Greater attention has been recently paid to the role of certain strains of streptococcus as an etiologic agent of Behçet's disease, in which T cell abnormalities are considered to be involved. We therefore examined whether T cells from patients with Behçet's disease might to be stimulated by Streptococcus sanguis-related antigen (RRE KTH-1 antigens). T cells from 17 patients with Behcet's disease, but not those from 13 healthy individuals or from 13 patients with other rheumatic diseases, were stimulated to produce greater amounts of interleukin 6 (IL6) by addition of RRE KTH-1 antigens [stimulation index: 3.96 +/- 0.56 and 1.35 +/- 0.28 or 1.83 +/- 0.43 (mean +/- SEM), respectively]. The IL6 production by T cells required the presence of either fresh or paraformaldehyde-fixed monocytes. The enhancement of T cell IL6 production was not related to the presence of HLA-B51, which has been shown to be frequently associated with Behçet's disease. These results indicate that T cells from patients with Behçet's disease are stimulated by streptococcal antigens to produce IL6 through T cell-monocyte interactions in which binding of the antigens to monocytes, but not necessarily processing of the antigens by monocytes, is involved. Moreover, RRE KTH-1 antigens as well as Escherichia coli-derived antigens also enhanced the production of interferon-gamma by T cells from patients with Behçet's disease. The data thus suggest that T cell hypersensitivity to several bacterial antigens may play a central role in the pathogenesis of Behçet's disease.

The potentiating effect of the soluble factors released from normal or diseased lymphocytes on neutrophil functions were investigated in the presence or absence of mitogens and wall preparations of Streptococcus pyogenes. When normal T lymphocyte populations were stimulated with T cell mitogens or with streptococcal preparations, the supernatants from these cultures potentiated neutrophil chemotaxis, phagocytosis and O2- generation. Upon gel-filtration of these stimulated lymphocyte supernatants, the neutrophil-potentiating activity was inactivated by trypsin or by a 30-min incubation at 130 degrees C, but was not affected by acid treatment at pH 2 or heat treatment at 56 degrees C for 60 min. Its activity was almost not affected by antisera against human interleukin-1, interleukin-2, interferon-gamma or tumour necrosis factor. With the stimulation of T cell mitogens, the supernatants released from the lymphocytes of not only the patients with Behçet's disease but also healthy and diseased controls enhanced neutrophil functions. However, supernatants from streptococcal preparation-stimulated lymphocytes from patients with Behçet's disease had a higher potentiating effect on neutrophil functions. Our study suggests that the enhanced neutrophil functions in patients with Behçet's disease may be related to an abnormally high level of circulating activated T cells in these patients.

Phospholipid methylation and phospholipase A2 activation in the membrane of neutrophils and lymphocytes, which participate in the induction of cell activation, were assessed in patients with Behçet's disease, systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). [3H-methyl] incorporation and phospholipase A2 activity of neutrophils from active cases of Behçet's disease and RA were significantly increased compared with normal controls. In lymphocytes from the patients with active Behçet's disease and RA, a significant increase in methyltransferase activity and a marked enhancement of phospholipase activity were found. A modest increase in these two membrane phospholipid enzyme activities was observed in lymphocytes of patients with active SLE. In addition, these enzyme activities were significantly enhanced in normal leukocytes preincubated with serum from patients with active SLE and malignant RA. The potentiated functions of neutrophils and lymphocyte abnormalities in the patients tested thus seem to be at least partly due to an increase in these enzymatic activities in the cell membrane.

Phospholipid base exchange and cholinephosphotransferase (CPT) and ethanolaminephosphotransferase (EPT) activities were assessed in the membranes of neutrophils or lymphocytes from patients with various inflammatory disorders. Ethanolamine exchange activity was significantly enhanced in both neutrophils and lymphocytes from patients with active Behçet's disease, active systemic lupus erythematosus (SLE), and severe bacterial infections and slightly enhanced in those from patients with active rheumatoid arthritis (RA), compared with healthy controls. No abnormal findings were found in CPT, EPT, or serine or choline base exchange activities in the leukocytes from any of the diseased groups tested or in the ethanolamine exchange activity of patients with severe viral infections and inactive SLE, RA, and Behçet's disease. The authors have recently demonstrated the enhancement of transmethylation and phospholipase A2 activity in human leukocyte membranes at the height of inflammatory disease states, as well as the activation of leukocyte ethanolamine exchange by bioactive stimulants. These data postulate that phosphatidylethanolamine synthesis by the base exchange reaction may be the precursor of transmethylation and its subsequent activation of phospholipase A2, leading to the induction of arachidonic acid cascade.

The effect of an immunosuppressive drug, cyclosporin A, and dexamethasone was assessed on the enzymatic reactions of membrane phospholipid in normal human lymphocytes and neutrophils. Incubation for 20 min with cyclosporin A markedly suppressed, in a dose dependent manner, phospholipase A2 activity and the release of prostaglandin E2 in lymphocytes, and slightly those in neutrophils, while no inhibition of phosphatidylethanolamine (PE)-N methyltransferase activity was observed. Choline phosphotransferase (CPT) activity was not inhibited by the drug, either. These inhibitory effects on enzyme activities of membrane phospholipid are similar to those of dexamethasone, although different incubation time of the drug was required to induce inhibitory effects. These findings suggest that cyclosporin A acts upon early membrane events in the activation of cells involved in inflammatory reactions; they further suggest that suppression of immune response by cyclosporin A is at least partly due to inhibition of phospholipase A2 in the plasma membrane of inflammatory cells. This inhibition reduces the production of cell membrane lyso-phosphatidylcholine (PC) and arachidonic acid from PC, which is produced by transmethylation of PE and cytidine diphosphate (CDP) choline pathway of which the last reaction to PC is mediated by CPT.

