bluuebunny/crossref_metadata_2025 huggingface dataset:
A phylogenetic analysis of Tubificinae and Limnodriloidinae (Annelida, Clitellata, Tubificidae) using sperm and somatic characters
Authors: Marotta Roberto , Ferraguti Marco , Erséus Christer
Published: December 2004

Marotta, R., Ferraguti, M. & Erséus, C. (2003). A phylogenetic analysis of Tubificinae and Limnodriloidinae (Annelida, Clitellata, Tubificidae) using sperm and somatic characters. —Zoologica Scripta, 32, 255–278.

The spermatozoa and the sperm aggregates of 13 species belonging to four genera (Smithsonidrilus, Limnodriloides, Thalassodrilides, Doliodrilus) in the tubificid subfamily Limnodriloidinae (Annelida, Oligochaeta) were studied and compared with the spermatozoal patterns already described in the subfamily Tubificinae. Two characters considered exclusive for the Tubificinae were found in the more spermatologically variable Limnodriloidinae: the production of two kinds of spermatozoa, eusperm and parasperm, and the presence, in the spermathecae, of sperm aggregates formed by a combination of the two sperm types. A parsimony analysis was performed on the spermatozoal data of the species examined and compared with that based on the somatic characters of the same species: a critical revision of the already codified eusperm characters was carried out and the ultrastructure of parasperm was used as a new subset of spermatozoal characters. In a total evidence approach, a further parsimony analysis was run using a matrix combining both sets of characters. This analysis suggested that the double sperm line and the sperm aggregates composed of both eusperm and parasperm may well be homologous in tubificines and limnodriloidines. It thus supported the previous notion that Tubificinae and Limnodriloidinae are closely related and indicated that these subfamilies may be sister taxa.
Information provided by pairs of distantly affected relatives to search for genes involved in rare autosomal dominant diseases
Authors: GÉNIN E. , BELLIS G. , CLERGET‐DARPOUX F.
Published: December 2004

When dominant mutations of different genes may lead to the same disease, it is often difficult to detect in a particular patient which gene is involved. A strategy is to make genealogical extensions to find affected relatives that should have inherited the same mutation. In particular, for diseases with late age of onset or short survival time, only poor information may be obtained from close relatives of probands and it can be particularly efficient to make genealogical extensions to detect pairs of distantly related affected individuals. Such a pair of affecteds may provide information concerning the region of the genome where the mutated gene should map. Two situations may be encountered depending on whether or not prior information on the location of mutated genes involved in the disease are available. If we already know, from previous linkage studies, that a gene located in a given region R of the genome may be involved in the disease, the problem is then to confirm that it is indeed a mutation of this gene that is involved in the affected pair. Once the implication of a gene in region R has been confirmed the affected pair of relatives may give information to restrict the length of this region R. In this paper we discuss these two points by deriving analytically first the lod score expected and second the expected reduction of the length of the region where the mutation is suspected to map as a function of the number of meioses between the two affected individuals and of the polymorphism of the markers available in the region.
Optimal weighting scheme for affected sib‐pair analysis of sibship data
Authors: SHAM P. C. , ZHAO J. H. , CURTIS D.
Published: December 2004

Application of the affected sib‐pair method of linkage analysis to sibships with variable numbers of affected and unaffected members requires a scheme for weighting the contributions from the sibships in the calculation of an overall test statistic. Currently accepted weighting schemes are based on the concepts of independent pairs and Shannon information content. Here, we show that the weighting scheme with maximum power to detect linkage can be determined from the theoretical means and variances of the sibship contributions under the null and alternative hypotheses. We derive the theoretical means and variances of the contributions from different types of sibships under a generalized single locus model. We use these theoretical means and variances to obtain the optimal weights for a variety of single locus models, and compare the power of existing weighting schemes relative to the optimum. The results suggest that, under a range of plausible assumptions, optimal power is nearly obtained by weighting to all sibpairs equally, except those occuring in sibships with so many affected siblings (usually five or more) that the probability of parental homozygosity for the disease allele becomes substantial. A corollary is that, in affected sib‐pair analysis, the ‘informativeness’ of a sibship is more nearly proportional to the number of affected sib‐pairs than to the number of affected siblings, up to about five affected siblings.
REPORT on the Fifth International Workshop on Chromosome 9 held at Eynsham, Oxfordshire, UK, September 4–6, 1996
Authors: POVEY S. , ATTWOOD J. , CHADWICK B. , FREZAL J. , HAINES J. L. , KNOWLES M. , KWIATKOWSKI D. J. , OLOPADE O. I. , SLAUGENHAUPT S. , SPURR N. K. , SMITH M. , STEEL K. , WHITE J. A. , PERICAK‐VANCE M. A.
Published: December 2004

