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Animal models for Behcet syndrome (BS) can be divided according to the proposed etiological paradigms. These include environmental pollution and infectious (bacterial and viral) models, as well as various autoimmune and transgenic animal models. The environmental pollution model, though resembles the multisystem symptoms of BS, has limitations to become utilized as a model for the disease since it is difficult to produce, and the onset of symptoms appears erratically in a wide time range. The Streptococcal models have similarity only to the eye involvement in BS. This model is simple to induce with high rate of homogeneity. The HSV model has multisystem manifestations resembling BS; it has a moderate reproducibility. The autoimmune models utilizing S-Ag and IRBP are monosymptomatic models of BS-like uveitis. Those models are easy to induce, and extensive studies elucidated some of the immunological characteristics of BS including the paradigm of anti-HLA autoimmunity. The α-tropomyosin model shares some clinical features of BS. This model has a potential to become a useful autoimmune model for BS. The only published trial to establish a transgenic model for BS did not show any significant similarity to the human disease except a hyper-responsiveness of neutrophils.

A catalase-positive, rod-shaped, non-proteolytic, non-motile, anaerobic bacterial strain, designated B086562T, was isolated from a blood culture of an 84-year-old male patient in Israel. According to 16S rRNA gene sequence phylogeny, this strain has no known close relatives among recognized bacteria but should be placed within the family Lachnospiraceae . The most closely related recognized bacteria were from the ‘ Clostridium clostridioforme group’: C. clostridioforme (92.4 %) and Clostridium bolteae (92.3 %). The isolate produced butyrate, lactate, acetate and succinate as major metabolic end products. The major fatty acids were C16 : 0 and C18 : 1 cis 9 DMA and the DNA G+C content was 46.0 mol%. On the basis of the phenotypic properties and phylogenetic distinctiveness, the blood isolate represents a novel species of a new genus in the family Lachnospiraceae , for which the name Eisenbergiella tayi gen. nov., sp. nov. is proposed. The type strain of Eisenbergiella tayi is B086562T ( = LMG 27400T = DSM 26961T = ATCC BAA-2558T).

Behcet's disease (BD) is a multisystem disease, in which recurrent aphthous stomatitis (RAS) is a universal finding. We studied the expression of RAS in patients with BD, and the correlation between major or minor RAS and systemic expression and severity of the disease. Thirty-five patients with BD were studied, of whom 13 (37%) had major, 21 (60%) had minor and one (3%) had herpetiform RAS. The frequency of major RAS was significantly higher compared with a control group of patients with idiopathic RAS (37% vs 9%, P < 0.05). The BD patients with major RAS had significantly more relapses of oral ulceration in a year, higher numbers of oral ulcers per relapse, and longer duration of aphthous episodes, compared with patients with minor RAS. Oral ulcers also appeared at a significantly younger age in patients with major than with minor RAS. However, the systemic expression of the disease, as well as the disease severity score, were similar in patients with major and minor RAS. The results of this study indicate that major RAS is common in patients with BD, and is associated with a more severe, repeated and prolonged oral disease. Nevertheless, the presence of major RAS in BD does not predict a more severe systemic illness.

Benign familial leukopenia was found in 75 of 200 healthy Yemenite Jews examined. The leukopenia was not a constant finding and was not associated with a tendency toward infection. HLA typing showed no significant differences in the frequency of the various HLA antigens between the subjects with and without leukopenia. No similarity was found between the HLA of the Yemenite Jews with leukopenia and that reported in black Africans with benign familial leukopenia. The suggestion of a genetic contribution from African blacks to Yemenite Jews is not supported by these results. The question remains to be answered whether the familial leukopenia in Yemenite Jews and black Africans is the result of a mutation.

Behcet's disease (BD) has a higher prevalence in countries along the ancient silk route, but the actual prevalence in Israel is unknown. We evaluated the occurrence and clinical expression of BD in the northern region of Israel: in the whole population and by ethnic groups. The sample included all adult patients with BD (International Study Group criteria) treated at three medical centers in northern Israel. Patient data were collected by file review and physician survey. Relevant demographic data for the population served by the medical centers were obtained from the official Israeli authorities. A total of 112 patients were identified. The overall prevalence of BD was 15.2/100,000 and was similar in men and women. The prevalence rates among the Jewish, Arab, and Druze populations were 8.6, 26.2, and 146.4 per 100,000, respectively. Age at disease onset was similar in all ethnic groups and significantly lower in males (28.6+/-9.7 vs 32.9+/-11.3, p=0.03). There were no differences in disease manifestations by sex or ethnicity. All Druze patients were HLA-B5 positive, compared to 80.8% of the Arab patients and 72.0% of the Jewish patients. Recurrent oral ulcers in family members were more common in Arab patients (p=0.004). The BD severity index was significantly lower in Druze patients (p=0.05), mainly in males (p=0.03). This study confirms the high prevalence of BD in Israel and the variability in disease rates and expression by ethnic origin. Our findings, particularly regarding the Druze population, call for further field surveys and genetic studies.

