Complete maternal uniparental isodisomy of chromosome 4 in a subject with major depressive disorder detected by high density SNP genotyping arrays.

Uniparental isodisomy (iUPD) is a rare genetic condition caused by non-disjunction during meiosis that ultimately leads to a duplication of either the maternal or paternal chromosome in the affected individual. Two types of disorders can result, those due to imprinted genes and those due to homozygosity of recessive disease-causing mutations. Here, we describe the third known case of complete chromosome 4 iUPD of maternal origin. This condition became apparent during whole genome linkage studies of psychiatric disorders in the Portuguese population. The proband is an adult female with normal fertility and no major medical complaints, but a history of major depressive disorder and multiple suicide attempts. The proband's siblings and parents had normal chromosome 4 genotypes and no history of mood disturbance. A brief review of other studies lends support for the possibility that genes on chromosome 4 might confer risk for mood disorders. We conclude that chromosome 4 maternal uniparental disomy (UPD) is a rare disorder that may present with a major depressive phenotype. The lack of a common disease phenotype between this and two other cases of chromosome 4 iUPD [Lindenbaum et al. [1991] Am J Med Genet 49(Suppl 285):1582; Spena et al. [2004] Eur J Hum Genet 12:891-898) would suggest that there is no vital maternal gene imprinting on chromosome 4. However, since there is no reported case of paternal chromosome 4 UPD, paternal gene imprinting on chromosome 4 cannot be excluded.     

Inhibition of PAF-induced eosinophil accumulation in pulmonary airways of guinea pigs by anti-asthma drugs

Intraperitoneal (i.p.) injection of platelet activating factor (PAF) in guinea pigs caused a dose-related increase in the number of eosinophils recovered from bronchoalveolar lavage fluid (BALF). The prevalence of eosinophils in BALF had significantly increased within 1 hr of i.p. injection of PAF (10 micrograms/animal) and was maximal after 24 hr. Subcutaneous osmotic mini-pumps were used to administer drugs for 5 days prior to i.p. injection of PAF (10 micrograms/animal) and for the subsequent 24 hr. The percentage increase of eosinophils in BALF, due to PAF, was inhibited in animals treated with dexamethasone, aminophylline, cromoglycate, tranilast or ketotifen, but not in animals treated with oxatomide, azelastine, amlexanox, ibudilast or AA-861. These results suggest that inhibition of pulmonary eosinophilia may be a necessary property of prophylactic anti-asthma drugs and provide indirect evidence favoring a role for PAF in eosinophilia of asthma.     

Intracellular messengers and the control of protein synthesis

The molecular events responsible for controlling cell growth and development, as well as their coordinate interaction is only beginning to be revealed. At the basis of these controlling events are hormones, growth factors and mitogens which, through transmembrane signalling trigger an array of cellular responses, initiated by receptor-associated tyrosine kinases, which in turn either directly or indirectly mediate their effects through serine/threonine protein kinases. Utilizing the obligatory response of activation of protein synthesis in cell growth and development, we describe efforts to work backwards along the regulatory pathway to the receptor, identifying those molecular components involved in modulating the rate of translation. We begin by describing the components and steps of protein synthesis and then discuss in detail the regulatory pathways involved in the mitogenic response of eukaryotic cells and during meiotic maturation of oocytes. Finally we discuss possible future work which will further our understanding of these systems.     

A daily process design study of attentional pain control strategies in the self-management of cancer pain.

This study investigated the use of attentional control strategies in the self-management of pain using daily process design methodology. Twenty six cancer patients with pain completed diaries 3 times daily for 10 days. Diaries incorporated measures of pain intensity, affect, coping, coping efficacy, and the novelty and predictability of pain, and participants completed a cross-sectional measure of catastrophizing. At the across-person level, focusing on pain was associated with increased negative affect, and the use of pain focusing strategies was positively correlated with experiencing pain that was novel in its location or quality. Distractions that were interesting, important and pleasant were positively correlated with positive affect, perceptions of control over pain and ability to decrease pain. Over-prediction of pain was positively correlated with catastrophizing, and negatively correlated with perceptions of control over and ability to decrease pain. The within-person analysis (ARIMA modelling) showed that catastrophizing moderated the effects of pain focusing strategies, novel pain and over-predictions of pain. Meta-analysis of the ARIMA models revealed that the within-person effects of using attentional strategies did not generalize across the sample. These findings indicated that the effects of distraction strategies are influenced by their motivational-affective significance rather than the frequency with which they are used, and provided further evidence that the threat value of pain influences the way in which people cope with their pain. Theoretical and clinical implications are discussed.     

Effects of bombesin and gastrin-releasing peptide on memory processing

We have previously shown that feeding mice immediately following training enhances memory retention and that one of the gastrointestinal hormones released during a meal, cholecystokinin, also enhances retention after peripheral administration. In the studies reported here we demonstrate that another gastrointestinal peptide, gastrin-releasing peptide (GRP), enhances retention after peripheral administration, as does its amphibian counterpart, bombesin. GRP_14–27 had the same effect as the intact peptide, while GRP_1–16 was ineffective at enhancing retention. The dose-response curves showed a characteristic inverted U-shape with high doses of both GRP and bombesin being amnestic. The effect of both peptides was time-dependent and both reversed amnesia induced by the anticholinergic, scopolamine. I.c.v. administration of the peptides required higher doses to produce an effect on memory retention. suggesting that the effect was mediated predominantly through a peripheral mechanism. Doses of the peptides that enhanced memory retention after peripheral administration failed to increase serum glucose, suggesting that glucose modulation was not the mechanism by which GRP and bombesin modulate memory processing. Vagotomy inhibited the memory-enhancing effects of both GRP and bombesin, suggesting that these peptides produced their effect by stimulating ascending vagal pathways. These studies, together with our previous study with cholecystokinin, suggest the existence of a gastrointestinal hormonal system, which is activated by the passage of food through the intestine, that enhances memory retention.     

