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Biomedical subjects

Y Levy

Publications and source records attributed to Y Levy.

At least 91 records · Page 5Linked to original sources

Dermatomyositis and polymyositis associated with the antiphospholipid syndrome-a novel overlap syndrome.

OBJECTIVE: As APS (antiphospholipid syndrome) can be either primary or secondary to a wide range of other conditions (such as autoimmune diseases, malignancies, infectious diseases, and drug-induced conditions) the aim of this study was to describe a novel overlap syndrome of APS. METHODS: All patients diagnosed with either PM (polymytosis) or DM (dermatomytosis) who were treated in the Rheumatology Unit, Sheba Medical Center, were followed-up in the past 8 years for the appearance of a clinical manifestation of the APS, and conversely, patients with APS treated by us were clinically assessed for the presence of signs and symptoms of PM and DM. Both conditions were diagnosed according to accepted diagnostic criteria. RESULTS: Three patients were found to have both APS and PM/DM. A patient with PM had transverse myelopathy, a patient with DM had pulmonary embolism, and a patient with PM had recurrent abortions, stroke, livedo reticularis and mitral regurgitation. Both patients with PM had also SLE (systemic lupus erythematosis). CONCLUSIONS: APS can be associated with a wide range of diseases. Future data would reveal which therapy is the best for the association of PM/DM with APS, and determine the pathogenesis and prognosis in patients with this association.

Adult↗

Galectin-8 binding to integrins inhibits cell adhesion and induces apoptosis.

The interaction of cells with the extracellular matrix regulates cell adhesion, motility, growth, survival and differentiation through integrin-mediated signal transduction. Here we demonstrate that galectin-8, a secreted mammalian (beta)-galactoside binding protein, inhibits adhesion of human carcinoma (1299) cells to plates coated with integrin ligands, and induces cell apoptosis. Pretreatment of the cells with Mn(2+), which increases the affinity of integrins for their ligands, abolished the inhibitory effects of galectin-8. The inhibitory effects of galectin-8 were specific and were not mimicked by plant lectins or other galectins (galectin-1 and galectin-3). In accordance with its anti-adhesive effects, transfection of galectin-8 cDNA into 1299 cells significantly reduced (by 75%) colony formation, when compared to the number of colonies formed by cells transfected with an empty vector. Affinity chromatography over immobilized galectin-8 indicated that few membrane proteins interacted with galectin-8 in a sugar-dependent manner. Microsequencing and western immunoblotting revealed that (alpha)(3)(beta)(1 )integrin derived from 1299 as well as other cells (e.g. HeLa and human endothelial cells) is a major galectin-8 binding-protein. Furthermore, immunoprecipitation and immunohistochemical studies suggested that endogenous galectin-8, secreted from 1299 cells, forms complexes with (alpha)(3)(beta)(1) integrins expressed on the surface of 1299 cells. Galectin-8 also interacts with other members of the integrin family, like (alpha)(6)(beta)(1 )integrins. In contrast, galectin-8 only minimally interacts with (alpha)(4 )or (beta)(3 )integrins. We propose that galectin-8 is an integrin binding-protein that interacts to a different extent with several, but not all members of the integrin family. Binding of galectin-8 modulates integrin interactions with the extracellular matrix and thus regulates cell adhesion and cell survival.

Apoptosis↗

Detection of antibodies to gangliosides and glycolipids in various intravenous immunoglobulin (IVIg) preparations.

