Characterization of IgG autoantibodies to extracellular matrix protein 1 in lichen sclerosus.

Although the precise aetiology of lichen sclerosus is unknown, evidence for an autoimmune basis to the disorder is emerging. Indeed, circulating IgG autoantibodies to the glycoprotein extracellular matrix protein 1 (ECM1) have been demonstrated in the sera of about 75% of affected individuals. To assess this humoral immune response further, immunoblotting was performed using bacterial recombinant proteins spanning different domains of the ECM1 protein.

Information theoretic similarity measures in non-rigid registration.

Mutual Information (MI) and Normalised Mutual Information (NMI) have enjoyed success as image similarity measures in medical image registration. More recently, they have been used for non-rigid registration, most often evaluated empirically as functions of changing registration parameter. In this paper we present expressions derived from intensity histogram representations of these measures, for their change in response to a local perturbation of a deformation field linking two images.

Umbilical cord trace elements and minerals and risk of early childhood wheezing and eczema.

It has been suggested that foetal nutrition might influence the inception of wheezing and atopic disorders in childhood but specific nutrients have not been implicated. In the Avon Longitudinal Study of Parents and Children umbilical cord samples were assayed for trace elements and minerals, and mothers were asked about wheezing and eczema in their children. Associations of cord concentrations of selenium, zinc, copper, manganese, magnesium, iron, lead and mercury with wheezing at 30-42 months, with wheezing patterns defined by the presence or absence of transient infant, later onset or persistent wheezing at 0-6 months and 30-42 months, respectively (n=2,044), and with eczema at 18-30 months (n=2,173), were analysed.

Successful treatment of severe psoriasis and psoriatic arthritis with adalimumab.

Adalimumab, a fully human-derived recombinant monoclonal antibody against tumour necrosis factor-alpha, has been shown to be effective for the treatment of patients with moderately to severely active rheumatoid arthritis. We report two patients with long-standing recalcitrant psoriasis and psoriatic arthritis who, after multiple treatment failures with conventional and experimental antipsoriatic medications, both responded to treatment with adalimumab. Significant clinical improvement was noted in both skin and joint disease in the two patients after several weeks of treatment with adalimumab.

Increased risk of squamous cell carcinoma in junctional epidermolysis bullosa.

Non-Herlitz junctional epidermolysis bullosa (JEB) is an autosomal recessive genodermatosis characterized by skin fragility and blistering. It is usually caused by mutations in the genes encoding the basement membrane proteins laminin 5 or type XVII collagen. Clinically, impaired wound healing and chronic erosions cause major morbidity in affected patients.

Proliferative aspects of airway smooth muscle.

Increased airway smooth muscle (ASM) mass is perhaps the most important component of the airway wall remodeling process in asthma. Known mediators of ASM proliferation in cell culture models fall into 2 categories: those that activate receptors with intrinsic receptor tyrosine kinase activity and those that have their effects through receptors linked to heterotrimeric guanosine triphosphate-binding proteins. The major candidate signaling pathways activated by ASM mitogens are those dependent on extracellular signal-regulated kinase and phosphoinositide 3'-kinase.

Tc2 cells respond to soluble antigen in the respiratory tract and induce lung eosinophilia and bronchial hyperresponsiveness.

The key role of T helper 2 (Th2) cells in asthma is well established. In contrast, the function of CD8+ T cells producing a distinct cytokine profile similar to Th2 cells is largely unknown. To analyze a potential role of CD8+ T cell subsets, allergen-specific, in vitro-differentiated T cytotoxic (Tc1 or Tc2) cells from T cell receptor transgenic OT-I mice were adoptively transferred into naive C57BL/6 mice.

Cytidine deamination of retroviral DNA by diverse APOBEC proteins.

The human cytidine deaminase APOBEC3G edits both nascent human immunodeficiency virus (HIV) and murine leukemia virus (MLV) reverse transcripts, resulting in loss of infectivity. The HIV Vif protein is able to protect both viruses from this innate restriction to infection. Here, we demonstrate that a number of other APOBEC family members from both humans and rodents can mediate anti-HIV effects, through cytidine deamination.