The Fifth International workshop on chromosome 9 comprised a gathering of 36 scientists from seven countries and included a fairly even distribution of interests along chromosome 9 as well as a strong input from more global activities and from comparative mapping. At least eight groups had participated in the goal set at the previous workshop which was to improve the fine genetic mapping in different regions of chromosome 9 by meiotic breakpoint mapping in allocated regions and this has resulted in some greatly improved order information. Excellent computing facilities were available and all contributed maps were entered not only into SIGMA (and thence submitted to GDB) but also into a dedicated version of ACEDB which can be accessed on the Web in the form of one of 28 slices into which the chromosome has been arbitrarily divided. It was generally agreed that the amount of data is now overwhelming and that the integration and validation of all data is not only unrealistic in a short meeting but probably impossible until the whole chromosome has been sequenced and fully annotated. Sequence‐ready contigs presented at the meeting totalled about 3 MB which is about one fiftieth of the estimated length. The single biggest barrier to integration of maps is the problem of non‐standard nomenclature of loci. In the past 2 workshops efforts have been made to compare traditional ‘consensus’ maps made by human insight (still probably best for small specific regions) with those generated with some computer assistance (such as SIGMA) and those generated objectively by defined computer algorithms such as ldb. Since no single form of map or representation is entirely satisfactory for all purposes the maps reproduced in the published version of the report are confined to one of the genetic maps, in which Genethon and older markers have been incorporated, a Sigma map of the genes as symbols together with a listing of known ‘disease’ genes on chromosome 9, and a revised assessment of the mouse map together with a list of mouse loci predicted to be on human chromosome 9. One of the 28 ACEDB slices is also shown to illustrate strengths and weaknesses of this approach. Workshop files include not only all maps available at the time but also details of loci and details of the meiotic breakpoints in the CEPH families (http://www.gene.ucl.ac.uk/scw9db.shtml).

This report and other information on chromosome 9 can be found on the chromosome 9 homepage at the URL: http://www.gene.ucl.ac.uk/chr9/
Genetic heterogeneity of glucose‐6‐phosphate dehydrogenase deficiency in south‐east Sicily
Authors: CITTADELLA R. , CIVITELLI D. , MANNA I. , AZZIA N. , DI CATALDO A. , SCHILIROA G. , BRANCATI C.
Published: December 2004

In order to explore the nature of glucose‐6‐phosphate dehydrogenase (G6PD) deficiency in south‐east Sicily, we have analysed the G6PD gene in 25 unrelated males with abnormal G6PD activity and/or electrophoretic mobility, by using the analysis of the appropriate PCR‐amplified fragment of DNA and subsequent digestion by appropriate restriction‐enzymes, looking for the presence of certain known G6PD mutations. We amplified the entire G6PD coding sequence into eight fragments, followed by single‐strand conformation polymorphism (SSCP) analysis and sequencing of those individual fragments that were found to be abnormal by SSCP. Through these methods we found a total of twelve G6PD Mediterranean variants with the association of a silent mutation 1311 (also known as polymorphic site Bcl I), one G6PD Mediterranean without this association, four G6PD A− Val 68 and two G6PD Santamaria and five G6PD Chatham. In a subject with normal activity a mutation was found in exon 5, designated as G6PD Sao Borja. This is the first report on the molecular analysis of G6PD mutations in Sicily and we have obtained evidence for four distinct classes of variants.
Segregation analysis of ovarian cancer using diathesis to include other cancers
Authors: ECCLES D. M. , FORABOSCO P. , WILLIAMS A. , DUNN B. , WILLIAMS C. , BISHOP D. T. , MORTON N. E.
Published: December 2004

Despite the recent cloning of BRCA1, BRCA2 and the mismatch repair genes, it will still be a long time before it is possible to specify any individual's risk for ovarian cancer based on her genotype. Most women concerned about their risk on the basis of one or two affected relatives do not belong to extensive ovarian cancer families. Risk calculations depend on a reliable genetic model for ovarian cancer derived, ideally, from the population from which an individual is drawn. We have carried out a segregation analysis using data collected from consecutive ovarian cancer patients in two different centres in the UK. Complex segregation analysis was carried out with the addition of diathesis as a separate parameter allowing other cancers, associated with ovarian cancer, to be taken into account. The use of diathesis in the derivation of this alternative model is described. Analysed under joint likelihood without diathesis, the gene frequency is 0·0028 and penetrance to age 70 years is 50%. This is in agreement with other published models. Incorporating diathesis into the model under joint likelihood gives similar parameters for a single locus model but gives the best fit with a two locus model where both genes are rare.
Extension of the Haseman–Elston method to multiple alleles and multiple loci: theory and practice for candidate genes
Authors: STOESZ M. R. , COHEN J. C. , MOOSER V. , MARCOVINA S. , GUERRA R.
Published: December 2004

The Haseman & Elston (1972) sibling‐pair regression method has been used to detect and estimate the variance contribution to observed values of a quantitative trait by allelic variation in specific candidate genes. The procedure was developed under a model with a single biallelic trait locus. This assumption does not hold for several known systems. In this paper we prove that for candidate gene analysis the Haseman–Elston procedure extends to the case of multiple trait loci, each possibly having more than two alleles. Simulation experiments comparing single‐locus to two‐locus models show that fitting the extended regression equations maintains nominal significance levels, but the power to detect linkage to trait variation is not improved by including additional loci. These results indicate that the original proposal is statistically robust to violations of the underlying genetic model. Practical issues associated with quantifying the relative variance contribution by individual loci are also discussed. Applications of the extended regression equations to lipoprotein(a) and high density lipoprotein cholesterol are given for illustration.
A likelihood ratio test for detecting patterns of disease‐marker association
Authors: MORRIS A. P. , WHITTAKER J. C. , CURNOW R. N.
Published: December 2004