Behcet's disease (BD) is a chronic systemic inflammatory disease of unknown etiology. Its prevalence has a unique geographic distribution from the Far East to the Mediterranean basin. In addition, the majority of patients carry the class I HLA-B51 gene as a genetic marker. Therefore, the proposed etiological factors might be environmental, infectious, genetic, autoimmune and a combination thereof. A crucial review of the current experimental animal models for BD and their relevance to the human disease are presented.

Probiotic bacteria have beneficial effects in infectious and inflammatory diseases, principally in bowel disorders. In the case of chronic progressive autoimmune arthritides, a major goal of treatment is to reduce inflammation. We hypothesized that probiotic bacteria would ameliorate inflammation found in arthritis models. To assess this effect, Lewis rats were injected with 50 microg bovine alpha-tropomyosin (TRM) or complete Freund's adjuvant (CFA) to induce tropomyosin arthritis (TA) or adjuvant arthritis (AA), respectively. In both models, the rats were divided into 6 groups and fed 0.5 mL/d of the following suspensions: 1) heat-killed Lactobacillus GG (LGG) bacteria; 2) live LGG, both 10(11) colony-forming units (cfu)/L; 3) sterilized milk; 4) plain yogurt; 5) yogurt containing 10(11) cfu/L LGG; or 6) sterilized water. In the disease-prevention experiments, feeding started 1 wk before or after disease induction. In the therapeutic experiments, feeding was initiated at the onset of clinical arthritis. In all experiments, there were significant interactions between time and treatment (P < 0.001), except for milk, which had no effect in the therapeutic experiment. Histologically, rats fed yogurt containing LGG had a milder inflammation in all experiments (P < 0.05), whereas rats fed plain yogurt exhibited a moderate inflammatory score only in the prevention experiments. Anti-TRM antibody titers were not affected by any of the treatments in any of the experiments. Ingestion of live or heat-killed human LGG had a clinically beneficial effect on experimental arthritis. Our observation of the remarkable preventive and curative effect on arthritis using commercial yogurts containing lactobacilli, especially LGG, suggests the need for investigation of these agents in arthritic patients.

The anti-inflammatory effect of methotrexate (MTX) is mediated by the increasing extracellular concentration of adenosine. The response of the immune system to activation of cell membrane subclass receptors for adenosine initiates intracellular signaling pathways, which causes immunomodulatory responses. To test the direct immunomodulatory effects of systemic administration of adenosine on animal model of inflammation, zymosan induced arthritis (ZIA) in mice was employed. Sterile zymosan (30 mg) was injected directly into the knee cleft of 60 mice, divided into 3 equal groups. The experimental groups received, every second day, 0, 0.25, and 0.5 mg/kg adenosine intraperitoneally. Inflammatory intensity was evaluated clinically by knee swelling measurement, histology, the total white blood cell (WBC) count, and serum tumor necrosis factor-alpha (TNF-a) levels served as markers of systemic inflammatory reaction. As observed, only the mice that received the higher dose of 0.5 mg/kg adenosine developed a significantly milder arthritis. A 23.9% reduction (P o 0.004) of the mean knee diameter swelling was noted. The histological inflammatory parameters and WBC count in the 0.5 mg/kg adenosine-treated mice were also decreased (6,555 7 510/mm 3 vs. 9,250 7 530 WBC/mm 3 in the untreated mice, P 4 0.006; 9,188 7 588 WBC/mm 3 in the 0.25 mg/kg adenosine-treated group). Serum TNF-a levels were significantly reduced (78.1 pg/ml in the 0.5 mg/kg adenosine-treated group vs. 124.3 pg/ml, in the control group, P o 0.004). The data indicate a remarkable clinical beneficial effect, as well as a local and systemic anti-inflammatory response that was noted on administration of 0.5 mg/kg adenosine every alternate day to mice with inflammatory arthritis. Drug Dev. Res. 57:182-186, 2002.

There were 55 Israeli patients with Behcet's disease (BD) included in a study conducted to determine the correlation between HLA-B5 and clinical manifestations and severity of the disease. The systemic manifestations of BD were analyzed in relation to HLA typing, and a systemic severity score for BD was calculated according to potential morbidity and mortality associated with various clinical features. Of the 55 patients, 42 (76.4%) were sephardic Jews, 2 (3.6%) were ashkenazi Jews, and 11 (20.0%) were Israeli Arabs. There were 39 (70.9%) HLA-B5 positive patients; they had a significantly higher incidence of thrombophlebitis and a lower rate of erythema nodosum. The HLA-B5-positive patients were significantly older at disease onset, and their severity score tended to be higher, although not statistically significant.The results of our study imply that HLA-B5 in Israeli patients is associated with specific clinical features, especially more vascular disease, and may be associated with a more severe course of BD. This is of general interest because American and North European patients also have less HLA-B5 and less severe disease. (J Clin Rheumatol 1999;5:137-140).

