Relationship between carotid atherosclerosis and coronary artery calcification in asymptomatic diabetic patients: A prospective multicenter study.

Background: The value of screening sub-clinical atherosclerosis in asymptomatic patients with type 2 diabetes mellitus (T2DM) remains controversial.

Hypothesis: An integrated model incorporating carotid intima-media thickness (CIMT) and carotid plaque with traditional risk factors can be used to predict prevalence and severity of coronary artery calcification in asymptomatic T2DM patients.

Methods: A cohort of 262 asymptomatic T2DM patients were prospectively studied with carotid ultrasound to evaluate CIMT and carotid plaque and also a computed tomography coronary artery calcium (CT-CAC) scan.

Modern concepts of the natural history of breast cancer: a guide to the design and publication of trials of the treatment of breast cancer.

The design, analysis and interpretation of randomised controlled trials for the management of early breast cancer are to some extent predicated on the prevailing conceptual model of the disease based on its biology and cellular kinetics. Real progress became possible from the early 1970s following the challenge to a mechanistic view of the disease going back to the time of Virchow and Halsted. Improvements in local and systemic therapy that have reduced the surgical morbidity and improved on survival followed the biological revolution lead by Dr.

Determination of cell-specific receptor binding using a combination of immunohistochemistry and in vitro autoradiography: relevance to therapeutic receptor targeting in cancer.

Mapping of receptor binding to specific structures, or cells within tissue samples, provides valuable information regarding biological and pathological mechanisms. Such information may potentially be translated into targeted therapies, especially in the field of cancer treatment. In this chapter, a receptor localization technique is described which utilises frozen sections of human tissue and combines immunohistochemistry (IHC) and micro-autoradiography.

The polymerase chain reaction.

The polymerase chain reaction (PCR) has had a significant impact on all aspects of the molecular biosciences, from cancer research to forensic science. The sensitivity and specificity inherent in the technique allow minute quantities of genetic material to be detected while the unique properties of thermostable DNA polymerase ensure that abundant copies are reliably reproduced to levels that can be visualized and/or used for further applications. This chapter describes applications of PCR and PCR-RT to investigate primary cancer and metastatic disease at both the DNA and mRNA expression levels.

HIV infection associated post-traumatic stress disorder and post-traumatic growth--a systematic review.

The phenomenon of post-traumatic stress has been well documented in the literature as a lasting mental health condition associated with exposure to traumatic life events. The diagnosis and experience of human immunodeficiency virus (HIV) disease may be such a trauma. On the other hand, the phenomenon of post-traumatic growth (PTG) has been described, whereby people show positive mental health growth in the face of such trauma.

ANGPTL4 variants E40K and T266M are associated with lower fasting triglyceride levels in Non-Hispanic White Americans from the Look AHEAD Clinical Trial.

Background: Elevated triglyceride levels are a risk factor for cardiovascular disease. Angiopoietin-like protein 4 (Angptl4) is a metabolic factor that raises plasma triglyceride levels by inhibiting lipoprotein lipase (LPL). In non-diabetic individuals, the ANGPTL4 coding variant E40K has been associated with lower plasma triglyceride levels while the T266M variant has been associated with more modest effects on triglyceride metabolism.

Genetic variation within IL18 is associated with insulin levels, insulin resistance and postprandial measures.

Background And Aims: IL-18 expression is up-regulated in atherosclerotic plaques, and higher levels are seen in obese and Type 2 Diabetic individuals. More recently, a possible role for IL-18 in glucose and energy homeostasis has been suggested.

Methods And Results: We investigated variation within the IL18 gene and its association with measures of obesity and the metabolic syndrome.

APOE, CETP and LPL genes show strong association with lipid levels in Greek children.

Background And Aims: Studies have consistently demonstrated that variants in a number of candidate genes are significant determinants of lipid levels in adults. However, few studies have investigated the impact of these variants in children. Therefore, in the present investigation we examined the influence of ten common variants in the genes for lipoprotein lipase (LPL-S447X), cholesterol ester transfer protein (CETP-Taq1B) apolipoprotein (APO) E (epsilon2, epsilon3, epsilon4), APOA5 (-1131C>T and S19W), APOA4 (S347T) and APOC3 (-482C>T; 1100C>T and 3238G>C) on lipoprotein levels children from the Gene-Diet Attica Investigation on childhood obesity (GENDAI).

FISH mapping of Philadelphia negative BCR/ABL1 positive CML.

Background: Chronic myeloid leukaemia (CML) is a haematopoietic stem cell disorder, almost always characterized by the presence of the Philadelphia chromosome (Ph), usually due to t(9;22)(q34;q11) or its variants. The Ph results in the formation of the BCR/ABL1 fusion gene, which is a constitutively activated tyrosine kinase. Around 1% of CML patients appear to have a Ph negative karyotype but carry a cryptic BCR/ABL1 fusion that can be located by fluorescence in situ hybridisation (FISH) at chromosome 22q11, 9q34 or a third chromosome.

What is the clinical utility of DNA testing in patients with familial hypercholesterolaemia?

Purpose Of Review: Familial hypercholesterolaemia is a common genetic disorder of lipid metabolism in which patients have a significantly elevated risk of early coronary heart disease, which can be substantially lowered by treatment with the statin class of drugs. In many countries in Europe, tracing of relatives using DNA information, once the family mutation has been identified, is being actively carried out. The present review examines the specificity and clinical utility of DNA testing in patients with familial hypercholesterolaemia.

Cardiovascular disease risk prediction using genetic information (gene scores): is it really informative?

