The effect of APOA5 and APOC3 variants on lipid parameters in European Whites, Indian Asians and Afro-Caribbeans with type 2 diabetes.

Common variants in APOA5 and APOC3 have been associated with differences in plasma triglyceride (TG) levels in healthy individuals. The aim of this study was to examine the association of APOA5 (-1131T>C, S19W) and APOC3 (-482C>T, 1100C>T) polymorphisms in patients with type 2 diabetes (T2D) of European White (EW) (n=931), Indian Asian (IA) (n=610) and Afro-Caribbean (AC) (n=167) origin, with lipid and T2D parameters. Rare allele frequencies and linkage disequilibrium differed significantly amongst ethnic groups.

Lipoprotein-associated phospholipase A2 A379V variant is associated with body composition changes in response to exercise training.

Lipoprotein-associated PLA2 (Lp-PLA2) hydrolyses the sn-2 position of glycerophospholipids, in particular platelet activating factor (PAF), generating significant amounts of Lyso-PAF which in turn, via a remodelling pathway, can generate arachidonic acid (AA) from alkyl-acyl-glycerophosphorylcholine. AA is a precursor for prostaglandin synthesis, which regulates adipogenesis through the peroxisome proliferator-activated receptor subfamily. AA may also modulate skeletal muscle growth.

Radiofrequency ablation (RFA) as a cytoreductive strategy for hepatic metastasis from breast cancer.

Introduction: Patients with liver metastasis from breast cancer have a poor prognosis, although this may be improved by hepatectomy in a selected group with disease confined to the liver. We evaluate the effectiveness of radiofrequency ablation (RFA) as a cytoreductive strategy in the management of liver metastasis from primary breast cancer.

Patients And Methods: Nineteen patients with hepatic metastasis from primary breast cancer underwent RFA of their liver lesions between April 1998 and August 2004.

A life course perspective on telomere length and social inequalities in aging.

Longitudinal studies will be needed to test the idea that social class in adult life, or in childhood, influences the rate of change in telomere length in peripheral blood samples.

Outcome of 609 adults after relapse of acute lymphoblastic leukemia (ALL); an MRC UKALL12/ECOG 2993 study.

Most adults with acute lymphoblastic leukemia (ALL) who achieve complete remission (CR) will relapse. We examined the outcome of 609 adults with recurring ALL, all of whom were previously treated on the Medical Research Council (MRC) UKALL12/ECOG2993 study, where the overall survival (OS) of newly diagnosed patients is 38% (95% confidence interval [CI]=36%-41%) at 5 years. By contrast, OS at 5 years after relapse was 7% (95% CI=4%-9%).

Peripheral blood stem cell yield in 400 normal donors mobilised with granulocyte colony-stimulating factor (G-CSF): impact of age, sex, donor weight and type of G-CSF used.

Mobilised peripheral blood is now the main source of stem cells collected from normal donors. We report our experience of mobilising and collecting 400 normal healthy donors using standardised procedures and techniques. Target recipient doses were reached with one aphaeresis in 63% of donors and with two aphereses in 81% of donors.

Allogeneic stem cell transplantation as treatment for myelofibrosis.

Idiopathic myelofibrosis (IMF) is a clonal disorder resulting from the proliferation of aberrant hematopoietic stem cells. Conventional treatment is unsatisfactory, and with the exception of supportive blood transfusions, none of the standard therapies have been shown to confer a survival advantage. Allogeneic stem cell transplantation represents the only treatment modality with proven curative potential.

Gö6976 is a potent inhibitor of the JAK 2 and FLT3 tyrosine kinases with significant activity in primary acute myeloid leukaemia cells.

Aberrant activation of Janus kinase/signal transducers and activators of transcription (JAK/STAT) signalling is implicated in a number of haematological malignancies and effective JAK inhibitors may be therapeutically useful. We found that Gö6976, an indolocarbazole inhibitor of the calcium-dependent isozymes of protein kinase C (PKC), inhibited interleukin 3/granulocyte-macrophage colony-stimulating factor-induced signalling, proliferation and survival whereas Gö6983, a broad spectrum PKC inhibitor, had no such effects. Gö6976 was found to be a direct and potent inhibitor of JAK2 in vitro.

A common variant in the ACE gene is associated with peripheral neuropathy in women with type 2 diabetes mellitus.

Aims: The D allele of the ACE I/D gene variant is associated with higher tissue and serum ACE activity. Previously, studies have suggested an association between the D allele with the microvascular complications of diabetes. The aim of this study was to explore the impact of this genotype in relation to clinically manifest peripheral neuropathy (PN) in a cohort of subjects with type 2 diabetes mellitus (type 2 DM).

Common variants of apolipoprotein A-IV differ in their ability to inhibit low density lipoprotein oxidation.

Apolipoprotein A-IV (apoA-IV) inhibits lipid peroxidation, thus demonstrating potential anti-atherogenic properties. The aim of this study was to investigate how the inhibition of low density lipoprotein (LDL) oxidation was influenced by common apoA-IV isoforms. Recombinant wild type apoA-IV (100 microg/ml) significantly inhibited the oxidation of LDL (50 microg protein/ml) by 5 microM CuSO(4) (P<0.

The importance of alcohol misuse, malnutrition and genetic susceptibility on brain growth and plasticity.

The "dyad: alcoholic mother and foetus" is a very complex entity in which several elements such as genes, metabolism, diet, drugs and social habits play a role at different stages in the development of the fetal brain damage. The literature on the effects of alcohol consumption on the developing brain is extensive but very few evidences have been reported regarding the combined neurotoxic effects of poor nutrition and alcohol consumption. The consequences of ethanol intake alone or combined with poor maternal nutrition appear to be severe and life-long.