Objective. To study the clinical spectrum of Behcet's disease (BD) in childhood, in comparison to adult-onset disease. Methods. Nineteen children, who fulfilled disease criteria up to the age of 16 yr, were studied. The results were compared to those of 34 adult patients with BD. An activity index and severity score were calculated for both study groups. Results. The mean age of disease onset was 6.9± 3.9 yr, similar ages of onset were found in males and females. The clinical spectrum of childhood BD resembled that of adult disease; however, the prevalence of certain manifestations was diVerent between children and adults. Children with BD had significantly less genital ulcers, less vascular thromboses and more non- specific gastrointestinal symptoms, as well as central nervous system involvement and arthralgia. A relatively high prevalence of uveitis was found in childhood BD. The activity index and severity score were significantly lower in children than in adults. Conclusion. Our results point to a similar systemic expression of BD in children and adults; however, the disease seems to run a less severe course in children.

Patients with systemic lupus erythematosus (SLE) were evaluated using a telephone questionnaire on the activity of various disease manifestations during the seasons of the past year. The results were compared to those of patients with Behcet's disease (BD), using the same questionnaires, and analyzed in relation to the mean temperature, humidity, barometric pressure, and ultraviolet radiation (UVR) in the patient's location, obtained from the official Israeli Meteorological Service. It was found that SLE patients had a tendency towards winter worsening of clinical manifestations, shown as increased incidence of joint pains, weakness, fatigue, Raynaud's phenomenon, and rash, as well as increased number of hospital admissions, sick leaves, and need to raise the dose of medications. The symptoms of patients with BD were not correlated to seasons of the year, except for increased joint pains in autumn and spring. We suggest that UVR accumulation might cause exacerbations in SLE patients several months after prolonged exposure to sunlight in the summer.

An extensive study looking for signs of inflammatory arthritis in the paintings of the impressionists was performed at the Orsay Museum in Paris, France. Of the 435 paintings reviewed, 3 works by different painters were found to show signs of inflammatory arthritis of the hands. We suspect that the importance of the arthritis in the models' lives led the painters to emphasize this condition in their paintings.

The human lymphocyte antigen (HLA) molecule B*5101 is a functioning receptor of the immune system and is generally accepted as a genetic marker for Behçet disease (BD), a multi-organ, chronic inflammatory disorder. The role of the HLA-B*5101 in the pathogenesis of BD is elusive. The assumption that HLA-B*5101 has an active role in BD is suggestive, but no antigen has yet been identified.To evaluate the potential binding capacity of various antigens to the HLA-B*5101 molecule.Using bioinformatics programs, we studied the binding capacity of HLA-B*5101 and its corresponding rat molecule RT.A1 to the following antigens: heatshock protein-60 (HSP60), major histocompatibility complex class I chain-related gene A (MICA), retinal S-antigen (S-Ag), HLA-B27 molecule and its peptide (PD) and tropomyosin (TPM), all of which serve as antigens in animal models corresponding to BD.In each protein including the B*5101 molecule itself, the computerized programs revealed several short sequences with potential high binding capacity to HLA-B*5101 with the exception of B-27PD. The rat MHC RT1. Al. had no binding capacity to S-Ag.The evaluated proteins have the potential to bind to and to serve as potential antigens to the HLA-B*5101 and the rat MHC RT1.Al. molecules. The pathogenicity of these suggested short peptides should be evaluated in animal models of BD.

Objective: Previous studies suggest that selective serotonin reuptake inhibitors (SSRIs) modulate immune system functionality. SSRIs are the preferred treatment for major depressive disorder (MDD). A high rate of MDD is observed in rheumatoid arthritis (RA) patients. The aim of this study was to evaluate immunological effects of SSRIs in a rat model of RA. Methods: Adjuvant arthritis was induced in 8-week-old Lewis rats; in the first set of experiments following the induction, 15.3 or 30.6 mg/kg of sertraline was daily injected into the ankle joint of the left rear leg. Clinical disease activity was evaluated and the findings compared with the 3 untreated legs and with control groups given methotrexate (MTX) or vehicle only at the same site. In a second set of experiments, the effect of 5, 25 and 50 mg/kg daily oral sertraline was evaluated in the same rat model. Splenocyte viability and inflammatory mediators were evaluated. Results: The sertraline-treated rats showed a significant reduction in clinical arthritis compared to controls, at all doses given, accompanied by a significant increase in interleukin 10 and a decrease in tumor necrosis factor-α levels and cycloxygenase-2 production, without lymphotoxicity. There was no significant difference from MTX, the first-line treatment for RA patients. Oral sertraline had a significant anti-inflammatory effect at all doses. There was no treatment × time effect. Conclusion: The beneficial effects of sertraline in this rat model of arthritis have clinical implications for its use in humans. Large-scale clinical efficacy trials are needed.

