bluuebunny/crossref_metadata_2025 huggingface dataset:
Database Based Reasoning for Real Time Monitoring and Data Analysis in Intensive Care Units
Authors: Dafonte J. C. , Arcay B. , Taboada J. A.
Published: December 2004

The complexity of the monitored data available in modern intensive care units (ICUs) means that they are best processed, for presentation to medical staff, by expert system techniques. This article describes an expert system that has an appropriately designed inference engine, handling the temporal considerations inherent in monitoring and manages data acquisition via a Medical Information Bus. Also, we will describe how we extended our monitoring system in ICUs by writing an interface allowing communication in dynamic SQL with a relational database management system. The extended system facilitates both permanent filing of case data and the use of filed data by the rules of the expert system, and allows automatic intelligent screening of data prior to permanent filing so as to ensure data reliability.
Goal‐driven automation of a deep space communications station: a case study in knowledge engineering for plan generation and execution
Authors: Hill, Jr. Randall W. , Chien Steve A. , Fayyad Kristina V.
Published: December 2004

Abstract:
This paper describes the application of Artificial Intelligence techniques for plan generation, plan execution, and plan monitoring to automate a Deep Space Communication Station. This automation allows a communication station to respond to a set of tracking goals by appropriately reconfiguring the communications hardware and software to provide the requested communications services. In particular this paper describes: (1) the overall automation architecture, (2) the plan generation and execution monitoring AI technologies used and implemented software components, and (3) the knowledge engineering process and effort required for automation. This automation was demonstrated in February 1995, at the DSS13 Antenna Station in Goldstone, CA on a series of Voyager tracks and the technologies demonstrated are being transferred to the operational Deep Space Network stations.
Reproductive epigenetics
Authors: Kelly TLJ , Trasler JM
Published: December 2004

Epigenetics refers to covalent modifications of DNA and core histones that regulate gene activity without altering DNA sequence. To date, the best‐characterized DNA modification associated with the modulation of gene activity is methylation of cytosine residues within CpG dinucleotides. Human disorders associated with epigenetic abnormalities include rare imprinting diseases, molar pregnancies, and childhood cancers. Germ cell development and early embryo development are critical times when epigenetic patterns are initiated or maintained. This review focuses on the epigenetic modification DNA methylation and discusses recent progress that has been made in understanding when and how epigenetic patterns are differentially established in the male and female germlines, the mouse, and human disorders associated with abnormalities in epigenetic programming in germ cells and early embryos, as well as genetic and other modulators (e.g. nutrition and drugs) of reproductive epigenetic events.
Admission Preferences for Minority Students, Athletes, and Legacies at Elite Universities*
Authors: Espenshade Thomas J. , Chung Chang Y. , Walling Joan L.
Published: December 2004

Objective. This study examines how preferences for different types of applicants exercised by admission offices at elite universities influence the number and composition of admitted students.

Methods. Logistic regression analysis is used to link information on the admission decision for 124,374 applications to applicants' SAT scores, race, athletic ability, and legacy status, among other variables.

Results. Elite universities give added weight in admission decisions to applicants who have SAT scores above 1500, are African American, or are recruited athletes. A smaller, but still important, preference is shown to Hispanic students and to children of alumni. The athlete admission “advantage” has been growing, while the underrepresented minority advantage has declined.

Conclusions. Elite colleges and universities extend preferences to many types of students, yet affirmative action—the only preference given to underrepresented minority applicants—is the one surrounded by the most controversy.
ERCP‐directed brush cytology prepared by the Thinprep® method: test performance and morphology of 149 cases
Authors: Duggan M. A. , Brasher P. , Medlicott S. A.
Published: December 2004

Conventionally prepared endobiliary brushings are moderately (42%) sensitive and highly (98%) specific in detecting malignancy. The performance and morphological features of brushings prepared by Thinprep®, a liquid‐based method are mostly unknown. All brushings were retrieved from the laboratory files. Disease was classified as benign or malignant by linkage with the provincial cancer registry and sensitivity, specificity, positive (PPV) and negative predictive values (NPV) calculated. True positives and negatives were reviewed and predictive morphological features analysed by regression tree analysis. Out of 149 brushings, 55 (37%) were positive and 94 (63%) negative. Malignancy was identified in 86 (58%) and benign disease in 63 (42%) of the cases. The sensitivity was 51%, specificity 83%, PPV 80% and NPV 55%. Absolute discriminants of positive and negative brushings were not found, but nuclear cytoplasmic ratio was a useful feature. The performance of Thinprep®‐prepared brushings from this anatomical site was comparable with conventional preparations.
Cellular microparticles: new players in the field of vascular disease?
Authors: Diamant M. , Tushuizen M. E. , Sturk A. , Nieuwland R.
Published: December 2004

Microparticles are small membrane vesicles that are released from cells upon activation or during apoptosis. Cellular microparticles in body fluids constitute a heterogeneous population, differing in cellular origin, numbers, size, antigenic composition and functional properties. Microparticles support coagulation by exposure of negatively charged phospholipids and sometimes tissue factor, the initiator of coagulation in vivo. Microparticles may transfer bioactive molecules to other cells or microparticles, thereby stimulating cells to produce cytokines, cell‐adhesion molecules, growth factors and tissue factor, and modulate endothelial functions. Microparticles derived from various cells, most notably platelets but also leucocytes, lymphocytes, erythrocytes and endothelial cells, are present in the circulation of healthy subjects. Rare hereditary syndromes with disturbances in membrane vesiculation leading to a decreased numbers of microparticles clinically present with a bleeding tendency. In contrast, elevated numbers of microparticles are encountered in patients with a great variety of diseases with vascular involvement and hypercoagulability, including disseminated intravascular coagulation, acute coronary syndromes, peripheral arterial disease, diabetes mellitus and systemic inflammatory disease. Finally, microparticles are a major component of human atherosclerotic plaques.

