Steroid sulphatase: expression, isolation and inhibition for active-site identification studies.

Steroid sulphatase, which can hydrolyse 3-hydroxysteroid sulphates, has important roles in several physiological and pathological processes. A number of steroid sulphatase inhibitors have now been developed, of which the most potent to date is oestrone-3-O-sulphamate (EMATE). This inhibitor inactivates steroid sulphatase in an irreversible, time- and concentration-dependent manner.

Macrophage colony-stimulating factor increases bone resorption by osteoclasts disaggregated from human fetal long bones.

Macrophage colony-stimulating factor (M-CSF) is known to play an important role in human and murine osteoclast formation. Although M-CSF has been shown to inhibit isolated neonatal rat osteoclasts from resorbing bone, its action on the mature human osteoclast has not been described. We now report that M-CSF increases osteoclastic bone resorption in a dose-responsive manner.

Developmentally regulated responses of human granulosa cells to insulin-like growth factors (IGFs): IGF-I and IGF-II action mediated via the type-I IGF receptor.

In experimental animal models, insulin-like growth factors (IGFs) have been found to be more potent stimulators of ovarian function than insulin. In human theca cells, however, insulin, IGF-I, and IGF-II have similar effects on androgen production. The relative effects of insulin and IGFs on human granulosa cell steroidogenesis is unknown.

Correlation between varying levels of PMP22 expression and the degree of demyelination and reduction in nerve conduction velocity in transgenic mice.

Charcot-Marie-Tooth disease type 1A is most commonly caused by a duplication of a 1.5 Mb region of chromosome 17 which includes the peripheral myelin protein 22 gene (PMP22). Over-expression of this gene leads to a hypomyelinating/demyelinating neuropathy and to severely reduced nerve conduction velocity.

Arginase activity is modulated by IL-4 and HOArg in nephritic glomeruli and mesangial cells.

Arginase shares a common substrate, L-arginine, with nitric oxide synthase (NOS). Both enzymes are active at inflammatory sites. To understand regulation of arginase and its relationship to nitric oxide (NO) production, we studied effects of NG-hydroxy-L-arginine (HOArg) and interleukin-4 (IL-4) on urea and NO2- synthesis by glomeruli during rat immune glomerulonephritis and compared these with macrophages and glomerular mesangial cells (MC).

Inhibition of human immunodeficiency virus replication and growth advantage of CD4+ T cells from HIV-infected individuals that express intracellular antibodies against HIV-1 gp120 or Tat.

Current clinical gene therapy protocols for the treatment of human immunodeficiency virus type 1 (HIV-1) infection often involve the ex vivo transduction and expansion of CD4+ T cells derived from HIV-positive patients at a late stage in their disease (CD4 count <400). These protocols involve the transduction of T cells by murine leukemia virus (MLV)-based vectors encoding antiviral constructs such as the rev m10 dominant negative mutant or a ribozyme directed against the CAP site of HIV-1 RNA. We examined the efficiency and stability of transduction of CD4+ T cells derived from HIV-infected patients at different stages in the progression of their disease, from seroconversion to AIDS.

Serotyping of HIV type 1 infections: definition, relationship to viral genetic subtypes, and assay evaluation. UNAIDS Network for HIV-1 Isolation and Characterization.

V3 serotyping refers to a system based on binding of antibody in patient sera to V3-loop peptides derived from HIV-1 env genetic subtypes. The V3x serotype represents reactivity of serum from an HIV-1-infected patient (regardless of viral genetic subtype), which reacts preferentially to a V3 peptide derived from the X subtype sequence. We have classified HIV-1 serotypes, determined the relationship between the HIV-1 V3 serotypes and viral genetic subtypes in a large study (n = 125), and evaluated the performance of three different V3 peptide-binding assays.

Protectionism or competition in managing British nursing research? Current debate among nurse and midwifery teachers.

Aim: The intention is to highlight key issues related to research by nurse and midwifery teachers.

Background: The debate centres on the 'culture change' facing teachers from traditional colleges moving to universities where a more formal research requirement prevails.

Origins Of Information: Data were drawn from selected official reports and other literature informing the introductory discussion.

Heme oxygenase is induced in nephrotoxic nephritis and hemin, a stimulator of heme oxygenase synthesis, ameliorates disease.

Heme oxygenase (HO) catalyses degradation of heme to biliverdin, iron and carbon monoxide (CO). Two isoforms exist, a constitutive form and an inducible form (HO-1). Induction of HO-1 may have protective effects in inflammation.

Interventional MR-guided excisional biopsy of breast lesions.

Interventional MR (IMR) machines have produced unique opportunities for image-guided surgery. The open configuration design and fast pulse sequences allow intraoperative scanning to monitor procedures. This study was undertaken to assess the potential use of IMR for image-guided surgery.

Hypotensive and regional haemodynamic effects of exercise, fasted and after food, in human sympathetic denervation.