Low levels of oestrogen, FSH and LH in serum have been reported in patients with gout. The mechanism by which sex hormones affect the development of gout is unknown, but some investigators believe that it is related to the influence of oestrogens on serum uric acid levels. We studied the relationship between serum uric acid and 17 beta oestradiol (ES) levels in asymptomatic hyperuricaemic (ASH) men in order to test the hypothesis that low ES levels are associated with hyperuricaemia. Thirty-eight men with asymptomatic hyperuricaemia (ASH) were selected from a population of healthy individuals undergoing periodical multiphasic health examinations. After adjusting for the differences in albumin levels between the two groups, no significant difference in serum ES level was found. The serum testosterone levels were similar in both groups. These findings suggest that there is no difference in the sex hormone profiles between asymptomatic hyperuricaemic and normouricaemic men.

OBJECTIVES--To assess the expression of systemic lupus erythematosus (SLE) in Jewish Israeli patients according to ethnic origin. METHODS--Eighty four patients with SLE were divided into groups according to origin and compared for history, physical examination, and laboratory variables. RESULTS--Patients of Sephardic origin had more serious disease manifestations than Ashkenazi patients in 60 of the 76 variables examined. They had significantly worse muscle pain, alopecia, and cutaneous vasculitis, higher antibodies to DNA and erythrocyte sedimentation rate, and significantly lower complement and leucocytes. Sephardic patients were divided into subgroups according to country: Mediterranean area, Iran-Iraq-India, and Yemen. All three subgroups had more serious disease manifestations than the Ashkenazi group, and the Yemenite patients had the most serious manifestations among the Sephardic subgroups. The Sephardic patients had a significantly lower education level, but only origin, and not education level or age, was significantly related to disease manifestations on multivariate analysis. CONCLUSION--More serious manifestations of SLE are found among Jewish patients of Sephardic origin, but these are not related to level of education or age.

Animal models for Behcet’s disease (BD) can be divided according to the proposed etiological paradigms. These include environmental pollution and infectious (bacterial and viral) models, as well as various autoimmune and transgenic animal models. The environmental pollution model, though resembles the multisystem symptoms of BD, has limitations to become utilized as a model for the disease since it is difficult to produce and the onset of symptoms appears erratically in a wide time range. The Streptococcal models have similarity only to the eye involvement in BD. This model is simple to induce with high rate of homogeneity. The HSV model has multisystem manifestations resembling BD; it has a moderate reproducibility. The autoimmune model utilizing S-Ag is a monosymptomatic model of BD-like uveitis. This model is easy to induce, and extensive studies elucidated some of the immunological characteristics of BD including the paradigm of anti-HLA autoimmunity. The α-tropomyosin model shares some clinical features of BD. This model has a potential to become a useful autoimmune model for BD. The only published trial to establish a transgenic model for BD did not show any significant similarity to the human disease except hyper-responsiveness of neutrophils.

A patient with acute onset of purpuric rash and arthritis is presented. He was taking acetaminophen 10 days before the onset of the symptoms. The cutaneous lesions were caused by leukocytoclastic vasculitis on histologic examination. Rechallenge with the drug was followed by the appearance of new similar lesions.

To summarize recent scientific developments in the epidemiology, genetics, pathogenesis and treatment of Behçet's disease.Important genetic and immunologic studies were performed. Tumor necrosis factor-alpha-1031C allele was associated with disease susceptibility. Polymorphisms in interleukin-10, IL-8 and CD28 genes were also associated with Behçet's disease. Association with endothelial nitric oxide synthase gene polymorphism was confirmed but was ethnic related. Significant T helper type 1 immune reaction was reconfirmed in recent studies, especially during active phases, but T helper type 2 reaction may also play a role. Interleukin-12B heterozygosity is associated with Behçet's disease susceptibility and plays an important role in mediating T helper type 1 antistreptococcal immune response. Selenium binding protein may be a target antigen in Behçet's uveitis. Pathergy reaction is most frequently positive in the forearm; multiple needle pricks increase positive rate. Experience with anti-tumour necrosis factor therapy for various manifestations is increasing. Cyclosporin A treatment may be associated with new onset of neuro-Behçet. There is a high prevalence of headaches with moderate or severe disability. Cardiac manifestations include left ventricular dysfunction and coronary flow abnormalities. Anti-Saccharomyces cerevisiae antibodies may be especially common in intestinal Behçet's disease and are also increased in healthy relatives of patients.Considerable progress has been made, particularly in understanding the immunologic and genetic basis of the disease. The importance of novel serological markers and autoantigens merits further investigations.

