Basiliximab (anti-CD25) in combination with steroids may be an effective new treatment for steroid-resistant ulcerative colitis.

Background: Steroid resistance represents a major clinical problem in the treatment of ulcerative colitis. In vitro, interleukin-2 renders lymphocytes steroid resistant.

Aim: To explore the therapeutic potential of interleukin-2 receptor blockade in steroid-resistant ulcerative colitis with both in vitro measures and a pilot in vivo study.

Humoral and cellular immune responses to proinsulin in adults with newly diagnosed type 1 diabetes.

Background: Type 1 diabetes (T1D) is an autoimmune disease characterized by immunity against pancreatic islet-derived proteins. The object of this study was to measure antibody and T-cell responses against proinsulin (PI), an islet-derived protein, and to map its dominant T-cell epitopes.

Methods: Antibody responses to proinsulin, insulin, glutamic acid decarboxylase (GAD), protein tyrosine phosphatase IA-2 and islet-cell antigen were measured in 116 newly diagnosed diabetic subjects aged 16 to 40 years.

Psychological well-being in patients on 'adequate' doses of l-thyroxine: results of a large, controlled community-based questionnaire study.

Objective: Over 1% of the UK population is receiving thyroid hormone replacement with l-thyroxine (T4). However, many patients complain of persistent lethargy and related symptoms on T4 even with normal TSH levels. To date there has been no large study to determine whether this is related to thyroxine replacement or coincidental psychological morbidity.

Reproducibility of individualized coronary heart disease risk calculations in patients with diabetes mellitus.

Aims: To determine prospectively, the reproducibility of individualized coronary heart disease (CHD) risk estimations in a high-risk (diabetic) population.

Methods: One hundred and three patients attending a hospital diabetes clinic who were in the primary prevention category for CHD had measurements of cholesterol, HDL-cholesterol and systolic blood pressure (SBP) performed in one of 13 general practices and then 2 weeks later in the hospital clinic. The data were combined with age, sex, smoking history and diabetic status data to produce a 10-year CHD risk estimate for each occasion using the Framingham algorithm.

Characterization of the T-cell response to coxsackievirus B4: evidence that effector memory cells predominate in patients with type 1 diabetes.

Most of the evidence linking enterovirus (EV) infection with the development and/or acceleration of type 1 diabetes is indirect. Few studies have examined T-cell responses to these viruses, and therefore the nature of the viral targets and the immune cells involved in antiviral responses remain unclear. In the present study, we examined the characteristics of the T-cell response to the EV Coxsackievirus B4 (CVB4) in patients with type 1 diabetes and healthy control subjects.

Dendritic cell-based proliferative assays of peripheral T cell responses to tetanus toxoid.

Antigen-specific proliferative responses of peripheral blood T cells are widely used in humans to study the T cell compartment. However, responses to autoantigens are often weak and poorly reproducible. Here we show, using a test recall antigen (tetanus toxoid), that absolute levels of proliferation, minimally detectable antigen doses, and/or ability to detect statistically significant responses can be enhanced using in vitro-generated autologous dendritic cells as antigen presenting cells.

Interpretation of thyroid function tests.

The introduction of sensitive thyrotropin assays and free thyroid hormone measurements has simplified the interpretation of thyroid function tests. However, important pitfalls and difficult cases still exist. In this review, thyroid function test results are grouped into six different patterns.

T cell activation by coxsackievirus B4 antigens in type 1 diabetes mellitus: evidence for selective TCR Vbeta usage without superantigenic activity.

Numerous clinical and epidemiological studies link enteroviruses such as the Coxsackie virus group with the autoimmune disease type 1 diabetes mellitus (DM). In addition, there are reports that patients with type 1 DM are characterized by skewing of TCR Vbeta chain selection among peripheral blood and intraislet T lymphocytes. To examine these issues, we analyzed TCR Vbeta chain-specific up-regulation of the early T cell activation marker, CD69, on CD4 T cells after incubation with Coxsackievirus B4 (CVB4) Ags.

Thyroid autoantibodies.

Although assays to detect thyroid autoantibodies have been available for more than 40 years, their place in the clinical management of thyroid disease has remained controversial; however, novel automated detection techniques using recombinant antigens are increasing the sensitivity and specificity of the assays, particularly for antibodies to the TSH receptor. In addition, new antigenic targets have been defined including the sodium-iodide symporter and four eye muscle proteins targeted in Graves' ophthalmopathy. This article summarizes the immunobiology, assay methodology and prevalence in thyroid diseases of each of the major thyroid autoantibodies before discussing the clinical indications for their use in thyroid diseases.

Effective formation of major histocompatibility complex class II-peptide complexes from endogenous antigen by thyroid epithelial cells.

In autoimmune thyroid disease, thyroid epithelial cells (TEC) express major histocompatibility complex (MHC) class II molecules, potentially enabling them to present thyroid self-antigens to CD4-positive T cells. However, despite this, TEC may fail to present endogenous antigen as a result of limited processing or MHC class II loading capacity, or inadequate MHC class II levels. We addressed these issues using the cloned rat TEC line, Fischer rat thyroid cell line (FRTL5), which was transfected using an adenoviral expression vector that expressed ovalbumin (OVA) as an integral membrane protein.

Wide variation in lymphocyte steroid sensitivity among healthy human volunteers.

Steroids are frequently used to treat inflammatory conditions in which lymphocytes play a role. We have recently shown that in severe ulcerative colitis, treatment outcome correlates better with in vitro estimates of lymphocyte steroid sensitivity (LSS) than with disease severity. This lead us to examine the range and variability of LSS in the healthy population.

Predicting therapeutic outcome in severe ulcerative colitis by measuring in vitro steroid sensitivity of proliferating peripheral blood lymphocytes.

Background: Up to 29% of patients with severe ulcerative colitis (UC) fail to respond to steroid treatment and require surgery. Previous studies have failed to show a clear correlation between failure of steroid treatment in severe UC and measures of disease severity. The reasons for treatment failure therefore remain unknown.

In vitro measurement of lymphocyte steroid sensitivity: lack of agreement between whole blood culture and separated lymphocyte culture.

The use of a whole blood culture to measure steroid sensitivity has previously been compared to the use of a separated lymphocyte assay. Good correlation between the two methods was reported. However the number of subjects studied appears to have been small and no patients with steroid resistance were studied.

Effects of Acute Stress or Centrally Injected Interleukin-1beta on Neuropeptide Expression in the Immune System.

Acute stress stimulates the expression and release of corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) from the hypothalamus, and the pro-opiomelanocortin products beta-endorphin and ACTH from the anterior pituitary. These neuropeptides are also expressed in immune tissues, and it has been proposed that they may modulate immune responses to stress through paracrine mechanisms. We subjected rats to restraint stress or central injection of interleukin (IL)-1beta to determine whether these acute stimuli can alter the expression of neuropeptides in the spleen and thymus.