The uses of a patient-based dietetic data-collection systern

The F.I.P. (Financial Information Project) dietetic package allows the collection of basic patient data, which then can be processed to give valuable clinical and management information for use by all dietitians in a dietetic department. The advent of the Korner Reports (DHSS, 1984a) and their implementation highlighted the need to computerize certain aspects of data collection in dietetic departments. Within the West Midlands Regional Health Authority a group of dietitians worked with the Regional Management Services Department to adapt a community nursing system, F.I.P., for use by dietitians. The system was piloted for all paramedical services in 1987 with one health district (North Warwickshire) piloting the dietetic package. It is now used by a range of dietetic and paramedical departments. This paper outlines the system and its uses.     

A randomised trial of two methods of issuing prenatal test results: the ARIA (Amniocentesis Results: Investigation of Anxiety) trial

BACKGROUND: Many pregnant women experience anxiety while waiting for the results of diagnostic tests. Policies and practices intended to reduce this anxiety require evaluation. OBJECTIVES: To test the following two hypotheses: * That giving amniocentesis results out on a fixed date alters maternal anxiety during the waiting period, compared with a policy of telling parents that the result will be issued "when available" (i.e. variable date). * That issuing early results from a rapid molecular test alters maternal anxiety during the waiting period, compared with not receiving any results prior to the karyotype. The effects of the two interventions on anxiety 1 month after receiving karyotype results were also examined. DESIGN: A multicentre, randomised, controlled, open fixed sample, 2 x 2 factorial design trial, with equal randomisation. SETTING: The prenatal diagnosis clinics in 12 hospitals in England offering amniocentesis as a diagnostic test for Down's syndrome. SAMPLE: Two hundred and twenty-six women who had had an amniocentesis were randomised between June 2002 and July 2004. Eight women with abnormal results or test failure were excluded post-randomisation. INTERVENTIONS: Issuing karyotype results on a prespecified fixed date, rather than issuing them as soon as they became available. Issuing karyotype results alone, or subsequent to issuing results from a rapid molecular test for the most common chromosomal abnormalities. MAIN OUTCOME MEASURES: Average anxiety during the waiting period, calculated using daily scores from the short version of the Spielberger State-Trait Anxiety Inventory (STAI). Anxiety 1 month after receiving karyotype results, measured using the short form STAI. RESULTS: Issuing early results from a partial but rapid test reduced maternal anxiety by a clinically significant amount during the waiting period (mean daily score 12.5 versus 14.8; scale score difference -2.36, 95% CI -1.2, -3.6), compared with receiving only the full karyotype results. There was no evidence that giving out karyotype results on a fixed or on a variable date altered maternal anxiety during the waiting period (mean daily score 13.2 versus 14.2; scale score difference -1.02, 95% CI -2.2, 0.2). One month after receiving normal karyotype results, anxiety was low in all groups, but women who had been given rapid test results tended to be more anxious than those who had not (mean single day score 9.2 versus 8.3; mean scale score difference 0.95, 95% CI -0.03, 1.9). This small to moderate effect did not reach conventional levels of statistical significance. CONCLUSIONS: Rapid testing was a beneficial addition to karyotyping, at least in the short term. This does not necessarily imply that early results would be preferred to comprehensive ones if women had to choose between them. Because there are no clear advantages in anxiety terms of issuing karyotype results as soon as they become available, or on a fixed date, women could be given a choice between them.     

Transfer of clonidine and dexmedetomidine across the isolated perfused human placenta

Background: The placental transfer of the a₂ receptor agonist clonidine, earlier used as an adjuvant in obstetric epidural analgesia, was compared with the transfer of the newer and more %-selective agonist dexmedetomidine.
Methods: Term placentas were obtained immediately after delivery with maternal consent and a 2-hour recycling perfusion of a single placental cotyledon was performed. Disappearance from the maternal circulation, accumulation in placental tissue and appearance in the fetal circulation of clonidine or dexmedetomidine with the reference compound antipyrine were followed in 4 experiments for both drugs.
Results: At 2 hours the percent dexmedetomidine found in the fetal circulation was 12.5 (SD 5.1)%, while 48.1 (SD 20.3)% was found in the perfused placental cotyledon. A higher mean clonidine than dexmedetomidine concentration was achieved in the fetal circulation (1.90 vs. 0.56 nmol/l, P <0.05). At 2 hours the percent clonidine found in the fetal circulation was 22.1 (SD 2.4)% ( P <0.05), while 11.3 (SD 3.3)% ( P <0.05) was re tained in the perfused placental cotyledon. The transfer indexes, describing maternal-to-fetal transfer of dexmedetomidine and clonidine normalized with the transfer of antipyrine, were 0.88 (SD 0.07) and 1.04 (SD 0.08) respectively ( P <0.05).
Conclusions: Dexmedetomidine disappeared faster than clonidine from the maternal circulation, while even less dexmedetomidine was transported into the fetal circulation. This was due to its greater placental tissue retention, the basis for which probably is the higher lipophilicity of dexmedetomidine.