CF101, an A3 adenosine receptor (A3AR) agonist, is a small orally bioavailable molecule known to suppress in vitro the production of tumor necrosis factor-alpha (TNF-alpha). We evaluated its therapeutic potential and antiinflammatory effects in 3 murine models of adjuvant induced arthritis (AIA).The antiinflammatory effect of CF101 was examined in rat AIA, in mouse collagen induced arthritis, and in tropomyosin induced arthritis. The clinical effect of another A3AR agonist, Cl-IB-MECA, was examined in rat AIA. The effect of low dose (10 or 100 mg/kg/day) A3AR agonists administered orally once daily on arthritis severity was assessed clinically and histologically. The effect of CF101 on the protein expression level of TNF-alpha in the synovial tissue, draining lymph nodes, and spleen cells was determined by Western blot.CF101 and Cl-IB-MECA markedly ameliorated the clinical and histological features of arthritis in the 3 models when administered orally at a low dose of 10 mg/kg body weight in the 3 autoimmune arthritis models. The lower dose of 10 mg/kg of either CF101 or Cl-IB-MECA had better antiinflammatory effect than the higher 100 mg/kg dose. Decreased expression of TNF-alpha was noted in protein extracts of synovia, draining lymph nodes, and spleen tissues.The results provide evidence that A3AR agonists exert significant antirheumatic effects in different autoimmune arthritis models by suppression of TNF-alpha production. The beneficial activity of the drugs at the low dose demonstrates that the effect is A3AR mediated.

Objective To determine the effect of treatment with C48, the recombinant cytokine-like domain of the novel human placental immunomodulator ferritin (PLIF) immunoregulator, on zymosan-induced arthritis (ZIA) in mice and on adjuvant-induced arthritis (AIA) in rats. Methods The in vitro effect of PLIF/C48 was tested in mixed lymphocyte cultures (MLCs) of allogeneic mouse splenocytes. Arthritis was induced by intraarticular injection of zymosan into naive mice and by subcutaneous injection of Mycobacterium tuberculosis into rats. C48 was injected intraperitoneally daily from day 3 to day 9 or from day 7 to day 13 after induction of synovitis by zymosan, and every other day from day 2 to day 14 after induction of AIA. Swelling of the joints and histologic features of the synovium were assessed. Th1 and Th2 cytokines were quantified by enzyme-linked immunosorbent assay. Results Both PLIF and C48 significantly inhibited the in vitro immunoreactivity of mouse splenocytes in MLCs. Treatment of ZIA mice and AIA rats with C48 effectively reduced joint swelling. C48 treatment reduced synovial lining thickening, numbers of mononuclear cells and histiocytes, as well as cartilage destruction and bone erosions. In vitro, activated splenocytes from C48-treated ZIA and AIA animals produced significantly higher levels of interleukin-10 (IL-10). In animals with ZIA, this was accompanied by lower levels of tumor necrosis factor and IL-2. Conclusion Human PLIF and C48 were shown to exert cross-species immunosuppressive activity in vitro. The in vivo suppression of articular inflammation in the experimental models of ZIA and AIA was the result of treatment with the antiinflammatory human C48. These results suggest that treatment with C48 may offer an effective immunotherapeutic means of controlling inflammatory polyarthritis.

82 patients were retrospectively evaluated for the effects of maximal and minimal temperatures, barometric pressure, wet and dry temperatures and heat stress on the five consecutive days preceding an acute gouty attack. Maximal temperature on day four preceding the attack was higher than the monthly mean [p < 0.01], the fifth day's lower than the monthly mean minimal temperature [p < 0.05], and the mean barometric pressure of the fifth day before the attack higher then the monthly mean [p < 0.02], On day four before the acute gouty arthritic attack heat stress was significantly higher than the mean monthly heat stress [p < 0.03]. The same findings were noted between the difference of the fifth night wet and fourth night dry temperatures, which were higher than those on the day of the attack [p < 0.05 and p < 0.03 respectively]. These weather changes were not specific to a certain month. Weather changes which occur four to five days before an acute gouty attack may play a significant role in precipitating ...

Systemic lupus erythematosus-associated irreversible organ/system damage was previously associated with various clinical and demographic features. We analysed the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI) in a cohort of 151 Israeli patients followed for a mean (§ s.d.) period of 45.7§ 37.4 months. Mean score of SLICC/ACR DI at the first and last encounters were 0.17§ 64 and 1.64§ 2.1, respectively (P < 0.0001). Multiple logistic regression analyses disclosed a statistically significant positive correlation with corticosteroid and cyclophosphamide therapy. Hydroxychloroquine therapy was significantly associated with lower SLICC/ACR DI. Although the size of our study group did not allow us to find specific organs/systems which were associated with the protective effect of hydroxychloroquine, we suggest this is due to the antiatherogenic effects attributed to antimalarial therapy in SLE.