The aim of this study was to examine the presence of antibodies to GM1 and sulfatide in various IVIg preparations. Five brands of commercially available human IVIg (Sandoglobulin, Isiven, Cytogam, Omrigam and Cutter) were examined and compared. Serial dilutions of each of the above preparations were prepared at a working range of 0.009 to 25.0 mg/ml IVIg, and screened by a standard 96-well microplate EIA for autoantibodies to the ganglioside GM1 and to the glycolipid sulfatide. The various IVIg preparations (Omrigam, Cytogam, Sandoglobulin, Isiven), except for Cutter IVIg, contained low to medium titers of the autoantibodies tested. Omrigam and Cytogam IVIg contained low titer of antibodies to GM1, and medium-titer of antibodies to sulfatide, whereas Sandoglobulin and Isiven contained only low-titer of autoantibodies to sulfatide. The presence of natural autoantibodies to myelin in human sera may explain the presence of the tested antibodies within IVIg preparations. Measurements of antibodies to ganglioside and glycolipid in sera of Guillain-Barré patients immediately following IVIg, would probably not reveal antibody decrease. Alternatively, long-term (several weeks) follow-up of titers might result in their modification due to inhibition of antibodies production by IVIg.

Autoantibodies↗

Intensive chemotherapy (LNHIV-91 regimen) and G-CSF for HIV associated non-Hodgkin's lymphoma.

The purpose of the study was to evaluate the safety and long-term efficacy of an intensive chemotherapy regimen associated with G-CSF in HIV-associated non-Hodgkin's lymphoma (NHL). Fifty two consecutive patients with HIV infection, aggressive NHL and CD4+ cells > or = 100 x 10(6)/l were included. The median CD4 cell count was 276 x 10(6)/l. Nineteen tumors were of the Burkitt's type, 23 were large cells, 7 immunoblastic, and 3 anaplastic. Twenty-five patients had stage IV disease (bone marrow involvement in 7, and central nervous system in 9). Three cycles of ACVBP (doxorubicine, cyclophosphamide, vindesine, bleomycin, prednisolone) were given. A fourth cycle was delivered to patients in partial remission or with initial bulky disease. The induction was followed by three cycles of CVM (cyclophosphamide, etoposide, methotrexate). G-CSF 5 microg/kg was used at each cycle. Results showed that 37 patients (71%) achieved a complete remission. With a median follow-up of 74 months, 8 of them have relapsed. The median survival was 15 months and 34 patients have died (21 with NHL). The 4-year estimate survival was 33.9% (95% CI, 19.8%-47.4%). The Relative Dose-Intensity of the chemotherapy was 85% for doxorubicine and 87% for cyclophosphamide. In a multivariate analysis, homosexual men and patients with ECOG < 2 had a lower risk for death: RR = 0.32 (95% CI, 0.15-0.65) and RR = 0.36 (95% CI, 0.18-0.74), respectively. Achievement of complete remission was strongly associated with survival. In conclusion, it seems that in HIV-infected patients with NHL and a CD4 cell count above 100 x 10(6)/l, high complete remission rate and prolonged survival can be achieved with the intensive LNHIV-91 regimen.

Actuarial Analysis↗

Selected abstracts

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Journal Article↗

The prevalence of specific IgE antibodies to natural rubber latex in healthcare workers in Israel.

BACKGROUND: According to studies from different countries, the prevalence of natural rubber latex sensitization in healthcare workers ranges from 2.9 to 17%. OBJECTIVE: To estimate the prevalence of NRL-specific IgE antibodies in healthcare workers in Israel. METHODS: Three hundred healthcare workers, mostly from a major pediatric tertiary care facility, and 15 non-healthcare workers completed a questionnaire on signs and symptoms of NRL allergy and other respiratory and food allergies. NRL-specific IgE antibodies were assayed with the DPC AlaSTAT-ELISA method. RESULTS: Seventy of the 300 workers (23.3%) reported symptoms of NRL allergy: hand eczema and pruritus in 63, upper respiratory tract and ocular symptoms in 10, shortness of breath in 2, and generalized rash in 6. None had anaphylaxis due to latex exposure. There was a significant correlation of symptoms of NRL allergy with atopy and job category (nurses, laboratory technicians, nurse assistants and dental medicine workers), but not with gender, age, or years of employment. The in vitro tests for specific IgE antibodies against NRL were positive (> or = 0.70 IU/ml) in five workers (1.66%). CONCLUSIONS: This is the first study of the prevalence of NRL-specific IgE antibodies in healthcare workers in Israel. Our 1.66% sensitization rate is much lower than that reported for healthcare workers in other countries. This difference may be due to our inclusion of a study population with a relatively low exposure to latex gloves (pediatricians compared to surgeons). Further studies are needed in this and other high risk populations in Israel.

