Biochemical analyses of the AF10 protein: the extended LAP/PHD-finger mediates oligomerisation.

Leukaemogenesis correlates with alterations in chromatin structure brought about by the gain or loss of interactive domains from regulatory factors that are disrupted by chromosomal translocations. The gene MLL, a target of such translocation events, forms chimaeric fusion products with a variety of partner genes. While MLL appears to be involved in chromatin-mediated gene regulation, the functions of its partner genes are largely speculative.

'Now please wash your hands': the handwashing behaviour of final MBBS candidates.

The Handwashing Liaison Group has pointed out that "The failure of healthcare workers to decontaminate their hands reflects fundamentals of attitudes, beliefs and behaviours". Doctors are known to be poor at handwashing. This poor compliance may have its roots in a failure to learn this behaviour at medical college, where the influence of consultants and other role models may be critical.

Fetal programming of hepatic lobular architecture in the rat demonstrated ex vivo with magnetic resonance imaging.

We demonstrate that MRI imaging at sub-millimetre resolution can distinguish between periportal and perivenous zones of the rat liver lobule. This made it possible to measure the hepatic lobular radius in ex-vivo perfused fixed livers using MRI. Comparisons of histomorphometric and MRI measurements of lobular radius were in good agreement, although MRI measurements were significantly smaller (P< 0.

Biodistribution and bioactivity of tetra-pegylated meta-tetra(hydroxyphenyl)chlorin compared to native meta-tetra(hydroxyphenyl)chlorin in a rat liver tumor model.

It has been proposed that the construction of a photosensitizer-polymer conjugate would lead to an increased selective retention of the drug in tumor tissue resulting in an enhancement of selective tumor destruction by light in photodynamic therapy. In this study the kinetics of a tetra-pegylated derivative of meta-tetra(hydroxyphenyl)chlorin (mTHPC-PEG) were compared with those of native meta-tetra(hydroxyphenyl)chlorin (mTHPC) in a rat liver tumor model. In addition, the time course of bioactivity of both drugs was studied in normal liver tissue.

Identification of a novel mutation R42P in the gap junction protein beta-3 associated with autosomal dominant erythrokeratoderma variabilis.

We report a missense mutation in the gap junction protein beta-3 (encoding Connexin 31), which was detected in only the affected members of a family in which the autosomal dominant skin disease erythrokeratoderma variabilis was segregating. The nucleotide change results in an arginine to proline substitution in codon 42. This residue is positioned on the first transmembrane/first extracellular domain of the gap junction protein with the mutation replacing a negatively charged residue with a nonpolar residue.

Fine genetic mapping of diffuse non-epidermolytic palmoplantar keratoderma to chromosome 12q11-q13: exclusion of the mapped type II keratins.

Diffuse non-epidermolytic palmoplantar keratoderma (NEPPK) belongs to the heterogeneous group of skin diseases characterized by thickening of the stratum corneum of the palms and soles (1). This autosomal dominant PPK is characterized by a diffuse pattern of palmar and plantar hyperkeratosis giving the affected areas a thickened yellowish appearance with a marked erythematous edge. Linkage of diffuse NEPPK to chromosome 12q11-q13 has been demonstrated in two independent reports (2, 3).

Caring for people with HIV in Zambia: are traditional healers and formal health workers willing to work together?

This study of traditional healers and formal health workers determined their knowledge and practices in the field of HIV/AIDS and examined their training needs and attitudes to collaboration, in preparation for planning joint training workshops. Several misconceptions concerning symptoms and transmission of HIV disease were found in both groups, particularly among traditional healers. Twenty healers (51%) and four formal health workers (15%) claimed a cure existed for AIDS.

Zonation of gluconeogenesis, ketogenesis and intracellular pH in livers from normal and diabetic ketoacidotic rats: evidence for intralobular redistribution of metabolic events in ketoacidosis.

The intralobular distribution of metabolism was examined in the livers from rats with severe diabetic ketoacidosis (DKA), perfused at pH 6.8, and compared with that in livers from normal starved animals perfused at either pH 7.4 or 6.

Patient case studies.

Three contrasting cases of obese patients with type 2 diabetes mellitus are presented, which illustrate the management difficulties faced by clinicians. The first raises the issue of when to commence an oral hypoglycaemic agent in a newly diagnosed but asymptomatic obese patient; the second case addresses the problem of when to commence insulin in the face of continuing weight gain and poor glycaemic control; the final case is an example of the vicious metabolic spiral which so many patients enter, with increasing body weight, poor diabetic control and associated co-morbidities. The discussion that follows each case presentation recognises the considerable cardiovascular risk faced by such patients and provides guidance about possible management pathways including adjunctive anti-obesity pharmacotherapy.

The influence of plasma on basal and ACTH-stimulated in vitro adrenocortical steroidogenesis.

Early descriptions of in vitro ACTH bioassays all emphasised the need to use extracted plasma samples due to interference by an unidentified component. The aim of these studies was to elucidate the effects of whole plasma on ACTH steroidogenic activity in vitro and to identify the responsible factor. A sensitive in vitro dispersed bovine adrenocortical cell bioassay was established.