What constructs do GPs use when diagnosing psychological problems?

Background: The mismatch between general practice and psychiatric diagnosis of psychological problems has been frequently reported.

Aims: To identify which items from the 28-item general health questionnaire (GHQ-28) best predicted general practitioners' (GPs') own assessments of morbidity and the proportion of time spent in consultations on psychological problems.

Design Of Study: Cross-sectional survey.

Radiation-induced malignancies following radiotherapy for breast cancer.

With advances in diagnosis and treatment, breast cancer is becoming an increasingly survivable disease resulting in a large population of long-term survivors. Factors affecting the quality of life of such patients include the consequences of breast cancer treatment, which may have involved radiotherapy. In this study, we compare the incidence of second primary cancers in women who received breast radiotherapy with that in those who did not (non-radiotherapy).

Copying referral letters to patients: prepare for change.

The National Health Service (NHS) Plan for England has directed that from April 2004 clinicians will offer patients the opportunity to receive copies of letters that are written about them. Patients like to have more information and patients who have received copies of letters have found them useful. It is hoped that copying letters will improve relationships between doctors and patients, encourage patients to be better informed, and improve the quality of information provided to patients.

APOBEC-mediated editing of viral RNA.

Retroviral DNA can be subjected to cytosine-to-uracil editing through the action of members of the APOBEC family of cytidine deaminases. Here we demonstrate that APOBEC-mediated cytidine deamination of human immunodeficiency virus (HIV) virion RNA can also occur. We speculate that the natural substrates of the APOBEC enzymes may extend to RNA viruses that do not replicate through DNA intermediates.

Evaluating palliative care: bereaved family members' evaluations of patients' pain, anxiety and depression.

Palliative care surveys often rely on bereaved family members to act as proxies to provide information on patient care at the end of life, after the patient's death. However, when comparing bereaved family members' assessments with those of the patients, agreement is found to be better for symptoms that are more concrete and observable than subjective aspects such as psychological symptoms and pain. To date, little is known about how proxies actually evaluate these types of symptoms.

Evaluation of a BP180-NC16a enzyme-linked immunosorbent assay in the initial diagnosis of bullous pemphigoid.

Background: Bullous pemphigoid (BP) is the most common subepidermal immunobullous disease, characterized by circulating IgG autoantibodies targeting BP180 and BP230 hemidesmosomal proteins. Several immunological studies have demonstrated that the membrane proximal noncollagenous domain NC16a of BP180 is the immunodominant region targeted by BP autoantibodies. Recently, a commercial BP180 NC16a-specific enzyme-linked immunosorbent assay (ELISA) has become available for detecting pathogenic anti-BP180 autoantibodies in BP sera.

Calcium, mitochondria and oxygen sensing in the pulmonary circulation.

A key event in hypoxic pulmonary vasoconstriction (HPV) is the elevation in smooth muscle intracellular Ca2+ concentration. However, there is controversy concerning the source of this Ca2+, the signal transduction pathways involved, and the identity of the oxygen sensor. Although there is wide support for the hypothesis that hypoxia elicits depolarisation via inhibition of K+ channels, and thus promotes Ca2+ entry through L-type channels, a significant number of studies are inconsistent with this mechanism being either the sole or even major means by which Ca2+ is elevated during HPV.

A randomised controlled trial of a psycho-educational intervention to aid recovery in infectious mononucleosis.

Objectives: Glandular fever is associated with an approximate fivefold increase in fatigue at 6 months. Reduced levels of fitness and illness beliefs may be important predictors of fatigue following glandular fever. We therefore developed a brief psycho-educational intervention aimed at improving recovery from infectious mononucleosis, and piloted a randomised controlled trial to evaluate the intervention.

Stress cytokines: pivotal proteins in immune regulatory networks; Opinion.

Stress proteins have three immunological regulatory functions: within the cell, on the cell membrane as signalling receptors, and in the extracellular environment as stress cytokines. They can activate the immune system by providing danger signals or they may downregulate immune and inflammatory responses. In addition, they can modulate immune responses by acting as chaperones for antigenic peptides while they themselves are processed and presented to T cells as self-peptides.