 In view of their functional properties, cell‐derived microparticles may be an important intermediate in the cascade of cellular and plasmatic dysfunctions underlying the process of atherogenesis.
Role of apoptosis and CD95‐receptor/ligand system in aspirin‐ and Helicobacter pylori‐induced cell death
Authors: Domhan S. , Stremmel W. , Rudi J.
Published: December 2004

Background  Helicobacter pylori and aspirin both induce gastric epithelial apoptosis. However, the apoptosis‐inducing mechanism of aspirin is still unknown.

Material and methods  Apoptosis induction was measured in several gastric epithelial cell lines after incubation with either aspirin or H. pylori supernatant or with a combination of both. CD95 expression was assessed by FACS analysis and CD95L mRNA was measured by reverse transcription polymerase chain reaction.

Results  It could be demonstrated that aspirin‐ and H. pylori supernatant‐induced apoptosis involves increased CD95 expression in three different gastric epithelial cell lines. The combined exposure of H. pylori supernatant and aspirin had synergistic effects on both apoptotic cell death and CD95 expression. Blockade of CD95 signalling with an antagonistic antibody was partially prevented from H. pylori‐ but not from aspirin‐induced apoptosis. Furthermore, CD95L expression was detected after treatment with H. pylori only.

Conclusions  These data suggest that although aspirin‐mediated CD95 up‐regulation is not relevant for its direct apoptotic effect it may sensitize gastric epithelial cells for H. pylori‐induced apoptosis. Collectively our data demonstrate the relation of aspirin‐ and H. pylori‐induced apoptosis from a new perspective.
Seston capture byHydropsyche siltalaiand the accuracy of capture efficiency estimates
Authors: Brown Sarah A. , Ruxton Graeme D. , Pickup Roger W. , Humphries Stuart
Published: December 2004

1. Suspension feeding by caseless caddisfly larvae (Trichoptera) constitutes a major pathway for energy flow, and strongly influences productivity, in streams and rivers.

2. Consideration of the impact of these animals on lotic ecosystems has been strongly influenced by a single study investigating the efficiency of particle capture of nets built by one species of hydropsychid caddisfly.

3. Using water sampling techniques at appropriate spatial scales, and taking greater consideration of local hydrodynamics than previously, we examined the size‐frequency distribution of particles captured by the nets ofHydropsyche siltalai. Our results confirm that capture nets are selective in terms of particle size, and in addition suggest that this selectivity is for particles likely to provide the most energy.

4. By incorporating estimates of flow diversion around the nets of caseless caddisfly larvae, we show that capture efficiency (CE) is considerably higher than previously estimated, and conclude that more consideration of local hydrodynamics is needed to evaluate the efficiency of particle capture.

5. We use our results to postulate a mechanistic explanation for a recent example of interspecific facilitation, whereby a reduction of near‐bed velocities seen in single species monocultures leads to increased capture rates and local depletion of seston within the region of reduced velocity.
Applying the developmental perspective in the psychiatric assessment and diagnosis of persons with intellectual disability: part I – assessment
Authors: Dosen A.
Published: December 2004

Background  In generic psychiatry there has been increasing interest among scientists for the developmental perspective. However, professionals active in the mental health care of people with intellectual disability (ID) have not shown the same degree of interest. The author of this article, who has had a liberal amount of rewarding experiences with the developmental approach in the field of ID, considers the developmental perspective to be innovative and very useful in psychiatric assessment, diagnosis and treatment of this population. The aim of the article is to stimulate a wider application of the developmental perspective as well as to challenge a professional discussion on this issue.

Methods  Basic assumptions of the developmental perspective are discussed and assessment tools and methods are described.

Results  In a case vignette, the advantages of developmentally based assessment are emphasized. Emotional development and personality development are viewed as the developmental components that play an important role in adaptive and maladaptive behaviour as well as in the onset and presentation of psychopathology. It is clear that interpretative insight into the totality of the psychosocial aspects of these individuals cannot only be obtained by measuring the level of cognitive development. A wider frame of mind is needed for unambiguous psychiatric diagnostics. Therefore, a replacement of the three dimensional paradigm (bio–psycho–social) by a four dimensional one (bio–psycho–socio–developmental) for the assessment and diagnosis of persons with ID is proposed.
Applying the developmental perspective in the psychiatric assessment and diagnosis of persons with intellectual disability: part II – diagnosis
Authors: Dosen A.
Published: December 2004

Background  The descriptive phenomenological categorical psychiatric diagnostic systems that are currently being used in the field of intellectual disability do not adequately provide for the special needs of persons with intellectual disability. Many relevant diagnostic questions are left unanswered or are only partially accounted for. This is particularly true for persons with low developmental levels.

Method  A solution to these stumbling blocks is sought in enhancing the contemporary categorical diagnostic systems by also applying methods derived from the developmental perspective.