A likelihood ratio test of disease‐marker association is proposed, based on the observation of marker alleles transmitted from parents to affected children. The proposed association test has the advantage of identifying the population pattern of disease‐marker association, differentiating between marker alleles that are positively and negatively associated with the disease. The power of the test for detecting association is evaluated and compared with three existing multi‐allelic tests for some specific disease‐marker association patterns. The power of the parametric tests depends crucially on the pattern of disease‐marker association. An over‐parameterised association model is less detrimental in terms of power than an under parameterised model.
The sib‐pair problem. . I. Affected pairs with parents. Constant penetrance models
Authors: EDWARDS J. H.
Published: December 2004

Affected sib pairs with typed but unaffected parents, conveniently termed foursomes, have become a major source of information on genetic susceptibility to common disease. So far most methods of analysis have been based on extensions of the single locus analyses developed, and successfully applied, to the mendelian disorders. However, unifactorial methods are not suited to multifactorial disorders. The power of methods of detecting linkage in the presence of more than one locus with one or more susceptibility alleles is considered.

The relevance of familial clustering to predicting the presence of loci with susceptibility or resistance alleles sufficiently frequent and effective to have an appreciable influence on population incidence is discussed. The mathematical problem of clustering due to numerous alleles of small effect was resolved by Pearson in 1901 in relation to claims that the mendelian model of an allele at a single locus determining a distinct phenotype was necessary to explain the familial concentrations that had been observed in several species. The apparent inconsistency between the mendelian and polygenic models was resolved by Fisher's demonstration in 1918 that there was no essential difference between these two extreme forms of phenotypic determination. Although constant penetrance models are unrealistic, and no longer necessary since Pearson's analysis, the assumption is implicit in most recent analyses and has the advantage of simplicity in providing a lower limit on the sample sizes necessary.
Linkage of microsatellites to the AGXT gene on chromosome 2q37.3 and their role in prenatal diagnosis of primary hyperoxaluria type 1
Authors: VON SCHNAKENBURG C. , WEIR T. , RUMSBY G.
Published: December 2004

Defects in the AGXT gene mapped to chromosome 2q37.3 cause primary hyperoxaluria type 1 (PH1), one of the inherited disorders of endogenous oxalate overproduction. In order to identify diagnostically useful linkage markers in this region of chromosome 2 we have typed three microsatellite loci mapping to the q37 region of chromosome 2 in 192 individuals from 30 families. They were additionally studied for mutations and polymorphisms in the AGXT gene. Maximum lod scores of 29·1, 22·8 and 15·8 were obtained for D2S140, D2S125 and D2S395 respectively at recombination fractions (theta) of 0·001, 0·015 and 0·02. Confidence intervals for recombination as determined by the ‘lod‐1 rule’ were 0·015, 0·05 and 0·06. Three recombinants were identified between AGXT and D2S125/D2S395, whereas no recombination between AGXT and D2S140 was observed. These data allow the calculation of the risk of incorrect prenatal diagnosis of PH1 based solely on linkage analysis with these extragenic markers.
DNA polymorphisms of apolipoprotein B in the population of Senegal
Authors: CHAUFFERT M. , LARGHERO J. , NGOHOU‐BOTUM K. , CISSE A. , CHEVENNE D. , TRIVIN F.
Published: December 2004

Three apolipoprotein B (apoB) genetic polymorphisms, the XbaI, MspI and EcoRI restriction fragment length polymorphisms (RFLPs), were analysed for 221 individuals in Senegal by polymerase chain reaction. Allelic frequency determination revealed that this population has 0.79 XbaI− (X−), 0.96 MspI+ (M+), and 0.89 EcoRI+ (E+). Major genotypes were X−/X− (0.62), M+/M+ (0.92) and E+/E+ (0.80). The XbaI allele frequency is different (p<10−9) from that in Caucasians (0.47) and from that in Mongoloids (0.98). Significant differences between Senegalese and Caucasians, and between Senegalese and Mongoloids were also observed for the EcoRI and MspI alleles of the apoB genes.
Variation in mutation rate and direction between tetranucleotide STR loci in human colorectal carcinomas
Authors: HOFF‐OLSEN P. , MELING G. I. , OLAISEN B.
Published: December 2004

Replication error (RER) is defined as mutation events in repetitive DNA segments. To investigate further the RER phenomenon and reveal any differences in mutation outcome between different short tandem repeat (STR) loci, we have investigated the somatic mutation rate and the size distribution of new tumour alleles in four tetranucleotide STRs in a large material of unselected colorectal adenocarcinomas. DNA was extracted from the blood and carcinomas of 217 patients. All blood/tumour pairs were analysed using the STRs HUMTHO1, HUMFES/FPS, HUMVWA31/A and HUMF13A1. Mutations are detected at all four loci. There are substantial differences in mutation rate and mutation direction (i.e. expansion versus contraction) between different STR loci. In all four STRs, the majority of events represent gain or loss of a single repeat. Almost all new tumour alleles correspond to known alleles in a population database, indicating that these are also composed of integers of the four base pair repeat. There is no statistically significant size bias in the mutating alleles as compared to the allelic distribution in the population database.
Missing data in haplotype analysis: a study on the MILC method
Authors: BOURGAIN C. , GENIN E. , OBER C. , CLERGET‐DARPOUX F.
Published: December 2004

