16 results on '"Arad, Ariela"'
Search Results
2. β2-glycoprotein-1 autoantibodies from patients with antiphospholipid syndrome are sufficient to potentiate arterial thrombus formation in a mouse model
- Author
-
Arad, Ariela, Proulle, Valerie, Furie, Richard A., Furie, Barbara C., and Furie, Bruce
- Abstract
Antiphospholipid syndrome is characterized by thrombosis, recurrent fetal loss, and the presence of the lupus anticoagulant, anticardiolipin antibodies, or anti–β2-glycoprotein-1 (anti–β2-GP1) antibodies. Although anti–β2-GP1 antibodies have been documented as a biomarker for diagnosis of antiphospholipid syndrome, their direct role in the pathogenesis of thrombosis is unknown. We have demonstrated using intravital microscopy that anti–β2-GP1 autoantibodies purified from the sera of patients with antiphospholipid syndrome complicated by thrombosis greatly amplify thrombus size after laser-induced vessel wall injury in live mice. Anti–β2-GP1 autoantibodies from 3 patients with antiphospholipid syndrome were affinity-purified using human β2-GP1 bound to agarose. The effects of purified anti–β2-GP1 IgG autoantibodies, of anti–β2-GP1–depleted IgG, and of IgG from normal human sera on thrombus formation were measured in mice after arterial injury in the cremaster muscle. Before injury, purified anti–β2-GP1 IgG autoantibodies, anti–β2-GP1 antibody–depleted IgG, or IgG from normal human sera were infused. Increasing amounts of purified anti–β2-GP1 autoantibodies increased thrombus size in a dose-dependent manner, whereas neither anti–β2-GP1 antibody-depleted IgG nor IgG from normal serum affected thrombus size. These results indicate that anti–β2-GP1 IgG autoantibodies in antiphospholipid syndrome patient sera are not only a marker of antiphospholipid syndrome but are directly involved in the pathogenesis of thrombosis.
- Published
- 2011
- Full Text
- View/download PDF
3. β2-glycoprotein-1 autoantibodies from patients with antiphospholipid syndrome are sufficient to potentiate arterial thrombus formation in a mouse model
- Author
-
Arad, Ariela, Proulle, Valerie, Furie, Richard A., Furie, Barbara C., and Furie, Bruce
- Abstract
Antiphospholipid syndrome is characterized by thrombosis, recurrent fetal loss, and the presence of the lupus anticoagulant, anticardiolipin antibodies, or anti–β2-glycoprotein-1 (anti–β2-GP1) antibodies. Although anti–β2-GP1 antibodies have been documented as a biomarker for diagnosis of antiphospholipid syndrome, their direct role in the pathogenesis of thrombosis is unknown. We have demonstrated using intravital microscopy that anti–β2-GP1 autoantibodies purified from the sera of patients with antiphospholipid syndrome complicated by thrombosis greatly amplify thrombus size after laser-induced vessel wall injury in live mice. Anti–β2-GP1 autoantibodies from 3 patients with antiphospholipid syndrome were affinity-purified using human β2-GP1 bound to agarose. The effects of purified anti–β2-GP1 IgG autoantibodies, of anti–β2-GP1–depleted IgG, and of IgG from normal human sera on thrombus formation were measured in mice after arterial injury in the cremaster muscle. Before injury, purified anti–β2-GP1 IgG autoantibodies, anti–β2-GP1 antibody–depleted IgG, or IgG from normal human sera were infused. Increasing amounts of purified anti–β2-GP1 autoantibodies increased thrombus size in a dose-dependent manner, whereas neither anti–β2-GP1 antibody-depleted IgG nor IgG from normal serum affected thrombus size. These results indicate that anti–β2-GP1 IgG autoantibodies in antiphospholipid syndrome patient sera are not only a marker of antiphospholipid syndrome but are directly involved in the pathogenesis of thrombosis.