Result  By taking the levels of emotional and personality development, in addition to other developmental aspects into account, the clinical picture becomes more comprehensible and explainable.

Conclusion  The integrative diagnosis that results from this combined approach provides an insight into the processes that have led to the disorder and enriches one's understanding of the presentation form of the disorder. This diagnosis is process‐ rather than symptom‐oriented and is particularly useful with persons who have a low level of psychosocial development.
Effect of provisional restorations on the final bond strengths of porcelain laminate veneers
Authors: AYKENT F. , USUMEZ A. , OZTURK A. N. , YUCEL M. T.
Published: December 2004

summary  The purpose of this in vitro study was to evaluate the effect of the different provisional restorations cementation techniques on the final bond strengths of porcelain laminate veneers (PLVs). Thirty‐six extracted human central incisors were sectioned 2 mm below the cemento‐enamel junction, and crown parts were embedded into self‐cure acrylic resin. Standardized PLV preparations were carried out on labial surfaces of the teeth. Then the teeth were randomly divided into three groups of 12 each. In group 1, provisional restorations were cemented with eugenol‐free cement. In group 2, prepared teeth surfaces were first coated with a desensitizing agent then provisional restorations were cemented with resin cement. In group 3, provisional restorations were not fabricated to serve as control. After specimens were stored in distilled water for 2 weeks, provisional restorations were removed and final IPS Empress 2 ceramic veneers were bonded with a dual‐curing resin. Two microtensile samples from each tooth measuring 1·2 × 1·2 × 5 mm were prepared. These sections were subjected to microtensile testing and failure values were recorded. The data were analysed by one‐way anova and Tukey HSD tests. The PLVs, placed on the tooth surface that had received a dentine desensitizer and provisional restorations luted with resin cement (group 2), showed the lowest bond strength in all test groups. But no statistically significant differences were found between the bond strength of PLVs in control group (no provisional restorations) and group 1 (provisional restorations cemented with eugenol‐free cement before final cementations). Scanning electron microscopic (SEM) examination of this study also showed that the bonding to enamel surface was better in control group and group 1 than group 2.
The measurement of tooth whiteness by image analysis and spectrophotometry: a comparison
Authors: GUAN Y. H. , LATH D. L. , LILLEY T. H. , WILLMOT D. R. , MARLOW I. , BROOK A. H.
Published: December 2004

summary  Digital image capturing and analysis techniques have been used to measure the colour of teeth and to compare with spectrophotometric results and visual observations. A non‐linear image analysis approach was developed and, for the colour range of human teeth, allows device‐dependant digital camera colour data to be quantitatively transformed to Commission Internationale de l’Éclairage (CIE) colorimetric values. With reference to a CIE standard illuminant, two different lighting arrays have been used. For flat and non‐translucent white and yellow surfaces, spectrophotometric results showed that this transformation achieves required accuracy. It was found, in all of the present studies, which included measurements on the VITA Lumin® Vacuum shade guide and extracted teeth, that spectrophotometry invariably underestimated values of the CIE whiteness index. However, the results from these two types of measurement correlated well. There was also a reasonably good correlation between earlier data obtained by visual assessment and the present data by the two instrumental methods. For extracted teeth, both instrumental methods used in this work did not confirm a whitening effect for 2‐min brushing with toothpaste, but did show significant whitening results for bleaching with 15% hydrogen peroxide.
Effect of dentine conditioners on the bonding efficacy of one‐bottle adhesives
Authors: CHENG J.‐T. , ITOH K. , KUSUNOKI M. , HASEGAWA T. , WAKUMOTO S. , HISAMITSU H.
Published: December 2004

summary  The bonding efficacy of four one‐bottle adhesives (OptiBond Solo Plus, Gluma Comfort Bond, One Step and Prime & Bond NT) and a multi‐step adhesive (Clearfil Photo Bond) as a control was evaluated. The dentine cavity wall was conditioned with phosphoric acid or ethylenediaminetetraacetic acid (EDTA) and the marginal integrity was estimated by measuring the wall‐to‐wall contraction gap width between the composite and the dentine cavity surface. In the positive control group, the adhesive was applied following glyceryl methacrylate (GM) priming. The analyses were performed by Kruskal–Wallis and Mann–Whitney U‐tests. One‐bottle adhesives were clearly inferior to the multi‐step bonding system in marginal integrity when dentine was conditioned with EDTA. The present findings also suggested that the marginal sealing ability of ethanol‐based one‐bottle systems was better than acetone‐based one‐bottle systems when dentine surfaces were conditioned with EDTA. Nevertheless, further investigations are needed on the function of fillers in one‐bottle adhesives for the prevention of contraction gaps.
In vitro degradation of polyurethane orthodontic elastomeric modules
Authors: ELIADES T. , ELIADES G. , SILIKAS N. , WATTS D. C.
Published: December 2004