1. In human sympathetic denervation due to primary autonomic failure, food and exercise in combination may produce a cumulative blood pressure lowering effect due to simultaneous splanchnic and skeletal muscle dilatation unopposed by corrective cardiovascular reflexes. We studied 12 patients with autonomic failure during and after 9 min of supine exercise, when fasted and after a liquid meal.

Multiple functions within the Epstein-Barr virus EBNA-3A protein.

Two regions of the EBNA-3A protein of Epstein-Barr virus were shown to be capable of binding to the cell protein RBP-Jk (also known as CBF-1), a component of the Notch signaling pathway. Consistent with this binding, EBNA-3A inhibited reporter gene expression from plasmids containing RBP-Jk DNA binding sites within their promoters, including the Cp promoter. When EBNA-3A was linked to a GAL4 DNA binding domain, it repressed the activity of a promoter containing GAL4 binding sites at all plasmid concentrations tested.

Hepatitis G virus does not cause significant liver disease after liver transplantation.

The aim of this study was to determine the prevalence of infection with the newly described hepatitis G virus (HGV) in a liver transplant cohort, and to establish the frequency and nature of hepatitis in those with and without HGV infection. A reverse transcriptase-polymerase chain reaction technique was employed to determine viraemia in the patients, and liver biopsies taken at different times after transplantation were assessed histologically. Hepatitis G virus RNA was detected in 47% of the liver transplant recipients investigated.

Fate of thianthrene in rat.

1. Radiolabelled thianthrene was administered by gavage (200 mg/kg body weight) to the adult female Wistar rat following an overnight fast. 2.

Inhibition of bone resorption by 17beta-estradiol in human bone marrow cultures.

Estrogen deficiency puts individuals at risk of developing osteoporosis because it causes increased bone resorption. However, the mechanism by which this occurs is not known. We have shown, using a recently described two-phase human bone marrow culture system, that estradiol (17beta-E2) added to phase I results in inhibition of bone resorption by reducing the number of osteoclasts (identified as vitronectin receptor and/or calcitonin receptor-positive cells) formed in the cultures.

Vascular smooth muscle cell migration, atherosclerosis, and calcium channel blockers.

Calcium channel blockers have been studied widely for their potential ability to retard or even reverse atherosclerosis. Several potential cellular mechanisms have been proposed, including interactions with vascular smooth muscle cells: migration, inhibition of proliferation, or both. This paper reviews some of the signaling events involved in smooth muscle cell migration, including changes in intracellular calcium, and the inhibition of cell migration by calcium channel blockers.

Calcium antagonists and atherosclerosis.

Calcium channel blockers (CCBs) have several properties which may have beneficial effects on the development of atherosclerosis. These include inhibition of vascular smooth muscle cell (SMC) proliferation and migration; inhibition of calcium influx into the vascular wall; reduction of extracellular matrix synthesis; promotion of uptake and breakdown of low-density lipoproteins; protection of lipoproteins from oxidative modification; maintenance of endothelial cell function; inhibition of platelet activation; and reduction of blood pressure. Although some of these effects are only seen at high drug concentrations, the great majority of reports indicate that CCBs can attenuate atherogenesis in animal models, notably the cholesterol-fed rabbit.

The pathogenesis of atherosclerosis.

The hypothesis that atherosclerosis is a 'response to injury' is now generally accepted. This paper briefly reviews factors that can damage the vascular endothelium plus the formation of fatty streak lesions, thrombogenic surfaces, fibrous plaques and complex advanced lesions of atherosclerosis.

The use of cyclical etidronate in osteoporosis: changes after completion of 3 years treatment.

An open study over 4 yr has been conducted to determine the efficacy of cyclical etidronate treatment in patients from the community, with osteoporosis and in those at risk who attended an osteoporosis clinic; and to clarify whether bone remodelling returns to baseline values and bone mass is maintained after completion of a 3 yr course of treatment. One hundred and fifteen female patients, with and without osteoporotic fractures (n = 62 and 53, respectively), who were unsuitable for, or declined, hormone replacement therapy, received 3 yr cyclical etidronate treatment (400 mg etidronate disodium for 14 days followed by 500 mg elemental calcium for 76 days repeated in 3-monthly cycles) and 1 yr treatment-free follow-up. There was an overall increase in lumbar spine bone density (patients without fractures 2.

Clinical experience, performance in final examinations, and learning style in medical students: prospective study.

Objective: To assess whether the clinical experience of undergraduate medical students relates to their performance in final examinations and whether learning styles relate either to final examination performance or to the extent of clinical experience.

Design: Prospective, longitudinal study of two cohorts of medical students assessed by questionnaire at time of application to medical school and by questionnaire and university examination at the end of their final clinical year.

Subjects: Two cohorts of students who had applied to St Mary's Hospital Medical School during 1980 (n = 1478) and 1985 (n = 2399) for admission in 1981 and 1986 respectively.