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Biomedical subjects

S Padeh

Publications and source records attributed to S Padeh.

28 records · Page 2Linked to original sources

[Systemic lupus erythematosus in children in Israel].

Systemic lupus erythematosus (SLE) is a rare disease in children that might possibly be modulated by genetic and environmental factors. In order to delineate the characteristic features of SLE among Israeli children, we reviewed the medical records of 38 cases from 8 pediatric rheumatology clinics. All fulfilled the 1982 American Rheumatism Association revised criteria for SLE. The illness became apparent at the age of 16 years or younger and the mean age of onset was 11.9 +/- 2.4 y (range 7-16) and the mean duration of follow-up 4.0 +/- 4.8 y (range 0.5-15). The female to male ratio was 2.8:1; 28 were Jewish and 10 Arabs. Systemic complaints, such as fever, malaise and weight loss, were noted in 90%, malar rash in 65%, and other skin manifestations in 40%. Arthritis was noted in 57% and additional musculoskeletal complaints in 70%; 90% had hematological abnormalities. Major organ system involvement included: renal disease in 50% pulmonary involvement 28% and CNS involvement 28%. 2 patients are currently on renal dialysis and 1 died from hypertensive crisis. We conclude that the features of SLE in children in Israel are not influenced by ethnic or geographic factors, and are similar to those reported worldwide.

Adolescent↗

High synovial immunoglobulin E levels in eosinophilic synovitis.

Eosinophilic synovitis occurred in a 7-year-old boy. Synovial fluid leukocytes were mostly eosinophils; the peripheral blood showed only mild eosinophilia. The level of eosinophil-derived neurotoxin in the synovial fluid was higher than that in the serum, suggesting intraarticular eosinophil degranulation. The IgE level was also elevated in the synovial fluid (3854 ng/ml) but normal in the serum (408 ng/ml), suggesting a localized immediate hypersensitivity immune response.

Child↗

ATP-induced activation of human B lymphocytes via P2-purinoceptors.

ATP-specific P2-purinoceptors expressed on various cell types have been shown to trigger cell activation via a phospholipase C pathway. In the present study, we provide evidence that P2-purinoceptors are expressed on B lymphocytes but not on T lymphocytes. ATP at concentrations of 10 to 100 microM triggered a dose-dependent increase in inositol 1,4,5-trisphosphate (IP3) levels as well as total inositol phosphate in human B lymphocytes. As expected from the changes in IP3, incubation of B cells with increasing concentrations of ATP lead to a dose-dependent increase in cytosolic free Ca+2 ([Ca+2]i). Extracellular ATP also induced increases in the levels of c-fos and c-myc mRNA. Because no responses were elicited by other nucleotides, the increase in IP3 production, the rise in [Ca+2]i levels, and the enhanced expression of c-fos and c-myc mRNA seem to be mediated by P2-purinoceptors. These responses were exclusive to B lymphocytes, in that ATP had no effect on IP3, [Ca+2]i, or oncogene expression in T cells. The results show that binding of extracellular ATP to P2-purinoceptors on quiescent B cells leads to the activation of genes associated with cell activation. This appears to be mediated via the phospholipase C signal transduction pathway.

Adenosine Triphosphatases↗

Primary pulmonary hypertension in a patient with systemic-onset juvenile arthritis.

We describe a 16-year-old girl with systemic-onset juvenile arthritis who presented with pulmonary hypertension, without evidence of pleural or parenchymal involvement of the lung, pulmonary vasculitis, or immune deposition in the pulmonary vasculature. Pleuropulmonary involvement occurs occasionally in juvenile arthritis, but primary pulmonary hypertension has not, to our knowledge, been previously reported. Histocompatibility typing showed positivity for HLA-DR3 and DRw52, both of which are associated with idiopathic pulmonary hypertension in children, and with pulmonary hypertension among patients with systemic sclerosis. Treatment with cyclosporine and corticosteroids resulted in a marked improvement in the clinical findings and pulmonary function in our patient.

Adolescent↗

Activation of phospholipase C in human B cells is dependent on tyrosine phosphorylation.

Cross-linking of the surface antigen receptor on B lymphocytes has been demonstrated to lead to activation of phospholipase C (PLC) with subsequent increases in production of inositol phosphates and diacylglycerol. In turn, these second messengers increase cytosolic free calcium [( Ca2+]i) and activate the serine threonine phosphotransferase protein kinase C (PKC). These processes are thought to play a major role in B cell activation and proliferation. However, the mechanism linking the B lymphocyte antigen receptor to phospholipase C remains to be identified. We demonstrate herein that activation of the antigen receptor on human lymphocytes, in addition to activation of PLC, increases tyrosine phosphorylation of specific substrates. Tyrphostins, a new class of tyrosine kinase inhibitors which compete for substrate binding site of specific tyrosine kinases have recently been synthesized. Preincubation of B lymphocytes with two different tyrphostins blocked anti-IgM-induced proliferation, oncogene expression, tyrosine phosphorylation, increases in [Ca2+]i, and production of inositol phosphates. The same inhibitors were without effect on B cell proliferation induced by phorbol esters and cation ionophores which directly activate PKC and increase [Ca2+]i thus bypassing PLC. These findings strongly indicate that tyrphostins do not exhibit significant nonspecific toxicity and suggest that they act proximal to PLC. The ability of the tyrphostins to block increases in [Ca2+]i and inositol phosphate production, after activation of the B cell antigen receptor, indicates that a tyrosine kinase acts as an essential link between the B cell antigen receptor and PLC.

B-Lymphocytes↗

Activation of human monocytes via their sIgA receptors.