summary  The objectives of this study were to investigate the structural characteristics of orthodontic polyurethane elastomeric modules and their changes produced by mechanical and chemical ageing. Three products were tested (Generation II, Dentaurum, Alastic). For each product four groups of modules were studied under the following conditions: as‐received (A0); after 3 weeks stretching at 50% elongation in air (B0); after 3 weeks immersion in an ethanol/water solution (3:1 v/v) to induce accelerated ageing (A1); and after 3 weeks immersion in the ethanol/water solution at 50% elongation, as above (B1). The chains and the solution extracts were characterized by micro‐MIR FTIR spectroscopy. Specimens of group B0 exhibited changes in peak intensities relative to the control group (A0), attributed to molecular orientation of poly (methylene glycol) soft segments and chain extenders such as butanediol. Moreover, group B0 showed differences in the ω(CH2)b peak at 1364 cm−1, attributed to oxidative degradation of α‐methylene groups by formation of ester, carboxylic acid or aldehyde groups due to hydrogen abstraction. Comparison of A1 and B1 groups with the controls (A0, B0) showed no major differences between their respective spectra, apart from the loss of the 1639 cm−1 peak attributed to ethylene NN bis (stearamide) wax. However, comparison of the spectra of the extracts from the elongated modules with the extracts of the controls revealed differences in the concentration of alcohol and alkene groups. The structural changes identified were the same in all the products tested and may indicate degradation mechanisms that could potentially hold intraorally.
Signaling of phosphorus deficiency‐induced gene expression in white lupin requires sugar and phloem transport
Authors: Liu Junqi , Samac Deborah A. , Bucciarelli Bruna , Allan Deborah L. , Vance Carroll P.
Published: December 2004

Roots of phosphorus (P)‐deficient white lupin exhibit striking changes in morphology and gene expression. In this report we provide further insight into genetic elements affecting transcription of P‐deficiency‐induced genes. Moreover, we also show that sugars and photosynthates are integrally related to P‐deficiency‐induced gene expression. White lupin phosphate transporter (LaPT1) and secreted acid phosphatase (LaSAP1) promoter‐reporter genes when transformed into alfalfa, a heterologous legume, showed significant induction in roots specifically in response to P‐deficiency. In addition, both promoters were active in nitrogen‐fixing root nodules but not in ineffective nodules indicating a link between P‐deficiency and factors related to nitrogen fixation/metabolism. As sugars play a role in signal transduction during nitrogen assimilation and are required for effective nitrogen fixation, we tested the relationship of sugars to P‐deficiency‐induced gene expression. Exogenous sucrose, glucose, and fructose stimulated LaPT1 and LaSAP1 transcript accumulation in dark‐grown P‐sufficient white lupin seedlings. Furthermore, in intact P‐deficient white lupin plants, LaPT1 and LaSAP1 expression in cluster roots was strikingly reduced in dark‐adapted plants with expression rapidly restored upon reexposure to light. Likewise, interruption of phloem supply to P‐deficient roots resulted in a rapid decline in LaPT1 and LaSAP1 transcript accumulation. Similar results were also obtained with a third lupin P‐deficiency‐induced gene encoding a putative multidrug and toxin efflux protein (LaMATE). Taken together, our data show that the regulation of P‐deficiency‐induced genes is conserved across plant species and sugars/photosynthates are crucial for P‐deficiency signal transduction.
Tobacco Mg protoporphyrin IX methyltransferase is involved in inverse activation of Mg porphyrin and protoheme synthesis
Authors: Alawady Ali E. , Grimm Bernhard
Published: December 2004

Protoporphyrin, a metabolic intermediate of tetrapyrrole biosynthesis, is metabolized by Mg chelatase and ferrochelatase and is directed into the Mg‐branch for chlorophyll synthesis and in the Fe‐branch for protoheme synthesis respectively. Regulation of the enzyme activities at the beginning of this branchpoint ensures accurate partition of protoporphyrin, but is still not entirely understood. Transgenic tobacco plants were generated that express antisense or sense RNA for inhibited and excessive expression of Mg protoporphyrin methyltransferase (MgPMT) respectively. This enzyme accepts Mg protoporphyrin from Mg chelatase and catalyses the transfer of a methyl group to the carboxyl group of the C13‐propionate side chain. Low MgPMT activity is correlated with reduced Mg chelatase activity and a low synthesis rate of 5‐aminolevulinate, but with enhanced ferrochelatase activity. In contrast, high MgPMT activity leads to inverse activity profiles: high activities of Mg chelatase and for 5‐aminolevulinate synthesis, but reduced activity of ferrochelatase, indicating a direct influence of MgPMT in combination with Mg chelatase on the metabolic flux of ALA and the distribution of protoporphyrin into the branched pathway. The modified enzyme activities in tetrapyrrole biosynthesis in the transgenic plants can be explained with changes of certain corresponding mRNA contents: increased 5‐aminolevulinate synthesis and Mg chelatase activity correlate with enhanced transcript levels of the HemA, Gsa, and CHLH gene encoding glutamyl‐tRNA reductase, glutamate‐1‐semialdehyde aminotransferase and a Mg chelatase subunit respectively. It is proposed that reduced and increased MgPMT activity in chloroplasts is communicated to the cytoplasm for modulating transcriptional activities of regulatory enzymes of the pathway.
Molecular diagnosis of hereditary hemochromatosis: application of a newly‐developed reverse‐hybridization assay in the South African population
Authors: Kotze MJ , De Villiers JNP , Bouwens CSH , Warnich L , Zaahl MG , Van Der Merwe S , Oberkanins C
Published: December 2004