Given the enormous progress in the knowledge of the human genome, genetic markers are now available throughout the genome. Haplotype analysis, allowing the simultaneous use of information from several markers, has thus become increasingly popular. However, we often face the problem of missing data and of haplotype identification. We have proposed a haplotype based method for the genetic study of multifactorial diseases in founder populations, the MILC method (Bourgain et al. 2000). MILC is based on the contrast of identity length between haplotypes transmitted to affected offspring and haplotypes non‐transmitted. In this study, the impact of different strategies, regarding missing data, on the MILC method are evaluated. A real situation is considered where data are derived from a genome screen for asthma susceptibility alleles in the Hutterites. Results are illustrated on this asthma data set.
Neurotransmitter release in an arterial preparation and the action of α‐adrenoceptor antagonists
Authors: Kalsner S. , Abdali S. A.
Published: December 2004

1 This study examined the potentiating effects of competitive antagonists of the adrenergic alpha2 receptors and of phenoxybenzamine (POB) an irreversible antagonist, on the stimulation‐induced efflux of [3H]‐noradrenaline in arterial tissue of rabbit. This was done to determine if the lack of concordance of efflux potentiation by antagonists with the expectations of presynaptic negative feedback theory can be attributed to increasingly successful competition from rising perineuronal transmitter concentrations, when stimulation parameters are increased, in the presence of a fixed concentration of competitive antagonist.

2 Tissues were stimulated with a fixed pulse number and frequency, to rule out confounding factors, and major alterations in the concentration of released transmitter were achieved through variations in the pulse duration.

3 Rauwolscine potentiated transmitter release less at the longest, rather than at the shortest pulse duration, and showed a potentiation of release that was indifferent to the quantities of released transmitter. This was also seen with POB although it binds covalently to the presynaptic receptor.

4 Noradrenaline inhibited stimulation‐induced transmitter release confirming the presence of presynaptic alpha inhibitory sites.

5 Yohimbine potentiated transmitter release the same as did rauwolscine and POB, and protected the relevant sites against POB potentiation, confirming site identity. The combination of POB and rauwolscine had no greater effect than did either alone certifying that they acted similarly and that maximally effective concentrations of each were used.

6 Consequently, noradrenaline breakthrough of presynaptic receptor blockade does not explain the non‐conforming observations made with competitive antagonists in tests of presynaptic theory.
Atenolol improves ventricular function without changing plasma noradrenaline but decreasing plasma atrial natriuretic factor in chronic heart failure
Authors: Gabrielli O. , Puyó A. M. , De Rosa A. , Armando I. , Barontini M. , Levin G.
Published: December 2004

1 There is good evidence that β‐blockers improve ventricular function, disease progression and survival in patients with left ventricular systolic dysfunction. The aim of this study was to determine the effects of atenolol therapy on the sympathetic nervous system at rest and after ergometric exercise, on left ventricular function and on baseline plasma atrial natriuretic factor (ANF) in ambulatory patients with chronic heart failure (CHF).

2 Twenty‐two patients [left ventricular ejection fraction (LVEF) <36%; New York Heart Association II–III] were studied before atenolol treatment. Because of cardiac events (new Hospital admission or death) only 13 patients completed 1 year of treatment. Baseline noradrenaline (NE) concentrations were similar in patients and controls while ANF was higher in patients than in controls (328 ± 35 pg ml−1vs. 37 ± 3 pg ml−1; P < 0.01).

3 Patients with events showed higher NE (540 ± 87 pg ml−1vs. 303 ± 44 pg ml−1; P < 0.01) and ANF (460 ± 70 pg ml−1vs. 291 ± 44 pg ml−1; P < 0.03) at rest; and greater NE response to exercise (2.003 ± 525 pg ml−1vs. 694 ± 121 pg ml−1; P < 0.005). Atenolol treatment improved LVEF (19.5 ± 1.9%vs. 33 ± 3.9%; P < 0.001), increased exercise tolerance (9 ± 3.2 min vs. 17 ± 4.8 min; P < 0.001) and decreased plasma ANF (292 ± 42 pg ml−1vs. 133 ± 35 pg ml−1; P < 0.01).

4 Reduced basal dihydroxyphenylglycol (DHPG)/NE ratio (3.4 ± 0.46 vs. 4.3 ± 0.35; P < 0.01) was observed in patients compared with healthy volunteers. Atenolol increased DHPG plasma levels (1.398 ± 129 pg ml−1vs. 913 ± 86 pg ml−1; P < 0.005) but the DHPG/NE ratio during exercise was not modified after treatment, suggesting that re‐uptake of released NE is not changed by β‐blocker treatment.

5 In conclusion, the fact that atenolol treatment improves ventricular dysfunction and clinical status without changing plasma NE levels in CHF patients, suggests that plasma NE is a poor surrogate measurement for cardiac sympathetic activity in this pathology. In addition, decrease in plasma ANF produced by atenolol treatment may reflect the improvement of ventricular function.
Histamine receptor type coupled to nitric oxide‐induced relaxation of guinea‐pig nasal mucosa
Authors: Bockman C. S. , Zeng W.
Published: December 2004

1 The aim of this study was to characterize the histamine receptor type mediating relaxation of the vascular bed of the nasal mucosa from the guinea‐pig, and to determine the role of cyclo‐oxygenase products and nitric oxide in this relaxant response to histamine. These studies were performed in isolated nasal mucosae examined in vitro to obtain potencies of histamine receptor‐type selective agonists in causing vasorelaxation and to determine affinities of histamine receptor antagonists for inhibiting histamine‐induced relaxation.