Developmental origins of midlife grip strength: findings from a birth cohort study.

Background: There is growing evidence that the prenatal environment has long-term effects on adult grip strength, but little is known about the effects of the postnatal environment. We tested whether prepubertal growth, pubertal growth, or the development of motor and cognitive capabilities was associated with midlife muscle strength independently of other determinants of grip strength.

Methods: Handgrip strength and body size were measured in a representative British sample of 1406 men and 1444 women 53 years old with prospective childhood data.

Neutrophil elastase: mediator of extracellular matrix destruction and accumulation.

Of the myriad proteolytic enzymes implicated in the development of lung disease, neutrophil elastase has undoubtedly some of the most versatile effects. Although its key physiologic role is in innate host defense, it can also participate in tissue remodeling and possesses secretagogue actions that are now recognized as important to local inflammatory responses. Although unopposed neutrophil elastase activity has been implicated in the development of emphysema for several decades, only relatively recently has a pathogenetic function been ascribed to this serine proteinase in situations where excessive extracellular matrix deposition occurs.

The development of the spiral ganglion in the human foetus.

The development of the spiral ganglion was studied in steps sections of 81 human temporal bones. By the 8th week, the spiral ganglion has already separated from the vestibular ganglion. At 13 weeks two distinct populations are observed that correspond to neuron and Schwann cells.

Developmental origins of midlife physical performance: evidence from a British birth cohort.

The authors hypothesized that 1) physical growth, as a marker of the early development of muscle fibers, and 2) advanced childhood motor and cognitive abilities, as markers of central nervous system development, would be positively related to midlife standing balance and chair rising, independently of later life experiences. They tested these hypotheses in a representative British sample of 1,374 men and 1,410 women aged 53 years in 1999 with prospective childhood measures of heights and weights, age at first standing and walking, cognitive ability, and motor coordination. Weight gain before age 7 years was positively related to adult performance in men but not women, independently of later body size, social class, physical activity, and health status.

Evidence-based guidelines for the investigation and medical treatment of recurrent miscarriage.

Recurrent miscarriage (RM; > or =3 consecutive early pregnancy losses) affects around 1% of fertile couples. Parental chromosomal anomalies, maternal thrombophilic disorders and structural uterine anomalies have been directly associated with recurrent miscarriage; however, in the vast majority of cases the pathophysiology remains unknown. We have updated the ESHRE Special Interest Group for Early Pregnancy (SIGEP) protocol for the investigation and medical management of RM.

Placental-related diseases of pregnancy: Involvement of oxidative stress and implications in human evolution.

Miscarriage and pre-eclampsia are the most common disorders of human pregnancy. Both are placental-related and exceptional in other mammalian species. Ultrasound imaging has enabled events during early pregnancy to be visualized in vivo for the first time.

Variation in the UCP2-UCP3 gene cluster predicts the development of type 2 diabetes in healthy middle-aged men.

The impact of the UCP2 -866G>A and UCP3 -55C>T variants on prospective risk of type 2 diabetes was examined over 15 years in 2,936 healthy middle-aged men (mean age 56 years). Conversion to diabetes (n = 169) was associated with higher BMI, blood pressure, cholesterol, triglycerides and C-reactive protein. The hazard ratio (HR) for diabetes of a BMI >30 kg/m(2) was 3.

Soluble vascular cell adhesion molecule-1 and soluble E-selectin are associated with micro- and macrovascular complications in Type 1 diabetic patients.

Objective: There are no large studies in Type 1 diabetic patients that have examined the relation between soluble adhesion molecules and micro- and macrovascular outcomes, although the risks of such complications are high. Therefore, the main objective is to examine the relationship between soluble (s) vascular cell adhesion molecule-1 (sVCAM-1) and sE-selectin and retinopathy, albuminuria, and cardiovascular disease (CVD) in Type 1 diabetic patients.

Methods: Cross-sectional data on 540 Type 1 diabetic patients, with a mean age of 40 years and diabetes duration of 22 years, from the EURODIAB Prospective Complications Study (PCS) were analysed.

High risk of cardiovascular disease in patients with type 1 diabetes in the U.K.: a cohort study using the general practice research database.

Objective: To estimate the absolute and relative risk of cardiovascular disease (CVD) in patients with type 1 diabetes in the U.K.

Research Design And Methods: Subjects with type 1 diabetes (n = 7,479) and five age- and sex-matched subjects without diabetes (n = 38,116) and free of CVD at baseline were selected from the General Practice Research Database (GPRD), a large primary care database representative of the U.

Time and place: putting individual health into context. A multilevel analysis of the British household panel survey, 1991-2001.

Examination of the extent to which time and place affect people's health has been constrained by the resources available to answer this question. A British longitudinal, nationally representative survey of 8301 adults aged 16 years and older living in private households was used to consider the influence of household membership, area of residence and time using multilevel logistic regression. Self-rated health was assessed by general health and limiting illness during periods characterized by economic decline (1992), economic improvement (1996) and prosperity (2000).

Illicit and traditional drug use among ethnic minority adolescents in East London.

Objectives: To explore ethnic variations in the use of illicit and traditional drugs, and the association of indicators of acculturation with drug use among an ethnically diverse representative sample of early adolescents in East London.

Study Design: A cross-sectional questionnaire survey.

Methods: Confidential questionnaires were used to assess 2789 male and female pupils in years 7 and 9, aged 11-14 years old, from a representative sample of 28 secondary schools in East London.

Bactericidal and anti-adhesive properties of culinary and medicinal plants against Helicobacter pylori.

Aim: To investigate the bactericidal and anti-adhesive properties of 25 plants against Helicobacter pylori (H. pylori).

Methods: Twenty-five plants were boiled in water to produce aqueous extracts that simulate the effect of cooking.