A recently developed strip‐assay for hemochromatosis provides a rapid method for simultaneous detection of multiple mutations, which among others includes the HFE gene mutations V53M, V59M, H63D, H63H, S65C, Q127H, E168Q, and C282Y, previously detected in the general South African population using gel‐based mutation‐screening methods. The objective of the study was to determine the frequency of the relatively rare mutations in samples selected for altered iron parameters or a family history of hereditary hemochromatosis (HH) as part of the validation process of the assay for routine diagnostic purposes. The study population consisted of 451 individuals previously screened for mutations C282Y and H63D by restriction enzyme analysis in order to confirm or possibly exclude a diagnosis of HH. These individuals were subjected to mutation screening using the commercially available hemochromatosis strip‐assay. Previous positive results for mutations C282Y and H63D in 233 individuals confirmed the accuracy of the reverse‐hybridization assay. Mutation S65C was detected in 13 Caucasians, including three compound heterozygotes. These constituted 2% (13/600) of the chromosomes without mutations C282Y or H63D. The African‐specific HFE mutation V53M was detected in one out of 11 (9%) African subjects screened. Mutation E168Q was detected in a single Caucasian individual together with mutation H63D. Our data demonstrate the value of the strip‐based technology in providing a rapid and reliable comprehensive test for simultaneous analysis of multiple mutations.
Cognitive, language, and adaptive behavior profiles in individuals with a diagnosis of Cohen syndrome
Authors: Karpf J , Turk J , Howlin P
Published: December 2004

Although the physical characteristics of Cohen syndrome have been studied in considerable detail, data on other aspects of development are relatively limited. We report findings on cognitive, linguistic, and adaptive profiles in a group of 45 individuals clinically diagnosed with Cohen syndrome when aged between 4 and 49 years. The profile of skills observed was consistent with other recent findings. Thus, independence levels generally were poor, but socialization skills as assessed by the Vineland were relatively less impaired. This particular area of strength probably underlies the ‘sociable’ temperament typically associated with Cohen syndrome. However, the range of cognitive ability was wider than reported in most previous research, raising the issue of whether mental retardation should be considered as a necessary component of the phenotype. The implications for genetic testing are discussed.
Studying the genetics of Hirschsprung's disease: unraveling an oligogenic disorder
Authors: Brooks AS , Oostra BA , Hofstra RMW
Published: December 2004

Hirschsprung's disease is characterized by the absence of ganglion cells in the myenteric and submucosal plexuses of the gastrointestinal tract. Genetic dissection was successful as nine genes and four loci for Hirschsprung's disease susceptibility were identified. Different approaches were used to find these loci such as classical linkage in large families, identity by descent mapping in an inbred kindred, candidate gene approaches based on naturally occurring mutant mice models, and finally the use of model‐free linkage and association analyzes. In this study, we review the identification of genes and loci involved in the non‐syndromic common form and syndromic Mendelian forms of Hirschsprung's disease. The majority of the identified genes are related to Mendelian syndromic forms of Hirschsprung's disease. The non‐Mendelian inheritance of sporadic non‐syndromic Hirschsprung's disease proved to be complex; involvement of multiple loci was demonstrated in a multiplicative model. We discuss the practical implications of the elucidation of genes associated with Hirschsprung's disease susceptibility for genetic counseling. Finally, we speculate on possible strategies to identify new genes for Hirschsprung's disease.
Psychological impact of genetic testing for hereditary non‐polyposis colorectal cancer
Authors: Meiser B , Collins V , Warren R , Gaff C , St John DJB , Young M‐A , Harrop K , Brown J , Halliday J
Published: December 2004

The psychological impact of predictive genetic testing for hereditary non‐polyposis colorectal cancer (HNPCC) was assessed in 114 individuals (32 carriers and 82 non‐carriers) attending familial cancer clinics, using mailed self‐administered questionnaires prior to, 2 weeks, 4 months and 12 months after carrier status disclosure. Compared to baseline, carriers showed a significant increase in mean scores for intrusive and avoidant thoughts about colorectal cancer 2 weeks (t = 2.49; p = 0.014) and a significant decrease in mean depression scores 2 weeks post‐notification of result (t = −3.98; p < 0.001) and 4 months post‐notification of result (t = −3.22; p = 0.002). For non‐carriers, significant decreases in mean scores for intrusive and avoidant thoughts about colorectal cancer were observed at all follow‐up assessment time points relative to baseline. Non‐carriers also showed significant decreases from baseline in mean depression scores 2 weeks, 4 months and 12 months post‐notification. Significant decreases from baseline for mean state anxiety scores were also observed for non‐carriers 2 weeks post‐notification (t = −3.99; p < 0.001). These data indicate that predictive genetic testing for HNPCC leads to psychological benefits amongst non‐carriers, and no adverse psychological outcomes were observed amongst carriers.
DHCR7 mutations and genotype–phenotype correlation in 37 Polish patients with Smith–Lemli–Opitz syndrome
Authors: Ciara E , Nowaczyk MJM , Witsch‐Baumgartner M , Malunowicz E , Popowska E , Jezela‐Stanek A , Piotrowicz M , Waye JS , Utermann G , Krajewska‐Walasek M
Published: December 2004

