Distribution of interleukin 1 receptor antagonist protein (IRAP), interleukin 1 receptor, and interleukin 1 alpha in normal and psoriatic skin. Decreased expression of IRAP in psoriatic lesional epidermis.

The distribution of interleukin 1 alpha (IL-1 alpha), type 1 interleukin 1 receptor (IL-1R), and the interleukin 1 receptor antagonist protein (IRAP), was investigated in biopsies of normal skin, and in uninvolved and lesional skin of patients with psoriasis, using specific monoclonal antibodies. We report the novel finding that IRAP is distributed throughout the living layers of the epidermis in normal skin, and is also associated with sebaceous glands and eccrine sweat glands. Our finding that the inhibitor protein IRAP is present in areas where the pro-inflammatory cytokine IL-1 alpha is distributed provides strong evidence in favour of a cytokine regulatory system in normal skin.

Detection of cytokines at the cartilage/pannus junction in patients with rheumatoid arthritis: implications for the role of cytokines in cartilage destruction and repair.

Cytokine release at the cartilage/pannus junction (CPJ) may be involved in cartilage destruction and tissue repair in rheumatoid arthritis (RA). Tissue samples of CPJ from 12 RA patients were examined for the presence of cytokines using immunohistochemical techniques with immunoaffinity purified F(ab')2 antibodies raised against recombinant human cytokines. Twenty-four areas of distinct CPJ at which a discrete junction between cartilage and overlying pannus exists were observed.

Localization of tumor necrosis factor receptors in the synovial tissue and cartilage-pannus junction in patients with rheumatoid arthritis. Implications for local actions of tumor necrosis factor alpha.

Objective: We have previously described the location of tumor necrosis factor alpha (TNF alpha)-producing cells in synovial tissue and cartilage-pannus junction in rheumatoid arthritis (RA). To further understand the local actions of TNF alpha, we investigated the expression of TNF receptors (TNF-R) on cells in the same compartments in patients with RA.

Methods: The expression of both p55 TNF-R and p75 TNF-R was determined using alkaline phosphatase-conjugated mouse anti-alkaline phosphatase (APAAP) and double immunofluorescence staining techniques with monoclonal antibodies.

Increased levels of soluble tumor necrosis factor receptors in the sera and synovial fluid of patients with rheumatic diseases.

Objective: Recently, 2 classes of cytokine inhibitors have been defined at the molecular level. The largest group comprises the extracellular domains of cell surface cytokine receptors, and includes both tumor necrosis factor receptors (TNF-R). The present study was conducted to investigate the role of TNF inhibitors in arthritis.

HER2 (c-erbB-2) oncoprotein expression in colorectal adenocarcinoma: an immunohistological study using three different antibodies.

Paraffin wax sections of 70 surgically resected colorectal adenocarcinomas were examined for the overexpression of HER2/c-erbB-2 oncoprotein using three different specific antibodies and the avidin-biotin immunoperoxidase technique. The patients included 38 men and 32 women aged between 47 and 80 years. The tumours were derived from various parts of the large intestinal tract, and represented all three stages of Dukes' classification and the three histological grades of differentiation.

Synergism of glucocorticoids with granulocyte macrophage colony stimulating factor (GM-CSF) but not interferon gamma (IFN-gamma) or interleukin-4 (IL-4) on induction of HLA class II expression on human monocytes.

Peripheral blood monocytes from up to 13 normal donors were stimulated with the cytokines interferon gamma (IFN-gamma), interleukin 4 (IL-4) and granulocyte macrophage-colony stimulating factor (GM-CSF) in the presence or absence of dexamethasone (Dex), and the effects on HLA class II (HLA-DR, DP and DQ) expression studied. Dex markedly augmented HLA-DR, DP and DQ levels induced by GM-CSF, in all samples tested. Particularly striking were the effects on HLA-DQ expression, since stimulation with a combination of Dex and GM-CSF induced markedly higher levels of HLA-DQ antigen than stimulation with IFN-gamma.

Upregulation of HLA class II, but not intercellular adhesion molecule 1 (ICAM-1) by granulocyte-macrophage colony stimulating factor (GM-CSF) or interleukin-3 (IL-3) in synergy with dexamethasone.

