In vitro, cell-free and transfected cell studies have provided valuable information on tau dysfunction and transgenic mice carrying human MAPT mutations are being generated to study the influence of MAPT mutations in vivo. This mutation update describes the considerable differences in clinical and pathological presentation of patients with MAPT mutations and summarizes the effect of the different mutations on tau functioning. In addition, the role of tau as a genetic susceptibility factor is discussed, together with the genetic evidence for additional causal genes for tau-positive as well as tau-negative dementia.

Increased Serum Interleukin-8 in Patients with Early and Metastatic Breast Cancer Correlates with Early Dissemination and Survival

Abstract: Purpose: The prognostic significance of serum interleukin (IL)-8 was evaluated in patients with metastatic breast cancer. The predictive value of serum IL-8 for the presence of occult metastatic tumor cells in bone marrow aspirates was evaluated in patients with operable and metastatic breast cancer. Experimental Design: Serum IL-8 was measured in healthy controls, patients with operable breast cancer, and patients with untreated, progressive metastatic breast cancer. In 69 patients with either operable or advanced breast cancer, occult cytokeratin-positive cells were counted in bone marrow aspirates. Results: Serum IL-8 levels are increased in 67% (52 of 77) of patients with advanced breast cancer. Overall, these levels are significantly higher in patients with breast cancer compared with healthy volunteers (P < 0.001). The IL-8 levels increase significantly in patients with more advanced disease. An elevated serum IL-8 is related to an accelerated clinical course, a higher tumor load, and the presence of liver or lymph node involvement. A multivariate analysis indicates that serum IL-8 is an independent significant factor for postrelapse survival. There was a significant difference between serum IL-8 levels in patients with or without occult cytokeratin-positive bone marrow cells (P < 0.04). Serum IL-8 levels also showed an association with the number of these cells (P < 0.01). Conclusions: Serum IL-8 is increased in patients with breast cancer and has an independent prognostic significance for postrelapse survival. The observations on the relationship between occult cytokeratin-positive bone marrow cells corroborate the concept of IL-8 acting as a contributor to the process of tumor cell dissemination. Similarly, the relationship between serum IL-8 and nodal stage at presentation deserves further study. These results further expand the concept that inflammation and inflammatory cytokines are critical components of tumor progression.

Examination of G72 and D-amino-acid oxidase as genetic risk factors for schizophrenia and bipolar affective disorder.

Abstract: A recent study has suggested that the brain-expressed genes for G72 and D-amino-acid oxidase (DAAO) exert an influence on susceptibility to schizophrenia Our aim was to replicate this finding in German schizophrenic patients and to assess whether G72 and DAAO might also contribute to the development of bipolar affective disorder We genotyped seven single-nucleotide polymorphisms (SNPs) in the G72 gene and three in the DAAO gene in 599 patients (299 schizophrenic, 300 bipolar) and 300 controls At G72, individual SNPs and a four-marker haplotype were associated with schizophrenia The most significant SNP as well as the haplotype were also associated with bipolar affective disorder (BPAD) DAAO was associated with schizophrenia, but not with BPAD The association of variation at G72 with schizophrenia as well as BPAD provides molecular support for the hypothesis that these two major psychiatric disorders share some of their etiologic background