Targeting cytotoxic T lymphocytes for cancer immunotherapy.

In light of their preeminent role in cellular immunity, there is considerable interest in targeting of cytotoxic T-lymphocytes to cancer. This review summarises the active and passive immunotherapeutic approaches under development to achieve this goal, emphasising how recent advances in tumour immunology and gene transfer have impacted upon this field.

No evidence for links between autism, MMR and measles virus.

Background: We examined whether, in the UK, there is an increased risk of autism (AD) following exposures, in early life, to: (1) wild measles; (2) live attenuated measles, alone or in combination as MMR; and (3) the alteration of the mumps strain within MMR.

Method: We conducted time trend analyses of 2407 AD subjects born between 1959-93; and for comparison, 4640 Down's syndrome (DS) subjects born between 1966-93. Between 1968-86, we correlated variations in AD and DS births with wild measles incidence.

Training carers of stroke patients: randomised controlled trial.

Background: Informal care givers support disabled stroke patients at home but receive little training for the caregiving role.

Objective: To evaluate the effectiveness of training care givers in reducing burden of stroke in patients and their care givers.

Design: A single, blind, randomised controlled trial.

Direct interaction of FANCD2 with BRCA2 in DNA damage response pathways.

Fanconi anaemia (FA) is a chromosomal instability disorder characterized by cellular sensitivity to DNA interstrand crosslinking agents and a high risk of cancer. Six of the eight proteins encoded by the known FA genes form a nuclear complex which is required for the monoubiquitination of the FANCD2 protein. FANCD2 complexes and colocalizes with BRCA1, but its presumptive role in DNA repair has not yet been clearly defined.

Serum and salivary IgA antibody responses to Saccharomyces cerevisiae, Candida albicans and Streptococcus mutans in orofacial granulomatosis and Crohn's disease.

Orofacial granulomatosis (OFG) is a condition of unknown aetiology with histological and, in some cases, clinical association with Crohn's disease (CD). However, the exact relationship between OFG and CD remains uncertain. The aim of this study was to determine whether OFG could be distinguished immunologically from CD by comparing non-specific and specific aspects of humoral immunity in serum, whole saliva and parotid saliva in three groups of patients: (a) OFG only (n = 14), (b) those with both oral and gut CD (OFG + CD) (n = 12) and (c) CD without oral involvement (n = 22) and in healthy controls (n = 29).

Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes.

There is increasing evidence that an ongoing cytokine-induced acute-phase response (sometimes called low-grade inflammation, but part of a widespread activation of the innate immune system) is closely involved in the pathogenesis of type 2 diabetes and associated complications such as dyslipidemia and atherosclerosis. Elevated circulating inflammatory markers such as C-reactive protein and interleukin-6 predict the development of type 2 diabetes, and several drugs with anti-inflammatory properties lower both acute-phase reactants and glycemia (aspirin and thiazolidinediones) and possibly decrease the risk of developing type 2 diabetes (statins). Among the risk factors for type 2 diabetes, which are also known to be associated with activated innate immunity, are age, inactivity, certain dietary components, smoking, psychological stress, and low birth weight.

Predicting violence in schizophrenia: a prospective study.

Background: People with schizophrenia are more violent than the general population, but this increased risk is attributable to the actions of a small subgroup. Identifying those at risk has become an essential part of clinical practice.

Aims: To estimate the risk factors for assault in patients with schizophrenia.

Is graded exercise better than cognitive behaviour therapy for fatigue? A UK randomized trial in primary care.

Background: Patients frequently present with unexplained fatigue in primary care, but there have been few treatment trials in this context. We aimed to test cognitive behaviour therapy (CBT) and graded exercise therapy (GET) for patients presenting to their family doctor with fatigue. Secondly, we described the outcome for a cohort of patients who presented to the same doctors with fatigue, who received standard care, plus a booklet.

Gulf war illness--better, worse, or just the same? A cohort study.

Objectives: Firstly, to describe changes in the health of Gulf war veterans studied in a previous occupational cohort study and to compare outcome with comparable non-deployed military personnel. Secondly, to determine whether differences in prevalence between Gulf veterans and controls at follow up can be explained by greater persistence or greater incidence of disorders.

Design: Occupational cohort study in the form of a postal survey.

Non-invasive glucose monitoring by NAD(P)H autofluorescence spectroscopy in fibroblasts and adipocytes: a model for skin glucose sensing.