Dermatitis, Atopic↗

Impairment in quality of life among patients seeking surgery for hyperhidrosis (excessive sweating): preliminary results.

BACKGROUND: The present paper describes the initial stages of the development and administration of a short, disease-specific, health related questionnaire to assess the impact of suffering from hyperhidrosis (excessive sweating) on the Quality of Life (QoL) of patients who are anticipating surgery for this disorder. METHOD: The study was performed in two stages: 1. The life domains in which the condition impairs QoL were assessed by in-depth interviews with 10 patients suffering from hyperhidrosis. 2. A questionnaire covering five life domains was built based on these interviews. 3. This questionnaire was administered to 48 patients, 30 females and 18 males between the ages 15 and 48. RESULTS: Results showed that subjective QoL was significantly lower among females in four of the five life areas and that duration of the condition correlates with a lower quality of life. A regression analysis showed that the subjective suffering of the patients was explained mainly by social aspects. CONCLUSIONS: The questionnaire is a novel attempt to assess QoL in a disorder with strong esthetic and social consequences and could improve communication between patients and their physicians.

Adult↗

[Pulmonary adenocarcinoma in myasthenia gravis--autoimmunity and late development of malignancy].

We report a 75-year-old man with myasthenia gravis for many years, who was hospitalized because of cough, fever, and dyspnea. Chest x-ray revealed a bilateral pleural effusion. Adenocarcinomatous cells were found in the pleural fluid. Computerized tomography of the chest showed widespread pulmonary dissemination of the tumor. The relationship between myasthenia gravis, an autoimmune disease involving the motor end-plate, and malignancy (thymoma) has been widely recognized. Current literature documents few reports of lung malignancies with concurrent development of myasthenia gravis. A tentative explanation, based on current research, is provided for the possible role of myasthenia gravis and the late development of lung cancer. Moreover, a model for the autoimmune phenomenon and the development of late malignancies is provided with explicit explanations. It is important to search for occult, developing malignancies in newly diagnosed autoimmune diseases.

Adenocarcinoma↗

Acute activation of CD8+ T lymphocytes in interleukin-2-treated HIV-infected patients. ANRS-048 IL-2 Study Group. Agence Nationale de Recherches sur le SIDA.

CD8+ T lymphocytes play a key role in the control of HIV infection, through both cytotoxic and noncytotoxic mechanisms. To study in vivo effects of interleukin-2 (IL-2) treatment on this cell compartment, the level of activation of CD8+ T lymphocytes was evaluated before and just after 5-day administration of IL-2 in 16 HIV-infected patients. The serum level of soluble CD25 and of soluble CD8 significantly increased following IL-2 administration. The number of mRNA molecules coding for perforin and granzyme B, two enzymes that are contained in granules of cytotoxic cells, also significantly increased in peripheral blood mononuclear cells and in purified CD8+ cells (p < .001). Variations of plasma HIV viremia and perforin gene expression following IL-2 administration were inversely correlated (p = .023), suggesting that IL-2-induced activation of CD8+ T lymphocytes contributes to limit HIV replication in vivo. In contrast to perforin and granzyme B gene expression, IL-2 administration did not increase the expression of macrophage inhibitory protein-1alpha (MIP-1alpha), MIP-1beta, and regulated-on-activation normal T-expressed and secreted (RANTES) genes. These findings indicate that CD8+ T lymphocytes in HIV-infected patients are acutely activated by IL-2 treatment, which may improve long-term control of HIV infection.

