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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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

In order to assess the value of the leukergy test in which leukocytes aggregate in citrated whole blood, we examined 65 patients with various rheumatic conditions. In addition, plasma samples from 40 patients were examined for neutrophil aggregation activity in vitro. Results of the leukergy test were found to be in very good correlation with disease activity (P = 0.0001), whereas no increased neutrophil aggregation activity was found in the 40 plasma samples examined. The value of the leukergy test in assessing patients with rheumatic disease and its theoretical etiopathogenic role in these diseases are discussed.

Previous work has shown that leucocyte adhesiveness/aggregation (LAA), as measured by the leukergy test, correlates well with disease severity in rheumatic patients. As LAA is probably a manifestation of the acute phase reaction various components of the acute phase reaction were measured in order to identify the best marker of disease activity. In addition to LAA, the following variables were measured in 79 patients with various rheumatic diseases and in 10 controls: white blood cell and platelet counts, erythrocyte sedimentation rate, haptoglobin, fibrinogen, C reactive protein, albumin, globulin, caeruloplasmin, alpha 1, alpha 2, beta, and gamma globulin, and haemoglobin concentrations. Patients were graded according to the state of their disease as mild, moderate, or severe. The extent of leucocyte adhesiveness/aggregation in peripheral blood proved to be the best laboratory variable for the grading of disease activity. Correct grading was obtained in 63% of the patients by means of the LAA, compared with 48% with C reactive protein, 41% with caeruloplasmin, 40% with haptoglobin, and 32% with haemoglobin. It is suggested that LAA of the peripheral blood during inflammation may be used as a reliable marker of disease severity.

A 16-year-old patient with Behcet's syndrome had massive hemoptysis due to a ruptured aneurysm of a segmental artery of the left lung. Emergency left lower lobectomy was performed. The patient is well 12 months after operation. There have been no further episodes of hemoptysis.

An elderly patient with chronic myelomonocytic leukaemia developed severe bone pains and acute gonarthritis. Intravenously administered cytosine arabinoside brought dramatic relief of the bone pains and led to a rapid subsidence of the arthritis, without achieving haematological remission.

In previous studies we have been able to demonstrate crystals in asymptomatic 1st metatarsophalangeal(MTP)joints never clinically involved in 66% of gouty patients. In small group of subjects with asymptomatic hyperuricemia(AHU)crystals could not be identified by using this technique. Recent studies have displayed the presence of MSU crystals in asymptomatic hyperuricemic individuals without an history of gout. Since it is a controversial issue whether subjects with AHU are susceptable to develop gout than those with normouricemia, we extended the study. Aspiration of asymptomatic 1st MTP joint was attempted in 31 subjects with AHU with no history of gout or pseudogout. Of them 12 had psoriasis, 6 with chronic renal failure(CRF)with 3.2 yrs mean duration of hyperuricemia,and 11 subjects had various types of associated diseases. Two subjects had AHU with no other associated diseases.Serum uric acid levels were 8.0-14.5 mg/dl, mean 9.8 mg/dl. Serum creatinine levels were 0.8-7.5 mg/dl, mean 1.7 mg/dl. Negatively birefringent rod crystals typical of MSU was found only in the aspirated fluid of one patient who suffered from psoriasis. Our finding that no patient with CRF had positive MSU crystals in the aspirates is in contrast to previously published reports of about 30% prevalence of crystalline deposits in these patients' toe. We confirm previous studies in which crystals may only rarely be found in hyperuricemic patients who have never had symptoms of arthritis.