Objective: To evaluate the prevalence of Behcet9s disease (BD) in an Israeli Arab town (Taibe). Methods: Questionnaires about the occurrence and prevalence of aphthous ulcers were distributed randomly to the parents of children attending a paediatric centre in Taibe. The parents were asked whether they or any of their children aged between 10 and 20 years had recurrent aphthous stomatitis. Any who had had more than four aphthous episodes (each episode lasting more than seven days) during the previous year were invited for an extensive interview and examination by a rheumatologist or a paediatrician. Results: A total of 4876 subjects were included in this survey, of whom six (one male, five female) were diagnosed as having BD. Of these six, two were siblings (a brother and a sister). Five had skin lesions, four had visual involvement, and all had genital ulcers and joint symptoms; one in two patients had a positive pathergy test. Five of the six carried HLA-B5 antigens. The results showed a prevalence of 12/10 000 in Taibe. Conclusion: The prevalence of BD found in our survey is high and concurs with that found in other Mediterranean and Asian countries.

Behçet's syndrome is a multi-system inflammatory disease affecting mainly the oral and urogenital mucosa and the uveal tract. The etiology and pathogenesis of Behçet's syndrome are unknown, but autoimmune mechanisms are implicated. We initiated this work to identify self-antigens targeted by patients with Behçet's syndrome. We used patient sera to immuno-blot tissue lysates, and we found that some patients manifest antibodies to a 37-kDa band. The 37-kDa band was detected in extracts of skin, tongue, vagina, muscle and heart but not in brain, kidney, lung, liver, intestine and thymus. In-gel digestion and mass spectrometry revealed the band to be alpha-tropomyosin. Autoimmunity to alpha-tropomyosin can be pathogenic; immunized Lewis rats developed lesions in the uveal tract and skin, with features of Behçet's disease.

Significant fatigue was observed in 63/83 (76%) SLE patients. Patients with fatigue had significantly lower lymphocyte counts (1090 +/- 60 vs 1675 +/- 205 cells/mm3 P = 0.003), and higher ratings for headache, nervousness and musculoskeletal symptoms and signs. These disease parameters also correlate significantly with the magnitude of fatigue. Fatigue correlated with disease activity index (r = 0.49 P < 0.001).

Saliva coating all oral surfaces has a buffering capacity that neutralizes bacterial and cariogenic acids. The aim of our study was to determine the surface pH in different regions of the oral cavity in healthy volunteers and in patients with diseases affecting the oral mucosa. Oral pH was measured with a flat glass electrode on the anterior third of the ventral surface of the tongue, middle hard palate, buccal mucosa and inner lips in 32 healthy volunteers, 12 patients with Behcet's disease, 23 patients with oral lichen planus, and 11 patients with burning mouth syndrome. The present study showed that there was an uneven distribution of oral surface pH. The palate had a higher pH than most other sites in all groups, and in patients with lichen planus, the palate pH was higher than that in healthy controls. Those with dentures had lower pH values in the hard palate than dentate patients. The relatively high pH in the palate region in all patient groups as well as healthy volunteers needs to be further studied to clarify its mechanisms and clinical relevance.

Background The prevalence of Behcet’s disease (BD) varies in different parts of the world. Objectives To evaluate the prevalence of BD in an Israeli Arab town (Taibe). Methods Questionnaires about the occurrence and frequency of aphthous ulcers were distributed randomly to the parents of children attending a Paediatric Clinic in Taibe. The parents were asked whether they or any of their children aged over 10 years suffered from recurrent aphthous stomatitis (RAS), and if so, any who had had more than four episodes during the previous year where each episode had lasted for more than 7 days were invited to come for an extensive interview and examination by a rheumatologist or a paediatrician. Results Overall, six individuals (one male and five females) were diagnosed as suffering from BD. All of these, two of whom were siblings (a brother and a sister) had RAS, genital ulcers and joint manifestations. Five had skin and four had visual involvement, and one out of two had a positive pathergy test. Five of the six carried HLA-B5 antigens. This gave a prevalence in Taibe of 12/10,000. Conclusion The prevalence of BD found in our survey is high and concurs with that found in other Mediterranean and Asian countries where a high prevalence has also been noted.

Objectives: The angiotensin-converting enzyme (ACE) gene polymorphism has been associated with worse outcome in various chronic glomerular disorders and in hypertension. Because nephritis and vascular morbidity are prominent determinants of outcome in systemic lupus erythematosus (SLE), we studied the distribution and prognostic effect the ACE genotype might have on the outcome of SLE. Methods: Fifty-six consecutive Israeli SLE patients and 48 (sex and ethnic origin matched) healthy individuals were evaluated for the ACE genotype by a polymerase chain reaction—based assay. The clinical and laboratory parameters of the patients as well as the SLE disease activity index (SLEDAI) and the presence of hypertension, diabetes mellitus, ischemic heart disease, congestive heart failure, and stroke were correlated with the ACE genotype. Results: The distribution of the ACE genotype D/D, D/I, and I/I in the lupus group was 59%, 36%, and 5%, respectively, similar to the distribution in the control group (54%, 31%, and 15%, respectively). We failed to find any significant association between the ACE genotype and disease manifestations, SLEDAI, renal function, or cardiovascular and cerebrovascular morbidity. The clinical and laboratory parameters associated with renal outcome and vascular morbidity in our cohort are described. Conclusions: No difference was found between the distribution of the ACE genotype in lupus patients and the general population in Israel. Renal function as well as cardiovascular and cerebrovascular morbidity among Israeli patients with SLE are disease-related and independent of the ACE gene polymorphism. Semin Arthritis Rheum 30:132-137. Copyright © 2000 by W.B. Saunders Company