2 After contraction of nasal mucosae with noradrenaline, histamine caused a maximal relaxation response that was 75 ± 6% of the contraction caused by noradrenaline with a mean EC50 value of 4.3 ± 0.5 μm. Neither dimaprit (H2‐receptor selective) nor R‐α‐methylhistamine (H3‐receptor selective) caused significant relaxation of nasal mucosae. In contrast, betahistine (H1‐receptor selective) caused an 81 ± 7% relaxation of noradrenaline‐induced tone with an EC50 value of 15 ± 1 μm.

3 pA2 experiments were performed to obtain KB values of chlorpheniramine (H1‐receptor selective) and diphenhydramine (H1‐receptor selective) for blocking histamine‐stimulated relaxation of nasal mucosae. KB values for chlorpheniramine (0.87 nm) and diphenhydramine (7.4 nm) were consistent with their interaction at the H1‐receptor type. Additionally, neither 10 μm cimetidine (H2‐receptor selective) nor 1 μm thioperamide (H3‐receptor selective) had any effect on the relaxation curve for histamine.

4 In the presence of 10 μm indomethacin (cyclo‐oxygenase inhibitor), histamine caused a maximal relaxation response of 73 ± 5% of the noradrenaline‐induced tone with an EC50 value of 2.9 ± 0.2 μm, which was not different from control values (EC50 = 5.0 ± 0.4 μm; maximal relaxation = 71 ± 6%). In contrast, 200 μm NG‐nitro‐l‐arginine (nitric oxide synthase inhibitor) completely inhibited histamine‐induced relaxation of nasal mucosae.

5 In conclusion, data from the present study suggest only the H1‐receptor type mediates relaxation of nasal mucosal blood vessels to histamine, and histamine‐induced relaxation of nasal mucosae is entirely dependent on nitric oxide production.
Effects of lipopolysaccharide on vascular reactivity and mortality in rats
Authors: Nunes J. P. L.
Published: December 2004

1 The effects of intraperitoneal (i.p.) lipopolysaccharide on vascular reactivity to noradrenaline in rat aorta under different conditions of passive tension, as well as on mortality in normotensive and hypertensive rats, were studied.

2 Concentration–response curves to noradrenaline were obtained in aorta rings, at two levels of passive tension: 3 and 0.5 g, from control and lipopolysaccharide‐treated Wistar rats. Contractile responses were expressed as percentage of the maximal response to noradrenaline obtained in the beginning of the experiment at a resting tension of 2 g. The maxima were significantly larger (P < 0.05) at 3 g than at 0.5 g in both groups of rats: 117.8 vs. 62.3%, respectively, for control animals; 85.8 vs. 32.5%, respectively, for lipopolysaccharide‐treated rats.

3 The 24‐h mortality after the i.p. administration of lipopolysaccharide was lower in spontaneously hypertensive rats (1/12; 8%), when compared with control Wistar–Kyoto rats (5/11; 45%). However, mortality was higher in Wistar–Kyoto made hypertensive by 8‐day administration of corticosterone (6/6; 100%).

4 We conclude that a differential sensitivity to noradrenaline of aortic smooth muscle at two different levels of passive tension is still present in lipopolysaccharide‐treated animals. Chronic hypertension in SHR rats is associated with resistance to the lethal effects of lipopolysaccharide, whereas abrupt‐onset hypertension induced by corticosterone leads to an increased mortality.

5 These results are compatible with the myofibrillary hypothesis, which explains vascular hyper‐reactivity in chronic arterial hypertension, by postulating that a more favourable relative position (and/or proportion) for actin and myosin occurs, whereas in states of vascular hypo‐reactivity, such as vasodilatory shock, the opposite phenomenon may exist.
Alpha2‐adrenoceptor and NO mediate the opioid subsensitivity in isolated tissues of cholestatic animals
Authors: Demehri S. , Samini M. , Namiranian K. , Rastegar H. , Mehr S. E. , Homayoun H. , Roushanzamir F. , Jorjani M. , Dehpour A. R.
Published: December 2004

1 Our previous report showed that in acute cholestasis, the subsensitivity to morphine inhibitory effect on electrical‐stimulated contractions develops significantly faster in guinea‐pig ileum (GPI) and in mouse vas deferens (MVD) (45.2 and 29.9 times, respectively) compared with non‐cholestatic subjects.

2 The possible contribution of α2‐adrenoceptor and nitric oxide (NO) pathways on the development of tolerance was assessed in GPI and MVD of cholestatic subjects.

3 Daily administration of naltrexone (20 mg kg−1), yohimbine (5 mg kg−1), and Nω‐nitro‐l‐arginine methyl ester (l‐NAME) (3 mg kg−1) to cholestatic animals significantly (P‐value < 0.05) inhibited the process of subsensitivity in all groups.

