Mild learning difficulties and offending behaviour--is there a link with monoamine oxidase A deficiency?

We have attempted to replicate the findings of Brunner et al., who described a large Dutch kindred where several males were of borderline intelligence and showed characteristically aggressive and sometimes dangerous or extremely antisocial behaviour. The genetic defect for this syndrome was assigned to the p11-p21 region of the X chromosome following linkage analysis in a single kindred.

Identification of a transactivation motif in the CLN3 protein.

A transactivation motif has been identified in the neurodegenerative disease protein, CLN3. The C-terminal domain (residues 394-438) of CLN3 can function as a transcriptional activator when fused to the DNA binding domain, LexA. A series of deletion and substitution constructs have been generated to identify the essential region for transactivation.

Prevalence, causes and correlates of traumatic dental injuries among 13-year-olds in Brazil.

A cross-sectional survey was carried out. This involved 652 out of a total of 764 (85%) 13-year-old adolescents enrolled in private and public schools located in urban areas in Cianorte, Brazil. They were interviewed and examined for traumatic dental injuries by one trained examiner (B.

Proteome and glycosylation mapping identifies post-translational modifications associated with aggressive breast cancer.

Changes in glycosylation of glycoproteins and glycolipids is a common feature of cancer and may influence cancer cell behaviour, perhaps by enabling cell-cell interactions which favour metastasis or by allowing cancer cells to evade immuno-surveillance. Studies to identify glycosylation changes in human cancer have often used immunohistochemical techniques with lectins or antibodies and human tissue sections. Whilst some detailed biochemical studies have been performed there are few clinically relevant studies since the numbers of specimens evaluated are often very small.

GPs' views on their management of sexual dysfunction.

Background: Sexual dysfunction is an important aspect of sexual heath that is prevalent in the population but frequently goes undetected.

Objective: The aim of this study was to investigate the role of the GP in the management of problems of sexual dysfunction.

Methods: A postal questionnaire was sent to the 218 GPs on the Camden and Islington Health Authority List.

Direct thrombin inhibition reduces lung collagen, accumulation, and connective tissue growth factor mRNA levels in bleomycin-induced pulmonary fibrosis.

Dramatic activation of the coagulation cascade has been extensively documented for pulmonary fibrosis associated with acute and chronic lung injury. In addition to its role in hemostasis, thrombin exerts profibrotic effects via activation of the major thrombin receptor, protease-activated receptor-1. In this study, we examined the effect of the direct thrombin inhibitor, UK-156406 on fibroblast responses in vitro and on bleomycin-induced pulmonary fibrosis in rats.

Mitochondria and degenerative disorders.

In mammalian cells, mitochondria provide energy from aerobic metabolism. They play an important regulatory role in apoptosis, produce and detoxify free radicals, and serve as a cellular calcium buffer. Neurodegenerative disorders involving mitochondria can be divided into those caused by oxidative phosphorylation (OXPHOS) abnormalities either due to mitochondrial DNA (mtDNA) abnormalities, e.

IGF status is altered by tamoxifen in patients with breast cancer.

Aims: An increased concentration of insulin-like growth factor 1 (IGF-1) is an independent risk factor for premenopausal breast cancer. Tamoxifen is thought initially to reduce concentrations of IGF-1 and increase concentrations of the IGF binding proteins. The aim of this study was to compare concentrations of IGF-1, IGF binding protein 1 (IGF-BP1), and IGF-BP3 in patients with breast cancer (n = 14) with those seen in control subjects (n = 23) and to assess the effect of tamoxifen on IGF status in these patients.

Prospects for phosphoinositide 3-kinase inhibition as a cancer treatment.

The phosphoinositide 3-kinases (PI3-kinases) are a family of lipid kinases that have a key role in the regulation of many cellular processes including proliferation, survival, carbohydrate metabolism, and motility. There is now strong evidence that some members of the PI3-kinase family have an important role in cancer. Emerging evidence for functional specialisation of PI3-kinase isoforms suggests that isoform selective inhibitors, in contrast to the existing non-selective inhibitors wortmannin and LY294002, may prove to be useful anticancer drugs.

Interleukin-6 gene -174g>c and -572g>c promoter polymorphisms are strong predictors of plasma interleukin-6 levels after coronary artery bypass surgery.

Interleukin-6 (IL-6) synthesized in response to diverse stimuli may play an important role in bridging the inflammatory and atherosclerotic processes. The acute-phase response after coronary artery bypass graft surgery (CABG) is associated with the induction and release of cytokines, such as IL-6. We have examined the effect of common polymorphisms in the IL-6 gene promoter (-174G>C, -572G>C, and -597G>A) on IL-6 levels after elective CABG.

Age-related effects of genetic variation on lipid levels: The Columbia University BioMarkers Study.

Objectives: To examine the genotype:phenotype association in children compared with their parents.

Methods: Variations at 4 key gene loci, namely lipoprotein lipase (LPL S447X), hepatic lipase (HL -480C>T), cholesteryl ester transfer protein (CETP TaqIB), and apolipoprotein CIII (APOC3 -455T>C and -482C>T), were examined in children (n = 495) and their parents (n = 353) in the Columbia University BioMarkers Study, 1994 to 1998.

Results: The frequencies of the rare alleles of the HL -480C>T and APOC3 -455T>C and -482C>T (but not LPL S447X or CETP TaqIB) were significantly lower in non-Hispanic white participants compared with Hispanics.

Social deprivation and traumatic dental injuries among 14-year-old schoolchildren in Newham, London.

Aims: To assess the epidemiology of dental injuries among schoolchildren in Newham, London.