A double blind, randomised, controlled trial of glutamine supplementation in parenteral nutrition.

Background And Aims: To determine whether the inclusion of 20 g free glutamine as part of the nitrogen source of parenteral feeds reduces length of hospital stay or mortality.

Methods: In a randomised, double blind, controlled trial in 168 patients clinically accepted for parenteral nutrition, standard feeds were compared with feeds in which 3.8 g of the total nitrogen was replaced with the equivalent 20 g glutamine.

Effect of postal prompts to patients and general practitioners on the quality of primary care after a coronary event (POST): randomised controlled trial.

Objectives: To determine whether postal prompts to patients who have survived an acute coronary event and to their general practitioners improve secondary prevention of coronary heart disease.

Design: Randomised controlled trial.

Setting: 52 general practices in east London, 44 of which had received facilitation of local guidelines for coronary heart disease.

The management of residual masses after chemotherapy in metastatic seminoma.

Objective: To review our experience in management of residual masses after chemotherapy for metastatic seminoma.

Patients And Methods: The study comprised a review of 107 patients with metastatic seminoma, treated with initial chemotherapy from 1978 to 1996. Forty-three patients had residual masses detected by computed tomography after chemotherapy, while 64 achieved a complete response.

The palmoplantar keratodermas: much more than palms and soles.

The inherited palmoplantar keratodermas (PPKs) are a diverse and often clinically confusing branch of the genetic skin diseases. As the name suggests, the lesions of PPK primarily affect the palms and soles of the feet, although a number of the PPKs are also associated with a genetic predisposition to other conditions, including cancer, hearing loss and heart failure. The mapping and identification of genes that underlie the PPKs reveal new insights into the biological interactions of the structural components of the palmoplantar epidermis and further our understanding of epidermal disease.

Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes.

Autosomal dominant periodic fever syndromes are characterized by unexplained episodes of fever and severe localized inflammation. In seven affected families, we found six different missense mutations of the 55 kDa tumor necrosis factor receptor (TNFR1), five of which disrupt conserved extracellular disulfide bonds. Soluble plasma TNFR1 levels in patients were approximately half normal.

Investigation of under-ascertainment in epidemiological studies based in general practice.

Background: One of the aims of the Study of Infectious Intestinal Disease (IID) in England is to estimate the incidence of IID presenting to general practice. This sub-study aims to estimate and correct the degree of under-ascertainment in the national study.

Methods: Cases of presumed IID which presented to general practice in the national study had been ascertained by their GP.

Basal cell carcinoma development is associated with induction of the expression of the transcription factor Gli-1.

Recent work has established that activation of Hedgehog/patched signalling plays a key role in the development of basal cell carcinomas (BCCs). In Drosophila the effects of hedgehog signalling are mediated by the transcription factor Cubitus interruptus, which is homologous to the mammalian Gli family of transcription factors. In order to investigate the downstream consequences of patched gene inactivation in BCCs, we have investigated the expression of Gli-1 and Gli-3 in normal skin and BCCs by reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization.

Expression pattern and cellular distribution of the murine homologue of AF10.

We have cloned Af10, the murine homologue of the MLL partner gene AF10. The predicted open reading frame of Af10 contains 1069 aa which are 90% identical to those of AF10. Af10 contains an N-terminal cysteine-rich region with a LAP/PHD finger, a leucine zipper domain and a glutamine-rich region at the C-terminus, features also found in the human proteins AF10 and AF17.

Molecular biology of varicella-zoster virus. A review prepared for the UK Advisory Group on Chickenpox.

Varicella-zoster virus (human herpesvirus 3; VZV) is one of eight herpes viruses that routinely infect humans. It is classified as a member of the genus Varicellovirus, subfamily Alphaherpesvirinae, family Herpesviridae. Of the other human herpes viruses it is most closely related to the herpes simplex viruses (also members of the Alphalerpesvirinae).

Electrophoretic DNA analysis for the detection of apoptosis.

There are many techniques available for the detection of apoptotic cells; some are based on morphological changes, others on biochemical events. However, electrophoretic detection of the systematic cleavage of DNA into oligonucleosomal multimers of 180-200 bp remains the "hallmark" of apoptosis. Conventional constant field agarose gel electrophoresis of DNA from apoptotic cells can be used to resolve the multimers into the characteristic DNA ladders indicative of apoptotic cell death.

Linkage of familial Hibernian fever to chromosome 12p13.

Autosomal dominant periodic fevers are characterized by intermittent febrile attacks of unknown etiology and by recurrent abdominal pains. The biochemical and molecular bases of all autosomal dominant periodic fevers are unknown, and only familial Hibernian fever (FHF) has been described as a distinct clinical entity. FHF has been reported in three families-the original Irish-Scottish family and two Irish families with similar clinical features.

Inadequate vitamin D status: does it contribute to the disorders comprising syndrome 'X'?

Environmental factors are important in the aetiology of glucose intolerance, type II diabetes and IHD. The lack of vitamin D, which is necessary for adequate insulin secretion, relates demographically to increased risk of myocardial infarction. These disorders are connected, degenerative vascular disease increasing with glucose intolerance and diabetes and, with its risk factors, comprising syndrome 'X'.