- Published
- 2011
- Full Text
- View/download PDF
4. Efficacy of Topical Application of Eosin Compared with Zinc Oxide Paste and Corticosteroid Cream for Diaper Dermatitis
- Author
-
Arad, Ariela, Mimouni, Daniel, Ben-Amitai, Dan, Zeharia, Avraham, and Mimouni, Marc
- Abstract
Background:Corticosteroids, zinc paste and eosin 2% are well-known topical agents for the treatment of moderate to severe diaper dermatitis. Among these treatments, the aqueous solution of eosin 2% is extensively used in several European countries, but not in the USA or Israel. Objective:To assess the therapeutic efficacy of eosin 2% solution compared to the other treatment modalities for diaper dermatitis. Methods:Fifty-four infants with diaper dermatitis, recruited from hospital wards and community clinics, were randomly assigned to three treatment groups: zinc oxide paste (containing allantoin 0.5%, cod liver oil 17% and zinc oxide 47epercnt;); clobetasone butyrate 0.05%, and aqueous solution of eosin 2%. The severity of the disorder was graded on a 6-point scale by observation and quantitative measurement of the lesions. The groups were compared for rates and time to heal. Due to the red color of eosin, a double-blind controlled study was impossible. Results:Following 5 days of treatment, the rate of complete healing in the group treated with eosin (61%) was significantly higher (p = 0.0479) than that in the zinc oxide paste and corticosteroid groups (22 and 33%, respectively). Furthermore, in cases of partial healing, the degree of improvement was higher in the eosin group than the other two (p = 0.0205). The fastest improvement was observed in the group treated with corticosteroid cream. Conclusion:Considering the potential hazards of topical corticosteroids and the greater overall efficacy of eosin 2% solution, we suggest that eosin is the preferred treatment for diaper dermatitis.
- Published
- 1999
- Full Text
- View/download PDF
5. A Novel Risk-Model to Predict Time to First Treatment (TTT) in Chronic Lymphocytic Leukemia Based on Heavy+Light Chain Immunoparesis and Serum Free Light Chain Analysis: Results from the Israeli CLL Study Group
- Author
-
Tadmor, Tamar, Braester, Andrei, Dally, Najib, Aviv, Ariel, Herishanu, Yair, Yuklea, Mona, Shvidel, Lev, Rahimi-Levene, Naomi, Ruchlemer, Rosa, Arad, Ariela, Fogl, Claudia, Polliack, Aaron, Magal, Lee, and Townsend, Kelly
- Abstract
Tadmor: PFIEZER: Consultancy; JNJ: Consultancy; ABBVIE: Consultancy; NOVARTIS: Consultancy; ROCHE: Research Funding. Aviv:ABBVIE: Consultancy; ROCHE: Research Funding. Herishanu:ROCHE: Research Funding; JNJ: Consultancy; ABBVIE: Consultancy. Shvidel:ROCHE: Consultancy, Research Funding; ABBVIE: Consultancy, Research Funding; JNJ: Consultancy. Rahimi-Levene:ABBVIE: Consultancy. Ruchlemer:ABBVIE: Consultancy; JNJ: Consultancy. Fogl:The Binding Site Group Ltd: Employment. Polliack:ROCHE: Research Funding; ABBVIE: Consultancy. Magal:The Binding Site: Employment. Townsend:The Binding Site Group Ltd: Employment.
- Published
- 2018
- Full Text
- View/download PDF
6. A Novel Risk-Model to Predict Time to First Treatment (TTT) in Chronic Lymphocytic Leukemia Based on Heavy+Light Chain Immunoparesis and Serum Free Light Chain Analysis: Results from the Israeli CLL Study Group
- Author
-
Tadmor, Tamar, Braester, Andrei, Dally, Najib, Aviv, Ariel, Herishanu, Yair, Yuklea, Mona, Shvidel, Lev, Rahimi-Levene, Naomi, Ruchlemer, Rosa, Arad, Ariela, Fogl, Claudia, Polliack, Aaron, Magal, Lee, and Townsend, Kelly
- Abstract
Introduction:
- Published
- 2018
- Full Text
- View/download PDF
7. Early Bone Marrow Examination, On The Fifth Day Of Induction For AML, Is Highly Predictive Of Response
- Author
-
Ofran, Yishai, Hayun, Michal, Leiba, Ronit, Zuckerman, Tsila, Horowitz, Netanel, Hoffman, Ron, Benyamini, Noam, Sabag, Elinor, Klil, Adi, Khatib, Alaa, Lavi, Noa, Henig, Israel, Brenner, Benjamin, Gatt, Moshe E., Hellmann, Ilana, Arad, Ariela, Bulvik, Shlomo, Gino-Moor, Sharon, Ganzel, Chezi, Saban, Revital, Tvito, Ariella, and Rowe, Jacob M.
- Abstract
Bone marrow blast count on the fifth day of induction during chemotherapy is a powerful predictor of AML prognosis, irrespective of other pre-treatment risk factors. Larger studies, with longer follow up are required to determine its role in clinical management.No relevant conflicts of interest to declare.