Smith–Lemli–Opitz syndrome (SLOS) is an autosomal recessive disorder of cholesterol biosynthesis caused by mutations in the DHCR7 gene. Thirty‐seven ethnic Polish patients with SLOS underwent mutation analysis. The mutation frequencies in Polish patients were significantly different from those observed in Western European populations. Two mutations, W151X (22/68 alleles, 32%) and V326L (19/68 alleles, 28%), accounted for 60% of all observed in our cohort. Two missense mutations L68P and L360P have not been reported previously. In total, we report 15 DHCR7 mutations identified in Polish patients. By comparing clinical severity scores and the biochemical and molecular data, a genotype–phenotype correlation was attempted. In compound heterozygotes with one null mutation, the phenotype severity depends on the localization and type of the second mutation: mild phenotypes are correlated with mutations affecting the putative transmembrane domains TM1–TM6 or CT regions and severe phenotypes with mutations localized in TM7 and 4L region. The phenotypic differences of patients with the same genotype suggest that severity of the disease may be affected by other factors.
Health motivation and emotional vigilance in genetic testing for prostate cancer risk
Authors: Li Y , Doukas DJ
Published: December 2004

Actual uptake of genetic testing for cancer susceptibility is generally lower than 50%, despite a high initial interest above 80%. As population‐based genetic testing for cancer susceptibility becomes more widespread, there will be an increasing need to understand the relationship of patient‐affective factors to test intention and actual uptake behavior. Using hypothetical genetic testing for prostate cancer susceptibility as an example, we used surveys of 400 men in the general population of Philadelphia to develop a Structural Equation Modeling diagram to reveal the influence of affective factors implicated in the intention to undergo genetic testing for prostate cancer risk. Results showed that most men want genetic testing for prostate cancer, believe strongly in its benefits, and are not deterred by negative affect. Our data suggest that high positive expectations, plus a high desire to comply with physician and family suggestions, result in an increased test intention. Informed consent assessment, therefore, requires an appreciation not only of patient risk, but awareness of patient motivation and affect as well.
Chondrodysplasia punctata in siblings and maternal lupus erythematosus
Authors: Kozlowski K , Basel D , Beighton P
Published: December 2004

Chondrodysplasia punctata (CDP) was diagnosed clinically and radiographically in a male child born in Cape Town in 1991. His only sibling, a brother born in 2000 was similarly but more severely affected. The boys' mother had longstanding disseminated lupus erythematosus and epilepsy, for which she had been treated with chloraquine and other therapeutic agents during both pregnancies. The parents were non‐consanguineous, and the family history was unremarkable.

In addition to these affected brothers, seven previous instances of the association of CDP and maternal lupus erythematosus (MLE) have been reported. On this basis, MLE must be regarded as yet another causative factor in CDP.
Maternal mutation 677C > T in the methylenetetrahydrofolate reductase gene associated with severe brain injury in offspring
Authors: De Kremer R Dodelson , Grosso C
Published: December 2004

A frequent polymorphism in the gene coding for 5,10‐methylenetetrahydrofolate reductase is the substitution 677C > T which produces a thermolabile and inefficient enzyme. Homozygosity for the 677C > T allele is the most important determinant of hyperhomocys‐teinemia, when folic acid intake is reduced. Most studies on the relationship between the 677C > T variant in the mother and defects in the offspring have focused on neural‐tube defects. This study is a retrospective case‐control investigation of hypoxic‐ischemic encephalopathy of the newborn (HIEN) with reference to the 677C > T polymorphism as a genetic risk for this condition.

The prevalence of the 677C > T allele was studied in 11 children with HIEN, their respective mothers, and 85 healthy individuals. Plasma homocysteine levels after fasting and methionine loading were determined in both mothers and controls.

Ten of 11 patients were evaluated using magnetic resonance (MR) imaging, and all showed multicystic encephalomalacia and severe brain vasculopathy. Seven mothers were homozygous and four heterozygous for the 677C > T allele. Five of the children were homozygous and six heterozygous for this polymorphism. The variant allele frequency was higher in the group of mothers with affected children than in the controls and was associated with an increase in plasma homocysteine after methionine loading, in the group of mothers than in controls.

The 677C > T mutation in mothers, either in a homozygous or heterozygous state, together with poor nutritional status (probable folate deficiency) may represent a risk factor for irreversible HIEN in the offspring.
The endless quest for sex determination genes
Authors: Fleming A , Vilain E
Published: December 2004

Disorders in human sex determination cause defects in gonadal function and can result in a spectrum of abnormalities in the internal and external genitalia, ranging from relatively mild sexual ambiguities to complete sex reversal. Several genes involved in sex determination have been validated in humans, and activities of their gene products are being elucidated, particularly in mouse models. However, how these genes interact in an overall process remains far from clear, and it is probable that many additional genes are involved. Management of patients with pathologies in sex determination and subsequent differentiation is currently under debate, but will require not only an understanding of the multiple definitions of an individual's sex but also an increased knowledge of the molecular mechanisms involved in sex determination.
The Hunter–McAlpine syndrome results from duplication 5q35–qter
Authors: Hunter AGW , Dupont B , McLaughlin M , Hinton L , Baker E , Adès L , Haan E , Schwartz CE
Published: December 2004

In 1977 Hunter et al. J Med Genet 1977: 14 (6): 430–437, reported a family with six affected members, connected over three generations through unaffected individuals. Subsequently, several other patients purported to have the condition were reported. The condition became known as the Hunter–McAlpine syndrome, and there was debate as to whether or not it was identical to the Ruvalcaba syndrome or a type of tricho‐rhino‐phalangeal syndrome. In this article we confirm that the original family and a patient reported by Adés et al. Clin Dysmorphol 1993: 2 (2): 123–130 have cryptic translocations resulting in duplication of 5q35–qter. Similarities are noted between our patients and others in the literature with duplication of this chromosome segment.
Delayed occurrence of cardiac allograft vasculopathy in Chinese heart transplant recipients compared with their western counterparts
Authors: Wang Huang‐Joe , Ko Wen‐Je , Lee Chii‐Ming , Hsu Ron‐Bin , Chou Nai‐Kuan , Wang Shoei‐Shen , Liau Chiau‐Suong , Chu Shu‐Hsun , Lee Yuan‐Teh
Published: December 2004