4 Consistent with the literature, it was concluded that both the α2‐adrenergic system and NO have close interaction with the opioid system and may underlie some of the mechanisms involved in the subsensitivity development to opioids in acute cholestatic states.
Tumour necrosis factor‐alpha‐ vs. growth factor deprivation‐promoted cell death: different receptor requirements for mediating nerve growth factor‐promoted rescue
Authors: Pappas Todd C. , Decorti Francesco , Macdonald Nancy J. , Neet Kenneth E. , Taglialatela Giulio
Published: December 2004

Physiological and pathological aging of the central nervous system (CNS) is characterized by functional neuronal impairments which may lead to perturbed cell homeostasis and eventually to neuronal death. Many toxic events may underlie age‐related neurodegeneration. These include the effects of beta amyloid, Tau and mutated presenilin proteins, free radicals and oxidative stress, pro‐inflammatory cytokines and lack of growth factor support, which can be individually or collectively involved. Taken individually, these toxicants can induce very diverse cell responses, thus requiring individually targeted corrective interventions upstream of common cell death (apoptotic) pathways. Recent preliminary evidence suggests that the pro‐inflammatory cytokine tumour necrosis factor alpha (TNFα) and growth factor withdrawal can both activate a common apoptotic pathway in nerve growth factor (NGF)‐responsive PC12 cells involving caspase 3, albeit through very distinct upstream pathways: the former through active signalling and the latter through passive or lack of survival signalling. Here, we show that NGF can rescue PC12 cells from both growth factor withdrawal‐ and TNFα‐promoted cell death. However, NGF rescue from growth factor withdrawal requires NGF signalling through the high‐affinity tyrosine kinase receptor (TrkA), while NGF rescue from TNFα‐promoted cell death requires NGF signalling through the low‐affinity p75NTR receptor. These results strengthen the idea that prevention of age‐ or pathology‐associated neurodegeneration may require varied molecular approaches reflecting the diversity of the toxicants involved, possibly acting simultaneously.
Transcriptional outputs of the Caenorhabditis elegans forkhead protein DAF‐16
Authors: McElwee Joshua , Bubb Kerry , Thomas James H.
Published: December 2004

In Caenorhabditis elegans, the forkhead protein DAF‐16 transduces insulin‐like signals that regulate larval development and adult lifespan. To identify DAF‐16‐dependent transcriptional alterations that occur in a long‐lived C. elegans strain, we used cDNA microarrays and genomic analysis to identify putative direct and indirect DAF‐16 transcriptional target genes. Our analysis suggests that DAF‐16 action regulates a wide range of physiological responses by altering the expression of genes involved in metabolism, energy generation and cellular stress responses. Furthermore, we observed a large overlap between DAF‐16‐dependent transcription and genes normally expressed in the long‐lived dauer larval stage. Finally, we examined the in vivo role of 35 of these target genes by RNA‐mediated interference and identified one gene encoding a putative protease that is necessary for the daf‐2 Age phenotype.
Mitochondria and aging: a role for the permeability transition?
Authors: Crompton M.
Published: December 2004

When mitochondria are subjected to oxidative stress and relatively high [Ca2+], they undergo a ‘permeability transition’ in which the inner membrane becomes freely permeable to low‐molecular‐weight solutes. This phenomenon reflects reversible deformation of the adenine nucleotide translocase, the loss of its native gating properties and the stabilization of the deformed state by cyclophilin‐D. The permeability transition may be a factor in cell dysfunction associated with aging. This can manifest in a number of ways ranging, in the most severe, from impaired energy transduction and compromised viability to more subtle influences on the propagation of Ca2+ signals. This article critically examines data relevant to this issue.
Oxidative stress and mitochondrial function with aging – the effects of calorie restriction
Authors: Merry B. J.
Published: December 2004

Accumulated oxidative stress resulting from a gradual shift in the redox status of tissues is now considered to be a key mechanism underlying the aging process. Calorie‐restricted (CR) feeding, an experimental protocol to extend survival and delay aging in rodents, is recognized to slow the rate of accrual of age‐related oxidative stress. This conclusion is based on the increase in tissues with age of the oxidation products of proteins, lipids and DNA. The functional consequence, however, of the accumulation of these non‐specific oxidative markers is more difficult to determine. A shift in the redox status of tissues with age and calorie restriction feeding may have a greater impact on cell function through activation of redox sensitive transcription factors than through the accumulation of these non‐specific oxidative markers. Activation of such transcription factors will stimulate signalling pathways that will lead to a change in the gene expression profile and cell functioning. Little research has been conducted in this area. It has been proposed that CR feeding slows the rate of accrual of oxidative damage because mitochondria in these animals have a lower rate of superoxide generation when compared with mitochondria from control animals. This proposal is based on in vitro observations using isolated mitochondria and clearly requires further confirmation in isolated cells or using an in vivo approach. The application of metabolic control analysis to identify in isolated mitochondria the mechanism underlying this response has suggested one possible explanation for the lower superoxide production rates observed.
Do olfactory reference syndrome and Jiko‐shu‐kyofu (a subtype of Taijin‐kyofu) share a common entity?
Authors: Suzuki K. , Takei N. , Iwata Y. , Sekine Y. , Toyoda T. , Nakamura K. , Minabe Y. , Kawai M. , Iyo M. , Mori N.
Published: December 2004

Objective:  Olfactory reference syndrome (ORS) in the Western literature is characterized as preoccupation with the idea that the body emits a foul odor. Japanese patients with a feature similar to ORS have long been recognized as jiko‐shu‐kyofu, which is believed to be a culture‐bound syndrome and specific to Japan. The aim of the study was to clarify the relationship between the two separate syndromes that had independently been recognized in culturally different settings.

Method:  The phenomenology and treatment of seven patients with jiko‐shu‐kyofu were described. A feature of jiko‐shu‐kyofu was then compared with that of ORS.

Results:  In our cases, clinical characteristics of jiko‐shu‐kyofu such as symptomatology, insight, and pharmacotherapy response were found identical to those of ORS except for the onset at relatively younger ages.