Purpose Of Review: DNA-based tests for assessment of genetic predisposition to coronary heart disease need to provide information over and above that of conventional risk factors. The efficacy of selected 'candidate' gene loci in risk algorithms, to improve the predictive accuracy for coronary heart disease, remains to be demonstrated.

Recent Findings: Although many candidate genes for coronary heart disease have been tested, the optimal set of risk genotypes has yet to be identified.

Diabetes: managing dyslipidaemia.

Introduction: Dyslipidaemia is a major contributor to the increased risk of heart disease found in people with diabetes. An increase of 1 mmol/L LDL-C is associated with a 1.57-fold increase in the risk of coronary heart disease (CHD) in people with type 2 diabetes.

Genomic profile of chronic myelogenous leukemia: Imbalances associated with disease progression.

The expression of the chimeric BCR/ABL1 fusion gene resulting from t(9;22)(q34;q11) in chronic myelogenous leukemia (CML) is necessary for malignant transformation, but not sufficient to maintain disease progression. The appearance of various chromosomal and molecular alterations in the accelerated and terminal phase of CML is well documented, but evidence for causal relationship is largely lacking. We carried out a genome wide screening at a resolution of 1 Mb of 54 samples at different stages of CML together with 12 CML cell lines and found that disease progression is accompanied by a spectrum of recurrent genome imbalances.

Is the influence of variation in the ACE gene on the prospective risk of Type 2 diabetes in middle-aged men modified by obesity?

There is strong evidence for the presence of a functional renin-angiotensin system in diabetogenic tissues, and ACE (angiotensin-converting enzyme) inhibitors may improve glucose metabolism in those individuals at high risk of developing T2DM (Type 2 diabetes). In the present study, we tested the hypothesis that subjects with genetically lower plasma and tissue ACE activity, because of their ACE [I/D (insertion/deletion)] genotype, would have a lower risk of T2DM in 2642 healthy middle-aged Caucasian men (mean age, 56 years) followed-up for 15 years. Obesity was the strongest predictor of T2DM, with an HR (95% CI) [hazard ratio (95% confidence interval)] of 3.

Angiotensin-converting enzyme genotype interacts with systolic blood pressure to determine coronary heart disease risk in healthy middle-aged men.

The impact of the ACE I/D polymorphism on coronary heart disease (CHD) risk is modest at most, however it may act as a modifier gene. ACE genotype was determined in 2711 healthy middle-aged men (mean age 56 years) followed for 15 years. No genotype-CHD risk association was found, but when analyzed by quartiles of systolic blood pressure (SBP), compared with II homozygotes, carriage of each additional D allele was protective at lower SBP, but in the highest quartile (SBP >150 mm Hg) conferred almost 1.

Is the promotion of physical activity in vulnerable older people feasible and effective in general practice?

There is convincing evidence about the benefits of exercise training in community dwelling frailer older people, but little evidence that this intervention can be delivered in general practice. In this prospective cohort study in 14 general practices in north London we assessed the feasibility and effectiveness of a tailored exercise referral programme for frail elderly patients delivered within a variety of inner city primary care settings. One hundred and twenty-six women and 32 men aged 75 years and older, deemed borderline frail by their GPs, took part in a two-phase progressive exercise programme (Stage 1--primary care setting; Stage II--leisure/community centre setting) using the Timed Up And Go (TUG) test as the primary outcome measure.

Expression of a novel cytokine, IL-4delta2, in HIV and HIV-tuberculosis co-infection.

Background: Correcting the Th2 shift in HIV/AIDS represents a potential intervention strategy. However data on interleukin (IL)-4 expression in HIV or AIDS are un-interpretable because of failure to distinguish between IL-4 and its splice variant and natural antagonist, IL-4delta2.

Objective: To determine Th1 [interferon (IFN)-gamma], IL-4delta2 and Th2 (IL-4) expression in whole blood and lung lavage from healthy volunteers and in HIV or HIV-tuberculosis (TB) co-infection.

Recruiting patients to medical research: double blind randomised trial of "opt-in" versus "opt-out" strategies.

Objective: To evaluate the effect of opt-in compared with opt-out recruitment strategies on response rate and selection bias.

Design: Double blind randomised controlled trial.

Setting: Two general practices in England.

A prospective randomized trial of N-acetyl cysteine administration during cold preservation of the donor liver for transplantation.

Aims: N-acetyl cysteine (NAC), an anti oxidant and a glutathione precursor, is effective in ameliorating liver injury of Tylenol overdose. There is experimental evidence that it also reduces ischemia reperfusion (I/R) injury. This clinical study was undertaken to study the effect of NAC administered in the donor operation.

Development, characterisation and epitope mapping of novel monoclonal antibodies for DJ-1 (PARK7) protein.

Mutations in DJ-1 (PARK7) were recently identified as the cause for an autosomal recessive early onset form of familial Parkinson's disease, however, the function of the protein in the brain is yet to be elucidated. Here we report on the development, characterisation and epitope mapping, of two novel monoclonal antibodies to DJ-1. One of them (DJ-1 "clone16") has its epitope between amino acids 56-78 of the human DJ-1 protein and has very similar properties to a commercially available DJ-1 antibody clone 3E8.

Synphilin-1 and parkin show overlapping expression patterns in human brain and form aggresomes in response to proteasomal inhibition.

Lewy bodies (LBs) are the characteristic inclusions of Parkinson's disease brain but the mechanism responsible for their formation is obscure. Lewy bodies (LBs) are composed of a number of proteins of which alpha-synuclein (alpha-SYN) is a major constituent. In this study, we have investigated the distribution patterns of synphilin-1 and parkin proteins in control and sporadic PD brain tissue by immunohistochemistry (IH), immunoblotting, and immunoelectron microscopy (IEM).