Abstract:  Cardiac allograft vasculopathy (CAV) is a leading limiting factor to long‐term survival after cardiac transplantation. We investigated the prevalence of CAV and its associated factors in Chinese heart transplant recipients. From July 1987 to July 2000, we performed 140 consecutive heart transplantations at the National Taiwan University Hospital. Of the 140 patients, 98 who were 17‐yr old at the time of transplantation, had survived for more than 1 yr after transplantation, and who had normal findings at the 1‐month coronary angiogram study, were included in this study. Group I consisted of 25 patients who eventually developed CAV in the follow‐up, and group II consisted of 73 patients who were free from CAV in the follow‐up. CAV was defined by coronary angiogram study.The donor and recipient characteristics were not statistically different between the two groups except the older donor age (p = 0.02), higher first‐year mean rejection score (p = 0.03) and more prevalent cytomegalovirus infection rate (p = 0.03) in group I. Multivariate Cox regression analysis revealed that only higher first‐year mean rejection score (p = 0.01), and older donor age (p = 0.04) were important risk factors for developing CAV. The 1–5 yr of actuarial freedom from the presence of CAV were 97, 93, 86, 80 and 69% in our study patients. In summary, these data show that CAV occurred later in Chinese heart transplant recipients in comparison with their western counterparts, but the risk factors for developing CAV were not different.
Increasing medication access to transplant recipients
Authors: Chisholm Marie
Published: December 2004

Abstract:  Transplant recipients require numerous medications to maintain graft survival and health. Post‐transplant medication therapy costs greater than $12 000 annually, and the cost of therapy is expected to increase. Although medication costs continue to rise, a substantial portion of Americans lack adequate health insurance or do not have any insurance coverage. To facilitate health, it is imperative that health care providers are familiar with programs that are available to increase prescribed medication access to transplant recipients. The purpose of this manuscript is to provide an overview of common programs available to increase transplant recipients’ access to medications. In addition to discussing the consequences of medication non‐compliance, this manuscript reviews Medicare, Medigap, Medicaid, Qualified Medicare Beneficiaries, and pharmaceutical manufacturers’ medication assistance programs and its use to increase medication access to solid‐organ transplant recipients.
Tube thoracostomy during allogeneic stem cell transplantation does not carry an increased risk for infections or bleeding
Authors: Barkan D , Nusair S , Resnick IB , Bitan M , Segel MJ , Or R , Ackerstein A , Samuel S , Breuer R , Shapira MY
Published: December 2004

Abstract:  Background:  Candidates for stem cell transplantation may occasionally suffer from massive pleural effusions related to their disease and require tube thoracostomy. The additional risk of this procedure during allogeneic transplantation procedure is not known.

Methods:  Four high‐risk patients transplanted in our institution during a 2‐yr period had chest drainage by tube thoracostomy. The characteristics of the fluid, the clinical course, and the outcome were assessed.

Results:  A total of nine chest drains were inserted (range 1–5). No bleeding complications related to the procedure were noted. None of the patients developed any clinical signs of local infection at the tube insertion site or within the pleural fluid. All cultures taken from the drained fluid or from the insertion wound were negative.

Conclusions:  Tube thoracostomy in itself does not seem to pose additional risks in the transplant procedure, despite all patients in this series being considered to be at high‐risk for complications.
Monoclonal Antibodies Specific for Natural Human Neutrophil Gelatinase B Used for Affinity Purification, Quantitation by Two‐Site ELISA and Inhibition of Enzymatic Activity
Authors: Paemen Liesbet , Martens Erik , Masure Stefan , Opdenakker Ghislain
Published: December 2004

Human gelatinase B was produced from peripheral blood neutrophils and purified by affinity chromatography on gelatin sepharose. This material was used as an antigen to prepare mouse monoclonal antibodies (mAb). The resulting hybridomas were selected on the basis of binding to biotinylated antigen and by a sandwich ELSA using gelatinase‐B‐specific polyclonal rabbit antiserum and pure natural antigen. Five of these mAb were selected for further characterization. They all displayed variable epitope specificity, binding capacity and inhibitory activity. Whereas mAb REGA‐2D9 and REGA‐3G12 showed the strongest binding to biotinylated gelatinase B and natural gelatinase B, respectively, mAb REGA‐2F9 did not bind biotinylated antigen. None of the mAb displayed cross‐reactivity to gelatinase A in a direct ELISA. The mAb REGA‐1G8 was found to cross‐react with human serum albumin. The binding capacity of the other four mAb with leukocyte gelatinase B was compared and a sensitive sandwich ELISA was developed with the antibodies REGA‐3G12 and REGA‐2D9 (detection limit 0.5 ng/ml). The mAb REGA‐3G12 was unique in that it inhibited catalysis by gelatinase B. This was shown by assaying the degridation of nasal septum type II gelatin in the presence and absence of each of the five mAb. Furthermore, mAb REGA‐3G12 inhibited the degradation of biotinylated gelatin in a microtiterplate solution assay. In addition to the potential use of the inhibitory mAb REGA‐3G12 in the treatment of diseases with excessive gelatinase B production, several of the described mAb are useful as diagnostic probes to detect gelatinase B in body fluids and tissue samples of patients with multiple sclerosis. rheumatoid arthritis and cancer.
The Affinity and Specificity of Ca2+‐Binding Sites of Cytochrome‐c Peroxidase from Paracoccus Denitrificans
Authors: Gilmour Raymond , Prazeres Susana , Mcginnity Dermot F. , Goodhew Celia F. , Moura José J. G. , Moura Isabel , Pettigrew Graham W.
Published: December 2004