The functions of phagocytes are enhanced in patients with Behçet's disease, therefore, we investigated the neutrophil-derived oxygen intermediates (OI) and lysosomal enzymes from 17 patients receiving glucocorticosteroids (steroids) and colchicine. Cultured endothelial cells were incubated with neutrophils to assess tissue injury. In cases of the complete type, in the active stage of the disease, OI production was markedly increased. The other patients showed significantly higher OI and higher lysosomal enzyme levels than patients with other diseases (controls) receiving drug therapy. Cytotoxicity tests showed that the 51Cr release was also significantly higher. The destruction of desmosomes and cell deformation were demonstrated electron microscopically. The simultaneous addition of superoxide dismutase and catalase in the cell culture decreased the 51Cr release to control levels. These findings suggest that neutrophils from patients with Behçet's disease generate high levels of OI, resulting in endothelial tissue damage.

Behçet's disease is characterized by three primary components: iridocyclitis (historically with hypopyon), aphthous lesions in the mouth, and ulceration of the genitalia. Erythema nodosum, arthropathy and thrombophlebitis often accompany these manifestations, but the ocular symptoms may be the most important and serious manifestations of the disease. Central nervous system involvement, most often due to necrotizing vasculitis, may be the most protean manifestation of the disease, leading to death. The frequency of ocular manifestations is 70-85% in patients with the disease; the underlying disease mechanism in all organ systems is an occlusive vasculitis. Although the most common ocular symptom is that of anterior uveitis, often with hypopyon as a very late sign, the presence of necrotizing retinal vascular lesions is well known and often obscured by the severity of the anterior reaction. Definitions, incidence, clinical characteristics, differential diagnosis, and management of Behçet's ocular disease are discussed, as are the interrelationships of the different organ manifestations. The ophthalmologist should be familiar with the full spectrum of disease presentation since he or she may be the first physician to encounter the Behçet's patient.

A family with features of the mucocutaneous ocular syndrome is described. A 4-generation study reveals that the condition has been inherited as an autosomal dominant trait with variable expressivity. Psychiatric symptoms and myalgia have been prominent features peculiar to our patients.

Behçet's syndrome is reported in a family of which four generations have so far been affected. The index patient also exhibited an unusual schizo-affective disorder. The histocompatibility antigen haplotype 1-17 was common to four with the disease. Genetic transmission may be responsible for the familial nature of the syndrome and the associated schizophrenia.

Twenty thousand Arabs of various nationalities living in Kuwait have been investigated over the past 5 years; 5,470 (27%) manifested recurrent aphthous ulcerations (RAU). Non-Kuwaiti Arabs were affected more the Kuwaitis and the prevalence of the disease was respectively 35% and 18%. Among Kuwaitis, only 5% of the Bedouins manifested the diseases whereas 22% of urbanized Arabs were affected. The ratio of the affected females to males in this study was 6:5. The clinical course of RAU in Arabs was similar to that reported in other populations. Various environmental factors such as stressful conditions, social tradition and obligations, and the allergenic Arabic food seemed to affect the prevalence of RAU in different Arab communities.

In the prickle-cell layer of the oral epithelium of recurrent aphthous ulceration (RAU) the reticuloid cells with homogeneous, electron-lucent nuclei were attached to the degenerated prickle cells and ingested the cytoplasm of the prickle cells. The reticuloid cells came in contact with small lymphocytes, to which the immunologic information was transferred, inducing them to undergo blast transformation. Lymphoid cells, corresponding to T-cells, may produce a cytotoxic factor, since the prickle cells ultimately undergo degeneration. These changes are consistent with those of delayed hypersensitivity reactions. The cytoplasm of prickle cells apparently acts as an autoantigen. In Behçet's syndrome the macrophages were encountered in the epithelium. Other consequences were quite similar to those of RAU. The nucleus of the macrophage is more electron dense and has condensed chromatin along with the nuclear membrane. This can be a difference between Behçet's syndrome and RAU only at the initial stage of the diseases.

The field of oral medicine is fundamental to the practice of general medicine as well as dentistry, oral surgery, and other special fields of medicine concerned with diseases of organs beneath the oral cavity. Disorders of the oral mucosa may reflect many dermal and internal diseases, and may focus the physician's diagnostic attention to systemic pathological conditions which otherwise could be misdiagnosed. As to their morphological appearance, however, the oral mucosa shows other forms of reactivity than the skin. When the dermal and oral manifestations of many skin diseases are compared the influence of distinct local factors on the intraoral clinical picture becomes evident. This comparative view, as well as the dermatologist's practical experience that many dermatoses either spread to, or even are restricted to the oral mucosa, may explain why most dermatologists are very interested in oral diagnosis. In this report, the interdisciplinary view and some aspects of clinical stomatology are stressed which are of actual interest in oral diagnosis and therapy. The following topics are dealt with: Diseases with aphthous lesions, Allergic reactions to drugs, Pemphigus and pemphigoid disorders, Oral infections by Candida albicans, Melkersson-Rosenthal syndrome, Lingual anomalies of different types, Leukoplakias.

The gastrointestinal involvement and immunological findings in 16 patients with Behçet's disease are described. Four of 15 biopsy specimens of jejunal mucosa showed marked lymphangiectasia in the lamina propria similar to the appearance which was thought to be a characteristic finding in protein-losing enteropathy. None of the patients had hypoproteinaemia. Increases in serum immunoglobulin IgA were proved in six of 15 cases; in IgM, five of 15; and in IgG, one of 15. Electron microscopic studies showed that there were thousands of precipitated lymph protein bodies in the extracellular spaces of the lamina propria. Ulcers and healed ulcers of the large intestine were studied by light microscopy.