A 22 year old woman presented with lupus nephritis, hypertension, and intractable nephrotic syndrome. Albumin and furosemide given intravenously was ineffective. Captopril administered in a daily dose of 62.5 mg was associated with a reduction in proteinuria from 28 g/24 hours to 11.5 g/24 hours over 10 weeks, resulting in a weight reduction of 16 kg. This was achieved with relative preservation of renal function. Captopril should be considered in the treatment of intractable proteinuria in patients with lupus nephritis, or when cytotoxic drugs are refused, because of its efficacy and relative safety. Captopril should, however, be used as an adjunct and not as a substitute for standard treatment.

Lymphadenopathy (LAP) is a frequent sign in systemic lupus erythematosus (SLE). Yet, data concerning its relation to the various disease manifestations are scarce or absent. LAP was present in 23/90 (26%) SLE patients. Patients with LAP had significantly more constitutional symptoms of fatigue, fever and weight loss, more cutaneous symptoms and signs, a higher rate of hepatomegaly and splenomegaly, increased anti-dsDNA antibodies and decreased complement levels. Disease activity index was higher among patients with LAP, as was the intake of steroids and antimalaria medications. There was no difference in renal or central nervous system (CNS) involvement between patients with LAP and those without LAP.

Objective. To examine the potential immunologic mechanism and involvement of antiphos pholipid antibodies in the pathogenesis of heart valve lesions in patients with the antiphos pholipid syndrome (APS).Methods. Immunoperoxidase and immunofluorescence staining methods were used to evaluate 13 heart valve specimens derived from eight patients with the APS, either primary or secondary to systemic lupus erythematosus. Primary antibodies to human immuno globulins, complement components, serum albumin and a monoclonal anti-idiotypic anti body to human anticardiolipin antibodies (aCL) were employed. Various tissue specimens from a patient with the APS as well as deformed and normal valves from subjects without the APS were used as controls.Results. Linear subendothelial deposition consisting of immunoglobulins with complement components but not of a non-specific serum protein was found in deformed valves from patients with the APS. None of the control valves or tissues disclosed similar deposition. The same pattern and location of staining was obtained by the anti-idiotypic antibody to aCL. A significant amount of IgG immunoglobulins that bound to cardiolipin was eluted from a valve of a patient with secondary APS.Conclusion. Deposits of immunoglobulins including aCL, and of complement components, are common in affected valves of patients with primary and secondary APS. Such deposits may be involved in the pathogenesis of valvular lesions.

Minocycline, a semi-synthetic tetracycline, was injected into one hind joint of twenty-two rabbits with zymosan-induced arthritis, while the contralateral joint served as a control. A local inflammatory reaction was observed a few days after the zymosan injection. Most clinical parameters such as knee diameter, systemic temperature, sedimentation rate and blood cell count did not change throughout the experiment both in control and minocycline treated rabbits. However, the zymosan platelet counts rose from 3.4x10(5)/microL to 5x10(5)/microL, as well as the level of serum fibrinogen (from 99 mg% to 370 mg%). Microscopically, a perivascular infiltrate consisting of lymphocytes and polymorphonuclear cells was seen. Lymphoid follicles as well as plasma cells epitheloid and giant cells were also observed. A mild tendency to fibrosis and lesser inflammatory reaction in the minocycline treated knees was noted. Our data suggest that intraarticular minocycline treatment did not alleviate the course of the rheumatoid-like inflammatory reaction of the knee joint.

Serum triglyceride levels are significantly higher and serum high-density lipoprotein cholesterol levels are lower in patients with gout compared with healthy individuals. Whereas increased serum triglyceride levels exist intrinsically in gout, serum uric acid concentration correlates inversely with insulin sensitivity and positively with serum triglycerides. Interaction of monosodium urate crystals with granulocyte-macrophage colony-stimulating factor and with tumor necrosis factor-activated neutrophils favored the production of interleukin-1 over that of interleukin-1-Ra, resulting in a proinflammatory imbalance. Interaction of the crystals with iron or tyrosine kinase may modify their inflammatory response and can be an important modulating mechanism in gouty arthritis. E-selectin is a specific marker for synovial fluid soluble endothelial activity and is increased in the synovial fluid of patients with gouty arthritis, as well as in that of patients with other inflammatory arthritides. Similarly, E-selectin was found to be high in joints with monosodium urate crystal-induced synovitis. In addition, synovial fluid levels of interleukin-8 were found to be high in gout, rheumatoid arthritis, and osteoarthritis.