We have studied the interaction of secretory immunoglobulin A (sIgA) derived from human breast milk with human monocytes. The presence of specific sIgA receptors on the monocyte membrane was confirmed by dose-dependent inhibition of E-sIgA rosette formation and by the binding of iodinated sIgA to monocyte monolayers. Binding was dependent on both the number of monocytes, as well as the amount of [125I]sIgA, and could be inhibited by unlabelled sIgA. Incubation of monocyte monolayers in the presence of increasing concentrations of secretory IgA and F(ab')2 anti-IgA resulted in a dose-dependent increase of the oxidative burst, as measured by H2O2 production. Neither sIgA or anti-IgA alone, nor incubation of IgG with anti-IgA, had any effect on the oxidative burst. These studies indicate that human monocytes have a receptor for sIgA and that specific activation of the monocytes occurs via these receptors.

Antigen-Antibody Complex↗

Lactoferrin inhibits prostaglandin E2 secretion by breast milk macrophages.

The interaction between human breast milk macrophages and lactoferrin (LF) in its native form was studied in in vitro culture. Competitive inhibition-binding studies with 125I-LF and unlabeled LF showed that a specific receptor for LF was present on breast milk macrophages. LF at concentrations of 10(-6) -10(-9)M resulted in a dose-dependent inhibition of prostaglandin E2 secretion by breast milk macrophages (control-45 +/- 7; LF 10(-6)M -9 +/- 1 ng/ml/10(6) cells). This inhibitory effect was also observed when the macrophages were stimulated with Concanavalin A (LF 10(-6) M -80 +/- 5; 10(-9) M -45 +/- 8% inhibition of prostaglandin E2 secretion by Concanavalin A stimulated macrophages). Lactalbumin and lactoglobulin had no effect. Similar concentrations of LF had no effect on lysozyme production. We also demonstrated that human milk macrophages are capable of eliciting an oxidative burst as measured by superoxide or hydrogen peroxide production when stimulated by phorbol myristate acetate in in vitro culture. (basal superoxide -1.4 +/- 0.3; phorbol myristate acetate 28.8 +/- 3.5 nmol/1 X 10(6) cells/90 min; basal hydrogen peroxide 11.7 +/- 4.6; phorbol myristate acetate -57.5 +/- 2.3 nmol/mg protein/90 min). LF had no effect on the oxidative burst. These results suggest that interaction of aqueous and cellular components of breast milk may occur and result in varied physiological effects.

Binding, Competitive↗

Effect of intralipid on the phagocytic and microbicidal capacity of human monocytes in culture.

We studied the effect of Intralipid (IL) in monocyte cultures based on the ability of the cultures to phagocytose and kill Candida albicans and produce the oxidative burst. The IL was taken up by monocytes in cultures, and these cells phagocytosed more Candida organisms than did the control cells [85 +/- 2.2% in the IL treated (1%) compared to 68 +/- 2.3% after 1 h in the control]. The percentage of killing of Candida albicans, which had been taken up by the IL-treated monocytes measured after 2 h in culture (48.3 +/- 6.0%), was no different when compared to control (47.0 +/- 5.8%). Following ingestion of IL, there was an increase in basal H2O2 production, however, the presence of the IL in the cells had no effect on the expected increase in H2O2 production following stimulation with either phorbol myristate acetate (PMA) or zymosan particles. Compared to untreated cells, a significant increase in the number of monocytes with positive nitroblue tetrazolium staining was observed in monocytes that had ingested IL (when they were stimulated with either PMA or Candida microorganisms). Similar results were obtained in monocyte-derived macrophages (i.e., monocytes in monolayer cultures for 10 days). These findings suggest that the essential monocyte functions of phagocytosis, microbicidal activity, and ability to elicit an oxidative burst are not directly altered by the conventional use of IL in clinical practice.

Candida albicans↗

Erythromelalgia following influenza vaccine in a child.

Erythromelalgia is a rare disease characterised by palmar and plantar erythema, burning pain and local increases in temperature. Erythromelalgia in adults most commonly appears secondary to myeloproliferative disorders, essential thrombocytosis and polycythemia vera; however, in children primary forms predominate. Erythromelalgia in children is characterised by a chronic relapsing course, usually refractory to treatment. We describe a case of erythromelalgia which developed in a 4.5 year old girl following influenza vaccination. Low dose aspirin, carbamazepine and propranolol induced a rapid resolution of the syndrome.

Aspirin↗

Juvenile Behçet's disease in Israel. The Pediatric Rheumatology Study Group of Israel.

OBJECTIVE: Behçet's disease (BD) is a vasculitis mainly observed in young adult males. Juvenile BD is rare and only small series of pediatric cases have been reported. The objective of this study was to define the epidemiology and clinical features of BD among Israeli children. METHODS: A questionnaire was sent to 8 pediatric rheumatology units in Israel and 30 cases of BD diagnosed before the age of 16 years were identified. RESULTS: Fifteen patients fulfilled the International Study Group Criteria for BD, while 15 had an incomplete form of BD. Among the patients with complete BD, stomatitis and skin involvement were the most common manifestations. Other symptoms included genital ulcers, uveitis, CNS involvement, arthritis, and gastrointestinal involvement. A positive family history was elicited in 3 patients. HLA B5 was found in 7 of 12 patients (58%). The 15 patients with incomplete BD all had recurrent stomatitis; other manifestations included uveitis, arthritis, and genital ulcers. HLA B5 was found in 94% of this group. CONCLUSION: Juvenile BD in Israel is not uncommon, and is frequently associated with HLA B5 positivity. This could indicate a genetic susceptibility in our region. Half of the patients in our series had an incomplete form of BD, which may represent a less severe variant of the disease. In any case, careful follow-up is required, since their condition could eventually evolve into complete BD.

Adolescent↗