In this study we have compared the effects of granulocyte macrophage colony stimulating factor (GM-CSF) on purified normal blood monocytes, with two other haemopoietic growth factors, Interleukin (IL-) 3 and Macrophage (M-)CSF on HLA class I, class II and intercellular adhesion molecule 1 (ICAM-1) expression in the presence and absence of dexamethasone (Dex). IL-3 alone, like GM-CSF, was a weak inducer of HLA class II expression but in combination with Dex markedly enhanced HLA-DR, DP and DQ expression. Similar changes were observed for HLA class I expression.

Enhanced expression of tumor necrosis factor receptor mRNA and protein in mononuclear cells isolated from rheumatoid arthritis synovial joints.

We previously proposed the hypothesis that the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA) based on our observations that it is the dominant inducer of interleukin-1 (IL-1) and granulocyte-macrophage colony-stimulating factor (GM-CSF) production in RA synovial joint mononuclear (MNC) cells in culture. Since TNF-alpha acts via two membrane receptors, we have extended those studies to investigate the distribution of the p55 and p75 TNF receptors (TNF-R) in RA tissue. Surface receptor expression was quantitated by flow cytometry using monoclonal antibodies specific to the p55 (HTR-9) and the p75 (UTR-1) TNF-R.

Neuromyotonia: report of a case.

Neuromyotonia is a rare condition of peripheral nerve dysfunction characterized by the signs of motor nerve hyperactivity, namely, myokymia, fasciculations, and muscular stiffness. Relaxation of voluntary muscle contraction is delayed, and fluid movements are impaired to a variable degree. Signs of sensory involvement are less frequent.

TNF alpha--a pivotal role in rheumatoid arthritis?

This review seeks to describe data which support the concept that TNF alpha has a pivotal role in the pathogenesis of RA. There is now compelling evidence from in vitro studies and in animal models that this is the case. The in vitro studies suggest that the direct pathogenic effects of TNF alpha are amplified by its potential to act as a potent paracrine molecule, by inducing other pro-inflammatory molecules such as IL-1, and GM-CSF.

T cell activation and antigen presentation in human thyroid autoimmunity.

In 1983, a hypothesis concerning the relevance of class II expression and antigen presentation to the induction and maintenance of endocrine autoimmunity was published. This article reviews the evidence that has been marshalled to support this concept, both in man, chiefly in Graves' disease, and in murine systems. New data concerning the multiplicity of thyroid autoantigens recognized by in vivo activated thyroid infiltrating T cells are compatible with this concept since the thyroid epithelial cells are the source of these antigens.

T-cell-targeted immunotherapy.

The pace of T-cell research is matched only by the speed with which fundamental advances are being developed as new therapies. This report from a recent meeting updates developments in a number of immunointervention strategies.

Detection of in vivo production of tumour necrosis factor-alpha by human thyroid epithelial cells.

We have established previously that human thyroid epithelial cells (TEC) from patients with autoimmune thyroiditis are able to synthesize cytokines, such as interleukin-1 (IL-1) and interleukin-6 (IL-6). This paper examines TEC in sections from autoimmune thyroiditis for the in vivo production of tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) using the combined techniques of in situ hybridization and immunohistochemistry. Thyroid tissue from patients with Graves' disease, Hashimoto's disease and non-toxic goitre was examined and both mRNA and the protein of TNF-alpha were detected in TEC on frozen sections.

[Droperidol versus metoclopramide. Prevention of emesis following strabismus surgery in children].

Vomiting after strabismus surgery is a major problem that remains as yet unsolved, especially in children. Droperidol and metoclopramide, both known as powerful antiemetic drugs, were compared in this study. METHODS.

Development of humanized bispecific antibodies reactive with cytotoxic lymphocytes and tumor cells overexpressing the HER2 protooncogene.

The HER2 protooncogene encodes a 185-kD transmembrane phosphoglycoproteins, human epidermal growth factor receptor 2 (p185HER2), whose amplified expression on the cell surface can lead to malignant transformation. Overexpression of HER2/p185HER2 is strongly correlated with progression of human ovarian and breast carcinomas. Recent studies have shown that human T cells can be targeted with bispecific antibody to react against human tumor cells in vitro.

[Bourneville tuberous sclerosis manifested by prenatal finding of intracardiac tumors].