In order to investigate the sub-typing of the B5 antigen in Israeli (Jewish and Arabic) patients with Behcet's disease (BD) allele-specific genotyping of B51 and B52 alleles was performed in Israeli BD patients and healthy controls. Among the HLA-B51-positive BD patients, B*5101 was found to be the predominant allele, identified in 62% of all BD patients and 78% of Jewish BD patients. HLA-B*5101 was also the predominant allele in HLA-B51-positive healthy controls. HLA-B*5108 and B*5104 alleles were identified in 23% and 15% of B51-positive BD patients, respectively. The HLA-B*5201 allele was identified in all HLA-B52-positive patients and controls. Our study suggests that both HLA-B*5101 and HLA-B*5201 are the dominant alleles of HLA-B5 in Israeli BD patients.

Rash is a common cutaneous sign in patients with systemic lupus erythematosus (SLE) but no data regarding its prevalence or relation to disease manifestations are known, possibly due to the fact that it is a common but non-specific sign. Rash was present in 48/81 (59%) patients with SLE. Patients with rash had more cutaneous symptoms and signs, lymphadenopathy, increased levels of antibodies to double stranded DNA and decreased complement levels. They were also receiving a higher dose of prednisone. There was no difference between patients with and without rash with respect to renal or central nervous system disease. Rash did not correlate with the disease activity index and clinical parameters of disease exacerbation.

The effect of local deep microwave hyperthermia (LDMWH) on normal and Zymosan-induced arthritis has been evaluated in 12 rabbits (24 joints). LDMWH, four treatments to each joint (twice weekly for a period of 2 wk), was generated by an antenna operating at 915 MHz for 60 min, reaching an intraarticular temperature of 42.5 +/- 0.5 degrees C. A surface cooling system was used with the microwave apparatus. Two weeks after the last treatment, all animals were sacrificed. The application of LDMWH on normal joints induced a limited proliferation of the synovial lining cells with a minimal perivascular infiltration of mononuclear and neutrophil cells. However, no histologic damage to the skin, muscles, bone, cartilage or bone marrow adjacent to the heated joints could be noted. Induction of Zymosan arthritis (2 wk before LDMWH) was characterized by pannus formation and granulomatous reaction accompanied by fibrinoid deposits and disseminated necrotic foci in the synovial intima. The LDMWH treatment on the examined arthritic joints brought about a reduction in the degree of granulomatous reaction concomitant with the appearance of some fibrocytes and fine collagen fibrils. These findings suggest that LDMWH can be safely applied, even repeatedly, without morphologic evidence of damage to any normal mesenchymal tissue. Moreover, it reduces the inflammatory process in experimentally induced synovitis.

purpose: The purpose of this study was to assay serum cobalamin levels in patients with systemic lupus erythematosus (SLE) as there are few case reports on the association of pernicious anemia and SLE. patients and methods: Serum cobalamin levels were assayed in 43 female SLE patients by a radio-dilution assay using purified intrinsic factor. results: Cobalamin levels were found to be significantly lower in the SLE group compared with a normal control group, eight of whom (18.6%) had serum cobalamin levels equal to or lower than 180 pg/mL (mean: 129.25 ± 40.05 pg/mL). None of the SLE patients had been found to have pernicious anemia. The transcobalamin II level and unsaturated vitamin B 12 binding capacity, but not the cobalamin level, were positively correlated with SLE activity. conclusions: Our results may indicate a subtle cobalamin deficiency in SLE patients without pernicious anemia.

Objectives To investigate the incidence and clinical features of recurrent aphthous stomatitis (RAS) among Israeli Arab adolescents and to determine the HLA typing profile in affected subjects. Study Design Cross-sectional study. Setting Junior high school in the largest Arab town in Israel. Participants Four hundred seventy-seven Israeli Arab junior high school students filled out a questionnaire. Students who reported more than 4 episodes of RAS during the previous year were interviewed by telephone. Those whose responses were confirmed were invited to the clinic. Of these, 22 were chosen at random for HLA typing. Findings were compared with those in 117 healthy Israeli Arabs who were candidate donors of bone marrow to patients at the Institute of Hematology–Oncology, Schneider Children's Medical Center of Israel, Petah Tiqva. Results Recurrent aphthous stomatitis was confirmed in 80 subjects (16.7%). Of the 22 patients who underwent HLA typing, 7 (31.4%) had HLA-B52 antigens and 8 (36.4%) had HLA-B44 antigens; corresponding figures for the control group were 10 subjects (8.5%) ( P = .007) and 9 subjects (7.7%) ( P = .001), respectively. Conclusions There is a close association of HLA-B52 and HLA-B44 in Israeli Arab youths with RAS. Long-term follow-up is needed to determine the relationship between RAS and Behcet disease.