The aim of this study was to develop an in vitro cell-culture model of skin-component cells to test the hypothesis that glucose can be monitored non-invasively by measuring NAD(P)H-related fluorescence changes in tissues. 3T3-L1 fibroblasts and adipocytes were grown in culture, and the response to added glucose was assessed by changes in steady-state autofluorescence at 400-500 nm [excitation at 340 nm, an index of NAD(P)H]. We also studied glucose-related fluorescence changes in cells stained with the mitochondrial marker, rhodamine-123.

CD4 responses to conserved HIV-1 T helper epitopes show both negative and positive associations with virus load in chronically infected subjects.

Characterization of immune responses to immunodominant CD4 epitopes in HIV-1 that are associated with control of HIV infection could be used to strengthen the efficacy of polyepitope HIV vaccines. We measured both the proliferative and the CD4 interferon (IFN)-gamma and interleukin (IL)-2 cytokine responses specific for 11 previously identified HIV-1 T helper epitopes in 10 HIV-infected non-progressors (LTNPs) (infected for a median of 15 years with a stable CD4 count of >500 cells x 10(6)/l), and seven slow progressors (SPs) (infected for a median of 15 years with a CD4 count that had declined to <500 cells x 10(6)/l). Both groups were antiretroviral treatment-naive at the time of evaluation.

Performance assessment of the Medtronic-MiniMed Continuous Glucose Monitoring System and its use for measurement of glycaemic control in Type 1 diabetic subjects.

Aims: To assess the accuracy, reliability and measurement of glycaemic control associated with the Medtronic-MiniMed Continuous Glucose Monitoring System (CGMS) in comparison with blood glucose self-monitoring (BGSM) in Type 1 diabetic patients.

Methods: Type 1 diabetic patients (n = 18) underwent glucose monitoring by the CGMS for up to 3 days, when control was also assessed by BGSM performed eight times daily.

Results: Ninety-five per cent of paired non calibration samples were in the clinically acceptable zones of the Clarke error grid, and 97% in a consensus grid.

Bi-allelic silencing of the Fanconi anaemia gene FANCF in acute myeloid leukaemia.

Fanconi anaemia (FA) is a chromosomal instability disorder associated with a high risk of acute myeloid leukaemia (AML). Previous work has shown that the AML cell line CHRF-288, derived from a sporadic AML-M7 patient, does not express FANCF protein and exhibits a cellular FA phenotype. We show that this phenotype is corrected by a FANCF-expressing plasmid and that the absence of FANCF protein is explained by hypermethylation of the promoter region of the FANCF gene.

Amino acids for amyotrophic lateral sclerosis / motor neuron disease.

Background: Amyotrophic lateral sclerosis, also known as motor neuron disease, is a progressive neuromuscular disease that causes disability and eventual death. Various amino acid preparations, the three branched-chain amino acids (L-leucine, L-valine and L-isoleucine) or, alternatively, L-threonine have been used as experimental therapy.

Objectives: To examine the efficacy of amino acid therapies in prolonging survival and/or slowing the progression of amyotrophic lateral sclerosis/motor neuron disease.

Distinguishing patients with chronic fatigue from those with chronic fatigue syndrome: a diagnostic study in UK primary care.

Background: Chronic fatigue syndrome (CFS) has been defined, but many more patients consult in primary care with chronic fatigue that does not meet the criteria for CFS. General practitioners (GPs) do not generally use the CFS diagnosis, and have some doubt about the validity of CFS as an illness.

Aim: To describe the proportion of patients consulting their GP for fatigue that met the criteria for CFS, and to describe the social, psychological, and physical differences between patients with CFS and those with non-CFS chronic fatigue in primary care.

Activation of the innate immune system as a predictor of cardiovascular mortality in Type 2 diabetes mellitus.

Aims: Activation of innate immunity may play a major role in the development and pathophysiology of Type 2 diabetes; we therefore investigated whether a marker of innate immunity (serum sialic acid) predicts cardiovascular disease (CVD) and all-cause mortality in Type 2 diabetes.

Methods: Type 2 diabetic subjects (n=128, age 31-64 years at outset) participating in the Lewisham Diabetes Survey were followed up for a mean of 12.8 years.

Location and function of intrahepatic shunts in anaesthetised rats.

Background: In the present study we determined the proportion of shunt flow due to patent intrahepatic portal systemic shunts in the normal rat liver and its relationship with microsphere induced portal hypertension.

Methods: Systemic and hepatic haemodynamics were measured continuously before, during, and after intraportal injection of 15 micro m diameter microspheres in anaesthetised male Wistar rats. Functional hepatic blood flow and intrahepatic shunt flow were determined by the use of constant intraportal infusion of sorbitol and simultaneous measurements in the portal vein, hepatic vein, and carotid artery.