Neonatal cardiac rhabdomyoma is the most frequent cardiac tumour in the newborn, and a classical way to diagnose tuberous sclerosis (Bourneville's disease). The authors report 4 cases, including 2 antenatal diagnosis: 2 of them had arrhythmia, one with asystolic cardiac failure and the other with cyanosis due to a right-left shunt; the tumour was asymptomatic in the 2 others. The 4 babies had clinical and radiological neurologic signs of tuberous sclerosis, initially or during the course of the disease.

[Neonatal Campylobacter fetus septicemia: a case secondary to maternal-fetal contamination].

A favourable outcome of a severe Cambylobacter fetus sepsis in a neonate is reported. The transmission was probably vertical. His mother experienced diarrhoea 15 days before birth.

Evaluation of the role of cytokines in autoimmune disease: the importance of TNF alpha in rheumatoid arthritis.

Cytokines and growth factors are involved in all important biological processes. Hence it is anticipated that they will be of importance in autoimmune disease. The pathogenesis of autoimmune diseases involves a number of stages, initiation, perpetuation and tissue damage, each of which involves different cell and molecular interactions.

Regulatory interactions among autologous T cell clones. Human bifunctional T cell clones regulate the activity of an autologous T cell clone.

In contrast to the ease of cloning and characterizing, at the molecular level, helper and cytotoxic T cells, suppressor T cells remain an enigma, and their existence as discrete entities is being increasingly challenged. Here we review evidence that CD4+ regulatory clones, capable of expressing both helper and suppressor functions, may account for much of the suppressor function. It is suggested that a single T cell clone, depending on the signals it receives from its environment, may release either helper or suppressor cytokines.

Transforming growth factor-beta 1 in rheumatoid synovial membrane and cartilage/pannus junction.

Transforming growth factor (TGF)-beta has been shown to promote tissue repair and have immunosuppressive actions, and has been proposed to have a role in rheumatoid arthritis (RA). Using immunohistochemical techniques with rabbit F(ab')2 antibodies raised against recombinant human TGF-beta 1, we have detected TGF-beta 1 in the synovial tissue and cartilage/pannus junction (CPJ) from 18/18 patients with RA. TGF-beta 1 was found predominantly in the thickened synovial lining layer in RA, but also detected in a perivascular pattern in the synovial interstitium as well as in occasional cells in the lymphoid aggregates.

Expression of granulocyte-macrophage colony-stimulating factor in rheumatoid arthritis: regulation by tumor necrosis factor-alpha.

Granulocyte-macrophage colony-stimulating factor (GM-CSF), in addition to being a growth factor for granulocytes and macrophages, is an activator of cells of the monocyte/macrophage lineage and induces HLA class II expression and cytokine synthesis in these target cells. Macrophage activation and class II expression are prominent features in rheumatoid arthritis (RA) joints, but the mechanism of their stimulation is not understood, since interferon-gamma, the major stimulus of class II expression, is not usually detectable at the protein level in synovial cell culture supernatants. We have, therefore, studied GM-CSF expression in cultures of cells derived from joints affected by RA and osteoarthritis (OA), and show that GM-CSF is produced spontaneously both by RA synovial cells and to a lesser extent by OA synovial cells in the absence of extrinsic stimuli.

Platelet-derived interleukin 1 induces human endothelial adhesion molecule expression and cytokine production.

Interleukin 1 (IL-1) plays a central role in the regulation of the body's response to infectious and inflammatory stimuli. Recent evidence has shown that human platelets express a cell associated form of this proinflammatory cytokine very rapidly following activation. Since one of the earliest events in inflammation is frequently the rapid adhesion of platelets to injured endothelium, it was of interest to determine whether platelets express IL-1 in a functionally relevant form that can alter the phenotype of human endothelial cells in vitro.

Localization of tumor necrosis factor alpha in synovial tissues and at the cartilage-pannus junction in patients with rheumatoid arthritis.

Using immunoaffinity-purified polyclonal anti-human recombinant tumor necrosis factor alpha (TNF alpha) F(ab')2 fragments and immunohistochemical techniques, the cells that make TNF alpha were localized in the inflamed synovial tissue of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Anti-TNF alpha antibody-stained cells were demonstrated in 9 of 11 RA and 2 of 4 OA but none of 5 normal synovial membranes examined. In RA, 26-64% of the lining layer cells were positive for TNF alpha.