CD8 Antigens↗

Comparison of subcutaneous and intravenous interleukin-2 in asymptomatic HIV-1 infection: a randomised controlled trial. ANRS 048 study group.

BACKGROUND: Intermittent interleukin-2 therapy for HIV-1 by continuous intravenous infusion leads to sustained increase of CD4 T cells. This method of administration is, however, inconvenient and has limiting toxic effects. We did a randomised study to compare safety and efficacy of antiviral treatment alone or combined with various interleukin-2 regimens in HIV-1-infected patients. METHODS: 94 symptom-free patients, naïve to antiretroviral treatment, with CD4-T-cell counts of 250-550 cells/microL at baseline were randomly assigned zidovudine and didanosine alone (n=26) or combined with interleukin-2 administered intravenously (12 million IU/day, n=22) or subcutaneously (3 million IU/m2 twice daily, n=24) for 5 days, or were given polyethylene-glycol-modified (PEG) interleukin-2 (2 million IU/m2 intravenous bolus, n=22) administered every 2 months from week 2 to week 50 (seven cycles). Safety and immunological and virological results were monitored until week 56. FINDINGS: CD4-T-cell count increased to higher than baseline by a mean of 564 cells/microL (subcutaneous group), 676 cells/microL (intravenous group), 105 cells/microL (PEG group), and 55 cells/microL (antiretroviral-therapy group, p=0.0001). 68% and 77% of patients in the subcutaneous and intravenous groups, respectively, achieved an 80% increase of CD4 T cells (p<0.001). In these two groups, 50% of patients restored a CD4/CD8-T-cell ratio of more than 1. The groups did not differ significantly for changes in plasma HIV-1 RNA loads throughout the study. The duration of common side-effects of interleukin-2 was shorter in the subcutaneous group, which enabled outpatient treatment. Naïve and memory CD4 T cells, CD28 expression on CD4 and CD8 T cells, and restoration of in-vitro proliferative response to mitogens and recall antigens increased in the intravenous and subcutaneous groups. INTERPRETATION: Subcutaneous interleukin-2 is a convenient regimen that, as well as intravenous therapy, improves immunological function in HIV-1-infected patients receiving two nucleosides. Larger studies are needed to show whether immunological improvements translate into clinical benefit.

Adult↗

Anti-oxidized low density lipoprotein antibody determination as a predictor of restenosis following percutaneous transluminal coronary angioplasty.

Recent data suggests that autoimmune factors play an important role in the pathogenesis of atherosclerosis. In this context several autoantigens have been shown to elicit an immune response that results in accelerated atherosclerotic plaque formation. In the present study, we investigated whether elevated titers of anti-oxidized low density lipoprotein (oxLDL), anticardiolipin and antibodies to beta2-glycoprotein I (beta2GPI) can predict subsequent restenosis in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). A total of 74 consecutive patients (52 males, 22 females) with coronary artery disease were enrolled in the study. All patients underwent successful PTCA prior to which blood was drawn for the antibody analysis. The PTCA was followed by a clinical evaluation. Patients with recurrent chest pains underwent a repeated angiography and 34 of the 74 patients (46%) experienced restenosis. Patients positive for the presence of anti-oxLDL antibodies were more likely to develop restenosis within 6 months when compared with patients with no subsequent restenosis (relative-risk of 1.87; P< 0.05). Presence of anti-oxLDL antibodies was associated with hyperlipidemia (r = 0.25; P < 0.05) but not with other risk factors for atherosclerosis. Positivity for anticardiolipin or anti-beta2GPI antibodies which associate with a prothrombotic state, was not effective in predicting lumen narrowing. Thus, the presence of elevated levels of anti-oxLDL antibodies is associated with a higher risk for coronary restenosis following PTCA.

Aged↗

[Relapse of sarcoidosis after alternative medical treatment].