- Published
- 2013
- Full Text
- View/download PDF
8. Richter’s Syndrome In Chronic Lymphocytic Leukemia: Clinical and Laboratory Features In 119 Patients, Attempting To Identify Possible Risk Factors
- Author
-
Tadmor, Tamar, Fineman, Riva, Shvidel, Lev, Bairey, Osnat, Goldschmidt, Neta, Ruchlemer, Rosa, Rachimi, Naomi Rahimi, Herishanu, Yair, Yuklea, Mona, Arad, Ariela, Aviv, Ariel, and Polliack, Aaron
- Abstract
Richter's syndrome (RS) is the rare development of an aggressive lymphoid malignancy in a patient with pre-existing, or concomitant chronic lymphocytic leukemia (CLL). This complication occurs in about 5 % of patients with CLL, and the most frequent form is the development of diffuse large B-cell lymphoma (DLBCL) and less frequently Hodgkin lymphoma (HL) or prolymphocytic leukemia (PLL). Most of the available data on RS is derived from case reports or small series of patients, and only a few larger cohorts have been published.The purpose of this retrospective study was to summarize our experience with RS in CLL, examine possible risk factors and analyze relevant demographic, laboratory and clinical parameters, including outcome.We collected a total of 119 patients diagnosed with RS from 12 medical centers in Israel during the period 1971-2010.We then summarized clinical, demographic and some biological features related to CLL at diagnosis and examined possible risk factors for their transformation to RS.Of the 119 patients with RS, 61 % were males, 82% developed DLBCL, 14% HL and 4% PLL. In terms of ethnicity: 95% were Jews (64% Ashkenazi) and only 5 % were Arabs, which is similar to the reported data for CLL in Israel.The median time from CLL diagnosis to development of RS was 60 months (range, 0-182 months), and the median overall survival from diagnosis of RS was 9.5 months;34 % of the cases developed extranodal RS, and the most frequent sites of involvement were the gastro-intestinal tract and bone marrow. These results further confirm that there are no established “sanctuary sites” of extranodal RS, which can develop in all tissues and organs.None of the conventional clinical and laboratory parameters examined and evaluated as possible risk factors in CLL were able to predict transformation to RS, including: occurrence of autoimmune phenomenon during the course of CLL, spleen size, serum beta 2 microglobulin levels, degree of CD38 positivity, and the number of previous treatments given for CLL, or the prior use of rituximab in these regimens.The only parameters, present at the time of RS diagnosis which were found to correlate with adverse prognosis, included: performance status>2 (HR- 3.45), high IPI (HR- 3.28) and high Richter score (HR-7.45). In regard to therapy for RS, patients treated with chemotherapy followed by autologous stem cell transplantation (ASCT) had a better outcome with improved overall survival (p=0.034) (Figure).RS remains a heterogeneous entity. In this large series of patients none of the conventional clinical, epidemiological or laboratory parameters, often evaluated as possible prognostic factors in CLL, were associated with the risk of transformation to RS. In this retrospective study molecular genetic data were not available to examine their possible significance, as reported recently in other series.In terms of therapy, prior treatment of CLL with rituximab – containing regimens did not appear to impact the eventual outcome of patients who developed RS. On the other hand, ASCT did significantly improve overall survival in patients who had transformation to RS.On behalf the Israeli CLL study Group.No relevant conflicts of interest to declare.
- Published
- 2013
- Full Text
- View/download PDF
9. Richter's Syndrome In Chronic Lymphocytic Leukemia: Clinical and Laboratory Features In 119 Patients, Attempting To Identify Possible Risk Factors
- Author
-
Tadmor, Tamar, Fineman, Riva, Shvidel, Lev, Bairey, Osnat, Goldschmidt, Neta, Ruchlemer, Rosa, Rachimi, Naomi Rahimi, Herishanu, Yair, Yuklea, Mona, Arad, Ariela, Aviv, Ariel, and Polliack, Aaron
- Abstract
Richter's syndrome (RS) is the rare development of an aggressive lymphoid malignancy in a patient with pre-existing, or concomitant chronic lymphocytic leukemia (CLL). This complication occurs in about 5 % of patients with CLL, and the most frequent form is the development of diffuse large B-cell lymphoma (DLBCL) and less frequently Hodgkin lymphoma (HL) or prolymphocytic leukemia (PLL). Most of the available data on RS is derived from case reports or small series of patients, and only a few larger cohorts have been published.
- Published
- 2013
- Full Text
- View/download PDF
10. Early Bone Marrow Examination, On The Fifth Day Of Induction For AML, Is Highly Predictive Of Response
- Author
-
Ofran, Yishai, Hayun, Michal, Leiba, Ronit, Zuckerman, Tsila, Horowitz, Netanel, Hoffman, Ron, Benyamini, Noam, Sabag, Elinor, Klil, Adi, Khatib, Alaa, Lavi, Noa, Henig, Israel, Brenner, Benjamin, Gatt, Moshe E., Hellmann, Ilana, Arad, Ariela, Bulvik, Shlomo, Gino-Moor, Sharon, Ganzel, Chezi, Saban, Revital, Tvito, Ariella, and Rowe, Jacob M.