Protecting and using patient information: the role of the Caldicott Guardian.

All patient information is confidential and must be protected and used appropriately by all members of the healthcare team. Caldicott Guardians have a strategic, advisory and facilitative role to ensure that the Caldicott Principles underpin the approach organizations develop to protect and use patient identifiable information. It is essential all staff and students receive appropriate training and are aware that the responsibility for protecting and using patient information lies with the organisation headed by the Chief Executive and with each individual.

One liver, three recipients: segment IV from split-liver procedures as a source of hepatocytes for cell transplantation.

Hepatocyte transplantation is emerging as a possible treatment for patients with acute liver failure and liver-based metabolic disorders. With the limited availability of donor tissue, it is important to find new sources of liver tissue for isolation of high-quality hepatocytes. Segment IV with or without the caudate lobe was removed during three split-liver procedures.

HLA-DQ-regulated T-cell responses to islet cell autoantigens insulin and GAD65.

HLA-DQ is strongly associated with genetic predisposition to type 1 diabetes. It is assumed that HLA-DQ molecules exert their effects on the disease via the presentation of peptides from islet autoantigens to CD4(+) T-cells, but little information regarding HLA-DQ-restricted, islet antigen-specific, autoreactive T-cells is available. To investigate the role of HLA-DQ in the immune response to islet autoantigens, we measured T-cell proliferation to insulin and GAD65 in the presence and absence of monoclonal antibodies that block HLA-DQ-mediated antigen presentation in recent-onset type 1 diabetic patients and their siblings.

Exhaled nitric oxide levels in infants with chronic lung disease.

Unlabelled: Chronic lung disease (CLD) is an inflammatory disorder; in patients with other inflammatory disorders exhaled nitric oxide (NO) levels are elevated. The aim of this study was to test the hypothesis that prematurely born infants with CLD would have elevated exhaled NO levels compared to those without CLD and healthy term-born infants. Ten infants with CLD (median gestational age 26 weeks; CLD group), ten infants without CLD (median gestational age 32 weeks; non-CLD group) and ten term-born infants (term group) were examined at post-conceptional ages between 36 and 45 weeks.

Impact of educational preparation on medical students in transition from final year to PRHO year: a qualitative evaluation of final-year training following the introduction of a new year 5 curriculum in a London medical school.

This study is a qualitative evaluation of PRHOs' perceptions of a new final year of the MB BS programme at Guy's, King's and St Thomas' (GKT) School of Medicine, undertaken in 2001 as a precursor to a prospective study. One-to-one interviews were carried out with 16 PRHOs two to four months after starting. These were independently thematically analysed, cross-referenced and joint agreement on the themes reached.

A controlled investigation of the cause of chronic idiopathic axonal polyneuropathy.

To investigate the aetiology of chronic idiopathic axonal polyneuropathy (CIAP), 50 consecutive patients were compared with 50 control subjects from the same region. There were 22 patients with painful neuropathy and 28 without pain, 26 with sensory neuropathy and 24 with sensory and motor neuropathy. The typical picture was a gradually progressive sensory or sensory and motor neuropathy.

Oral tolerization with peptide 336-351 linked to cholera toxin B subunit in preventing relapses of uveitis in Behcet's disease.

Behcet's disease (BD) specific peptide (p336-351) was identified within the human 60 kD heat shock protein (HSP60). Oral p336-351 induced uveitis in rats which was prevented by oral tolerization with the peptide linked to recombinant cholera toxin B subunit (CTB). This strategy was adopted in a phase I/II clinical trial by oral administration of p336-351-CTB, 3 times weekly, followed by gradual withdrawal of all immunosuppressive drugs used to control the disease in 8 patients with BD.

Ethnic differences in risk factors for ischemic stroke: a European case-control study.

Background And Purpose: The aim is to estimate the relative risk and population attributable risk (PAR) of risk factors for ischemic stroke by ethnic group.

Methods: In this case-control study, cases of first ischemic stroke were taken from the South London Stroke Register and controls from a cross-sectional prevalence survey covering the same area. PAR was determined for each risk factor by ethnic group.