Conclusion:  Jiko‐shu‐kyofu and ORS may share a common clinical entity, hence the former is not a culturally distinctive disorder.
Psychotic disorders and gonadal function: evidence supporting the oestrogen hypothesis
Authors: Huber T. J. , Borsutzky M. , Schneider U. , Emrich H. M.
Published: December 2004

Objective:  The aim of this study was to further evaluate the oestrogen hypothesis of schizophrenia, which postulates low oestradiol levels to be a risk factor for these disorders. A possible influence of neuroleptic‐induced hyperprolactinaemia was to be addressed.

Method:  Sex hormones were measured and cycle phase assessed in 50 acutely psychotic women on admission and for four consecutive weeks as well as in three control groups.

Results:  Psychotic women were more likely to be admitted during a low oestrogen phase of their cycle and exhibited markedly reduced oestradiol levels, compared with 23 healthy controls, as well as 50 women suffering from other psychiatric disorders. Oestradiol variability was reduced over the menstrual cycle in women suffering from psychotic disorders.

Conclusion:  These results support the oestrogen hypothesis. Hyperprolactinaemia due to neuroleptic treatment does not appear to account for the findings.
Is the season of birth association with psychosis due to seasonal variations in foetal growth or other related exposures? A cohort study
Authors: Fouskakis D. , Gunnell D. , Rasmussen F. , Tynelius P. , Sipos A. , Harrison G.
Published: December 2004

Objective:  To investigate the association between season of birth and psychosis, and to assess whether any association is caused by seasonal fluctuations in foetal growth or other related exposures.

Method:  Cohort of 747 432 Swedish males and females born between 1973 and 1980 and followed up from 16 years of age to 31 December 1999. Psychiatric admissions were identified using the Swedish Inpatient Discharge Register. The analysis is based on the 696 025 subjects with complete data.

Results:  A total of 506 (0.07%) subjects developed schizophrenia and 879 (0.13%) non‐affective non‐schizophrenic psychoses. There was a moderate increased risk of schizophrenia amongst winter births, hazard ratio 1.23 (95% confidence interval 0.96–1.59), but this did not reach conventional levels of statistical significance. There was no association with non‐affective psychoses. We found no evidence that associations were confounded by measures of foetal growth or maternal socioeconomic position. There was no evidence that seasonal effects on schizophrenia differed in men and women.

Conclusion:  Season of birth associations with schizophrenia do not appear to be confounded by birth‐related exposures.
Studying personality characteristics in bipolar depressed subjects: how comparator group selection can dictate results
Authors: Parker G. , Parker K. , Malhi G. , Wilhelm K. , Mitchell P.
Published: December 2004

Objective:  To examine the extent to which identification of any distinct personality characteristics in bipolar subjects are influenced by selection of the comparison diagnostic group.

Method:  Scores were compared on several general measures of personality style and, additionally, the prevalence of disordered personality functioning was examined in a sample of 198 non‐psychotic depressed subjects, 39 with bipolar depression and 159 with unipolar depression.

Results:  When the bipolar subjects were separately compared with unipolar subjects, and to sub‐sets of those with clinically and DSM‐IV defined melancholic and non‐melancholic depression, quite differing results were suggested. In essence, clinically‐defined melancholic subjects had the least personality psychopathology in comparison with the non‐melancholic and bipolar subjects.

Conclusion:  Whether subjects with bipolar disorder have any distinct personality characteristics or over‐represented co‐morbid personality disorders remains quite unclear when reference is made to the literature. We suggest that inconsistencies across studies may reflect choice and representation of depressive sub‐types within the unipolar comparator group.
Relapse prevention by citalopram in SAD patients responding to 1 week of light therapy. A placebo‐controlled study
Authors: Martiny K. , Lunde M. , Simonsen C. , Clemmensen L. , Poulsen D. L. , Solstad K. , Bech P.
Published: December 2004

Objective:  We have tested the relapse‐preventive effect of citalopram when compared with placebo in 282 patients with Seasonal Affective Disorder (SAD) responding to 1 week of light therapy.

Method:  The response rate to 1‐week light therapy and relapse during the continuation phase of 15 weeks were assessed by use of the Hamilton Depression Rating Scale (HAM‐D17), the six‐item subscale (HAM‐D6), the Melancholia Scale (MES), and the combined HAM‐D/SIGH‐SAD.

Results:  The response rate to light therapy was 62.5% on the HAM‐D17 and the HAM‐D6, 56.1% on the HAM‐D/SIGH‐SAD, 52.8% on the MES. In the continuation phase, citalopram was found superior to placebo on all scales, but the difference was only of statistical significance on the HAM‐D6 and the MES. Mean citalopram dose was 26.3 mg.

Conclusion:  Light therapy was found to have and early onset of action. On the HAM‐D6 and the MES citalopram significantly reduced the relapse rate in the continuation phase.
An investigation of the prototype validity of the borderline DSM‐IV construct
Authors: Johansen M. , Karterud S. , Pedersen G. , Gude T. , Falkum E.
Published: December 2004

Objective:  To investigate the prototype validity of the borderline personality disorder (BPD) DSM‐IV construct.

Method:  Patients (n = 930) from the Norwegian Network of Psychotherapeutic Day Hospitals. Exploratory/confirmatory factor analyses, correlation and reliability statistics, chi‐square, and frequency distributions.