Material And Methods: This study was carried out as part of the annual Community Dental Service's School Dental Inspection (SDI) programme in Newham. All schoolchildren aged 14 years were invited to participate in the study.

Apolipoprotein E4 and coronary heart disease in middle-aged men who smoke: a prospective study.

Background: The common isoforms of apolipoprotein E (apoE), E2, E3, and E4, are important determinants of plasma lipid concentrations, and the epsilon4 allele is associated with raised risk of coronary heart disease. We investigated whether the effect of smoking on coronary heart disease risk is affected by APOE genotype.

Methods: We enrolled 3052 middle-aged men who were free of coronary heart disease for prospective cardiovascular surveillance in the second Northwick Park Heart Study (NPHSII).

Children's emotional and behavioural well-being and the family environment: findings from the Health Survey for England.

Recent trends towards diversity in family structure have posed important challenges for traditional social theories on the family. This critical debate has not, however, had much influence on policy discussions of the impact of diverse family structures on children's psychological health, where two-parent families are presumed ideal. In 1997, the annual Health Survey for England focussed on the health of children and young people.

A national evaluation of specialists' clinics in primary care settings.

Background: Encouraged by the increased purchasing power of general practitioners (GPs), specialist-run clinics in general practice and community health care settings (known as specialist outreach clinics) have increased rapidly across England. The activities of local commissioning schemes within primary care groups are likely to accelerate this trend.

Aim: To evaluate the costs, processes, and benefits of specialists' outreach clinics held in GPs' surgeries, compared with hospital outpatient clinics.

Hepatocyte Growth Factor/scatter factor-induces phosphorylation of cortactin in A431 cells in a Src kinase-independent manner.

The Hepatocyte Growth Factor receptor transduces proliferating and scattering signals in epithelial and endothelial cells. We have explored potential interactions of the HGF/SF receptor beta-subunit (p145(beta MET)) with F-actin binding partners aiming to identify novel downstream effectors implicated in HGF/SF pluripotent signalling. Cortactin, a p80/85 F-actin binding protein, was found phosphorylated on tyrosine in response to HGF-SF in A431 human epidermoid carcinoma cells, expressing the HGF/SF receptor (c-MET).

Rapid and radical amniodrainage in the treatment of severe twin-twin transfusion syndrome.

We have evaluated the role of a rapid and radical method of amniodrainage in the treatment of severe twin-twin transfusion. The outcome of 15 patients with severe twin-twin transfusion for which a amniodrainage was performed by means of a vacuum bottle system was compared with the outcome of 15 patients with a similar condition, matched for gestational age at the time of the initial procedure and drained using a standard procedure. In the study group the amniodrainage ended when no amniotic fluid could be aspirated, whereas the women in the standard group were drained with a syringe system and the fluid was removed until the deepest amniotic fluid pool was <8 cm.

Genetic association studies of schizophrenia using the 8p21-22 genes: prepronociceptin (PNOC), neuronal nicotinic cholinergic receptor alpha polypeptide 2 (CHRNA2) and arylamine N-acetyltransferase 1 (NAT1).

Schizophrenia is a common, genetically heterogeneous disorder with a lifetime prevalence of approximately 1% in the general population. Linkage studies of affected families have now strongly implicated a susceptibility locus on chromosome 8p21-22. Tests of allelic association with markers on 8p21-22 should be able to localise any quantitative trait nucleotides (QTN's) or susceptibility mutations to within a few hundred kilobases.

Proteomics--post-genomic cartography to understand gene function.

The completion of the genomic sequences of numerous organisms from human and mouse to Caenorhabditis elegans and many microorganisms, and the definition of their genes provides a database to interpret cellular protein-expression patterns and relate them to protein function. Proteomics technologies that are dependent on mass spectrometry and involve two-dimensional gel electrophoresis are providing the main window into the world of differential protein-expression analysis. In this article, the limitations and expectations of this research field are examined and the future of the analytical needs of proteomics is explored.

Oestriol and oestradiol increase cell to cell communication and connexin43 protein expression in human myometrium.

Oestradiol increases the protein expression of connexin43 (Cx43) gap junctions in myometrium but the effect of oestriol on gap junction expression has not been described previously. Oestriol is the most abundant free oestrogen in pregnant women and there is a marked surge in oestriol concentrations before term and idiopathic preterm labour. In order to determine whether oestriol may have a physiological action on the myometrium, cultured human myometrial cells obtained from non-pregnant hysterectomy specimens were exposed to 10 nmol/l oestradiol or oestriol.

M. tuberculosis: immunology and vaccination.

Tuberculosis is increasing. Current treatment regimens require at least 6 months, because latent or stationary phase organisms are difficult to kill. Such regimens do not achieve full compliance, and "directly observed therapy short course" (DOTS) is having less impact than expected.

The association of heart-rate variability with cardiovascular risk factors and coronary artery calcification: a study in type 1 diabetic patients and the general population.

Objective: To examine the association of heart-rate variability with cardiovascular risk factors and coronary calcification in type 1 diabetic and nondiabetic subjects without a history of cardiovascular disease. Reduced heart-rate variability is associated with increased risk of coronary events. Whether it is associated with coronary atherosclerosis is unknown.

Tuberculosis in disadvantaged groups.

Tuberculosis remains predominantly a disease of the disadvantaged and marginalized. The incidence of the disease is increasing in many industrially developed countries, particularly among the poor, ethnic minorities, prisoners and other institutionalized persons, and the socially isolated and hard to reach groups. Strengthening of the tuberculosis services is required to care for these groups.