Reference to alternative medicine frequently appears in newspaper headlines, advertisements and in articles in medical journals. The practice of alternative medicine has increased, even as the number of critical articles warning of deleterious effects have also increased. Public demand is strong and growing, but there are no clear rules as to what is not permissible, particularly when treatment is not by qualified physicians. There are still no clear indications and contraindications for complementary (not alternative) medicine in patients with organic injuries and life-threatening conditions. However, it is obvious that in these patients complementary medicine should not be substituted for conventional therapy. We present a 32-year-old man with sarcoidosis who discontinued conventional therapy on his own initiative and began alternative medicine (homeopathy) with subsequent deterioration in his condition. He was hospitalized for a relapse of his sarcoidosis which required large doses of corticosteroids.

Adrenal Cortex Hormones↗

Immunolocalization of beta2-glycoprotein I (apolipoprotein H) to human atherosclerotic plaques: potential implications for lesion progression.

BACKGROUND: beta2-Glycoprotein I (beta2GPI) is a major antigenic target of antiphospholipid antibodies, which possesses natural anticoagulant properties. The aim of the present study was to determine its presence and localization within human atherosclerotic plaques and to study its association with endothelial cells and monocyte macrophages in vitro. METHODS AND RESULTS: Human atherosclerotic lesions were obtained after carotid endarterectomies and studied immunohistochemically with anti-beta2GPI as well as antibodies to CD4/CD8, macrophages, and adhesion molecules. In vitro, human umbilical vein endothelial cells (HUVECs) and U937 (myelomonocytic cell line) cells were investigated for their ability to associate with radiolabeled beta2GPI. We found beta2GPI to be abundantly expressed within the subendothelial regions and intimal-medial borders of human atherosclerotic plaques and to colocalize with CD4-positive lymphocytes. This observation was confirmed by Western blot applied on homogenates of atherosclerotic lesions with anti-beta2GPI antibodies. Both HUVECs and U937 cells bound labeled beta2GPI, and the process was inhibited by oxidized LDL and not by native LDL. CONCLUSIONS: The abundant presence of human beta2GPI within the lesions, its association with endothelial cells and macrophages, and its colocalization with CD4-positive lymphocytes suggests that it may serve as a target for an immune-mediated reaction that can influence lesion progression.

Animals↗

Acute upregulation of CCR-5 expression by CD4+ T lymphocytes in HIV-infected patients treated with interleukin-2. ANRS 048 IL-2 Study Group.

BACKGROUND: The treatment of HIV-infected patients with interleukin (IL)-2 causes a sustained increase in CD4+ T-lymphocyte counts, involving both naive and memory cells. However, the short-term immunological effects of IL-2, which may shed light on the mechanism of immune reconstitution by this cytokine, are unknown. OBJECTIVE: To evaluate the acute effect of IL-2 on circulating T-lymphocyte subpopulations and their expression of chemokine receptors. DESIGN AND METHODS: Flow cytometry, reverse transcriptase polymerase chain reaction and chemokine receptor function experiments were performed before and after 5 days of IL-2 administration in 30 HIV-infected patients. RESULTS: IL-2 induced an acute lymphopenia of both naive and memory T-helper (TH) lymphocytes. This was associated with a large increase in CC-chemokine receptor (CCR)-5 and CCR-2b expression by TH cells. Before IL-2 treatment, CCR-5 was mostly produced by CD62L- memory TH lymphocytes. After 5 days of IL-2 administration, the level of CCR-5 mRNA in circulating cells was 18.6 times higher than before treatment (P < 0.002). CCR-5 expression was upregulated in CD62L- memory TH lymphocytes, but also in CD62L+ memory and in naive (CD62L+ CD45RO-) TH lymphocytes. IL-2 treatment also increased the function of CCR-5 in TH cells. CONCLUSIONS: Chemokine receptors are involved in trafficking of lymphocytes. The IL-2-induced upregulation of chemokine receptors in TH cells may thus play a role in the acute effects of this cytokine in TH lymphocyte redistribution.

Adult↗