Results:  Number of BPD criteria showed no distinct threshold between No‐BPD and BPD patients among whom 136 different combinations of criteria occurred. Both factor analyses supported that one component/latent variable accounted for the variance of the BPD criteria, showing a high convergent and discriminant validity. The criterion of unstable relationships displayed the highest diagnostic efficiency, and that of chronic feelings of emptiness the lowest.

Conclusion:  The prototype theoretical model for BPD fitted the data well and appeared to be satisfactory described by the current criteria. The emptiness criterion needs a more appropriate definition and the hierarchy of the criteria in DSM‐IV should be revised.
Relapse into mania or depression following lithium discontinuation: a 7‐year follow‐up
Authors: Cavanagh J. , Smyth R. , Goodwin G. M.
Published: December 2004

Objective:  We aimed to assess whether outcome followed a worse course after acute lithium withdrawal.

Method:  Data were acquired by review of the clinical records on 14 cases and 28 controls matched for age, gender and time on lithium for about 7 years following discontinuation.

Results:  Significant differences were found between cases and controls. Cases experienced more episodes of depression and total affective relapse. The log‐rank test revealed a significantly lower survival probability in cases than controls (P < 0.0009). However, the increased risk of recurrence was largely confined to the interval immediately after lithium discontinuation.

Conclusion:  These results confirm that acute discontinuation of lithium leads to a high immediate relapse rate. Most of the excess morbidity over 7 years appears to be attributable to the first episode following discontinuation. Outcome was not worsened by discontinuation.
Actively cooled plasma electrode for long pulse operations in a cesium-seeded negative ion source
Authors: Fujiwara Yukio , Watanabe Kazuhiro , Okumura Yoshikazu , Trainham Rusty , Jacquot Claude
Published: December 2004

An actively cooled plasma electrode has been developed for long pulse operation in a cesium-seeded negative ion source. To keep the electrode temperature at about 300°C, which is the optimum range of temperature to enhance cesium effects, the electrode cooling structure has been designed using three-dimensional numerical simulation assuming that the heat flux from the source plasma was 15W∕cm2. Water cooling tubes were brazed to the plasma electrode substrate with spacers made of stainless steel, which acts as a thermal resistance. The fabricated plasma electrode has been tested in a cesium-seeded volume negative ion source called Kamaboko source. The temperature of the electrode reached 280°C for the arc power of 41kW, which is the operating condition required for producing D− beams with current densities exceeding 20mA∕cm2. It was demonstrated that the actively cooled plasma electrode is applicable to long pulse operations, meeting the temperature requirement for optimizing the surface-production process of negative ions in the cesium-seeded ion source.
Creation of plasma density transitions short compared to the plasma skin depth
Authors: Thompson M. C. , Rosenzweig J. B. , Travish G.
Published: December 2004

A plasma based electron beam source apparatus is described which creates a plasma with two distinct density regions separated by a transition which is shorter than the plasma skin depth kp−1 of either region. This sharp density modulation is achieved by using a perforated stainless steel screen to filter half of a diffusing plasma column. A simple physical model predicts that the length of the plasma density transition will vary with the distance from the screen. For a weakly magnetized plasma, the transition length will be twice the distance, on a line normal to the screen plane, from the screen edge to the location where the transition is measured. The plasma column is generated using an argon discharge plasma source. It has a peak density of approximately 3.5×1013cm−3 and a full width half maximum width of 5 cm. The discharge source utilizes a 7.5 cm diameter LaB6 disk cathode heated to 1300 °C using a graphite heater. The plasma column is filtered with a 78μm thick stainless steel sheet with 152μm holes and 21% open area. Plasma density transitions with lengths between 0.74 and 0.95kp−1 were measured.
Tomographic reconstruction of Hα emissivity profiles in HANBIT magnetic mirror device
Authors: Yoon Jung-Sik , Seo Dong-Cheol , Na Hoon-Kyun
Published: December 2004

Hydrogen is the main constitute of plasmas in HANBIT magnetic mirror device, therefore, measurement of the emission from excited levels of hydrogen atoms is an important diagnostic tool. From the emissivity of Hα radiation one can derive quantities such as the neutral hydrogen density and the source rate, i.e., the rate at which the plasma protons are replenished by ionization of neutral atoms diffusing into the plasma. The reconstruction of emissivity profiles from Hα radiation measurement is a highly undetermined and ill-posed inversion problem, due to the restricted viewing access, number of chords and the increased noise level. An unbiased and consistent probability theory based approach within the framework of Bayesian inference is provided by the maximum entropy method which is independent of model assumptions, but allows any prior knowledge available to be incorporated. The formalism is applied to the reconstruction of Hα emissivity profiles in HANBIT magnetic mirror device.
New technique deducing plasma potential by a capacitive coupling method in spraying dielectric barrier discharge plasmas
Authors: Choi Yong-Sup , Chung Kyu-Sun , Jung Yong Ho , You Hyun-Jong , Lee Myoung-Jae
Published: December 2004

A new method to measure the plasma potential in an atmospheric dielectric barrier discharge (DBD) plasmas is developed for a new spraying DBD plasma source, which is sustained by electric fields generated by flowing plasmas at the outer region of the electrodes, since conventional electric probe can not be applied due to arcing. The new technique is to measure the spatially averaged plasma potential by using a capacitive coupling method with calculation of collisional sheath thickness.