The binding of Ca2+ to the dihaem cytochrome‐c. peroxidase from Paracoccus denitrificans was analysed by following perturbations in the visible and 1H‐NMR spectra of both haem groups. The enzyme contains at least two types of Ca2+‐binding site. Site I is occupied in the isolated enzyme, binds Ca2+ with a redox‐state‐independent Kd of 1.2 μM and accommodates neither Mg2+ nor Mn2+. Site II is unoccupied in dilute solutions of the isolated oxidised enzyme and binds Ca2+ cooperatively with a Kd of 0.52 mM. In the mixed valence form, the binding affinity increases to resemble that of site I. The cooperativity was shown by ‐Ca2+ binding to site II, the titration of haem methyl 1H‐NMR resonances, and a half‐of‐sites effect observed for modification of an essential histidine with diethylpyrocarbonate. These are all consistent with site II being situated at the interface between two monomers of a dimeric enzyme. Thus the equilibrium of binding to site II is a reflection of the equilibrium for dimerisation and conditions which shift that equilibrium towards the dimer, such as increased ionic strength or high protein concentration, also increase Ca2+ affinity.

Binding of Ca2+ to site II is required for formation of the active high spin state at the peroxidatic haem.
The Tungsten Formylmethanofuran Dehydrogenase from Methanobacterium Thermoautotrophicum Contains Sequence Motifs Characteristic for Enzymes Containing Molybdopterin Dinucleotide
Authors: Hochheimer Andreas , Schmitz Ruth A. , Thauer Rudolf K. , Hedderich Reiner
Published: December 2004

Formylmethanofuran dehydrogenases are molybdenum or tungsten iron‐sulfur proteins containing a pterin dinucleotide cofactor. We report here on the primary structures of the four subunits FwdABCD of the tungsten enzyme from Methanobacterium thermoautotrophicum which were determined by cloning and sequencing the encoding genes fwdABCD. FwdB was found to contain sequence motifs characteristic for molybdopterin‐dinucleotide‐containing enzymes indicating that this subunit harbors the active site. FwdA, FwdC and FwdD showed no significant sequence similarity to proteins in the data bases. Northern blot analysis revealed that the four fwd genes form a transcription unit together with three additional genes designated fwdE, fwdF and fwdG. A 17.8‐kDa protein and an 8.6‐kDa protein, both containing two [4Fe‐4S] cluster binding motifs, were deduced from fwdE and fwdG. The open reading frame fwdF encodes a 38.6‐kDa protein containing eight binding motifs for [4Fe‐4S] clusters suggesting the gene product to be a novel polyferredoxin. All seven fwd genes were expressed in Escherichia coli yielding proteins of the expected size. The fwd operon was found to be located in a region of the M. thermoautotrophicum genome encoding molybdenum enzymes and proteins involved in molybdopterin biosynthesis.
Regulation of maize lysine metabolism and endosperm protein synthesis by opaque and floury mutations
Authors: Azevedo Ricardo A. , Damerval Catherine , Landry Jacques , Lea Peter J. , Bellato Cláudia M. , Meinhardt Lyndel W. , Le Guilloux Martine , Delhaye Sonia , Toro Alejandro A. , Gaziola Salete A , Berdejo Bertha D. A.
Published: December 2004

The capacity of two maize opaque endosperm mutants (o1 and o2) and two floury (fl1 and fl2) to accumulate lysine in the seed in relation to their wild type counterparts Oh43+ was examined. The highest total lysine content was 3.78% in the o2 mutant and the lowest 1.87% in fl1, as compared with the wild type (1.49%). For soluble lysine, o2 exhibited over a 700% increase, whilst for fl3 a 28% decrease was encountered, as compared with the wild type. In order to understand the mechanisms causing these large variations in both total and soluble lysine content, a quantitative and qualitative study of the N constituents of the endosperm has been carried out and data obtained for the total protein, nonprotein N, soluble amino acids, albumins/globulins, zeins and glutelins present in the seed of the mutants. Following two‐dimensional PAGE separation, a total of 35 different forms of zein polypeptides were detected and considerable differences were noted between the five different lines. In addition, two enzymes of the aspartate biosynthetic pathway, aspartate kinase and homoserine dehydrogenase were analyzed with respect to feedback inhibition by lysine and threonine. The activities of the enzymes lysine 2‐oxoglutate reductase and saccharopine dehydrogenase, both involved in lysine degradation in the maize endosperm were also determined and shown to be reduced several fold with the introduction of the o2, fl1 and fl2 mutations in the Oh43+ inbred line, whereas wild‐type activity levels were verified in the Oh43o1 mutant.