- Published
- 2013
- Full Text
- View/download PDF
11. Predictive Parameters for Infections During Azacitidine Therapy in High Risk MDS Patients,
- Author
-
Merkel, Drorit, Filanovsky, Kalman, Aviv, Ariel, Gatt, Moshe E., Herishanu, Yair, Arad, Ariela, Tadmor, Tamar, Dally, Najib, Ronson, Aharon, Akria, Luiza, Braester, Andrei, Nagler, Arnon, Leiba, Ronit, and Ofran, Yishai
- Abstract
Azacitidine is an effective therapy for high risk myelodysplastic syndrome (MDS). Neutropenic fever is a common life threatening complication during azacitidine therapy, however predicting it, is challenging. Despite a number of large scale prospective studies, there are no established indications for primary or secondary prophylactic antibiotics or for the use of granulocyte colony-stimulating factor (G-CSF) (Pierre Fenauxa et al. Leukemia Research 2010). We used a retrospective survey of 98 high risk MDS and AML patients treated with Azacitidine, to develop a predicting model for infection during each cycle of Azacitidine therapy.We retrospectively studied 82 high risk MDS and 16 AML patients treated with 456 azacitidine cycles between 9.2008 and 7.2011at 11 institutions from Israel. Information, of complete blood count, creatinine and liver enzymes was documented prior to initiation of each cycle.Patients' median age was 71 (range 27–92) and 57 (58%) of them males. Poor cytogenetic abnormalities were detected in 30.8% (25 of 82 patients with available cytogenetic) and 65 (67%) were transfusions dependent. The median interval between the initial diagnosis and the initiation of azacitidine therapy was 187 days (range 4 days – 18 years). Azacitidine was administrated as first line therapy in 24 (24%) of patients, 37 (38%) had failed growth factors, 5 (5%) were relapsing after allogeneic transplantation and 32 (33%) were given different chemotherapies prior to azacitidine therapy. Doses and schedule of azacitidine data were available for 98% (446/456) of cycles. The prevalence of 7 days cycles of 75mg/m2, 5 days cycles of 75mg/m2 or attenuated doses were 50.4%, 30%, 16.9% respectively.Adverse events were obtained from patient's charts. 13 major bleeding and 78 infections episodes (2.85% and 16.9% of all cycles) were recorded. Due to the low number of bleeding events we focused on factors predicting infection episodes. Infection rates of 22.7%, 14.2% and 6.9% correlated with azacitidine dose (75mg/m2x7d Vs 5d) and lower respectively). Excluding 87 cycles of doses lower than 75mg/m2 for 5 days, predictors of infections were evaluated in 369 cycles.Nine parameters were included in final analysis: age, sex, cytogenetics, being transfusion dependent prior to first cycle, time from diagnosis to the first cycle, azacitidine dose and neutrophil, thrombocyte and creatinine values prior to each cycle. The odd ratio off infections related to neutrophils count was higher than ANC, so we used neutrophils counts as a predictor. For each cycle we considered full 7 days Vs 5 days schedule, neutrophil above or below 500 cells/mcl, platelet above or below 20,000 cells/mcl and creatinine level prior to the first day of cycle. In univariate analysis neutrophil below 500, platelet below 20,000, creatinine level, azacitidine dose and being transfusion dependent were correlated with infection. In a multivariate analysis (table 1) transfusion dependency and platelets lower than 20,000 were the only significant parameters. Risk of infection was higher when a full seven days cycle was administrated but haven't reach statistical significance (p=0.07).Transfusion dependency prior to first cycle and platelets lower than 20,000 prior to each cycle, are the main significant risk factors for infections during azacitidine therapy. Neutropenia and age are known risk factors for infections in general, but were not significant in our study. We assume that in high risk MDS patients when most off the patients are old and neutropenic, thrombocytopenia is a surrogate marker of disease status which makes the patient more prone to infections. Therefore physicians should considerer these two parameters prior to every azacitidine cycle as guidance in the debate of concurrent prophylactic antibiotics, G-CSF or a tolerable dose of azacitidine. Our findings should be confirmed in a larger sample set but may pave the road for prospective studies of infection prophylaxis during azacitidine therapy.No relevant conflicts of interest to declare.
- Published
- 2011
- Full Text
- View/download PDF
12. Predictive Parameters for Infections During Azacitidine Therapy in High Risk MDS Patients,
- Author
-
Merkel, Drorit, Filanovsky, Kalman, Aviv, Ariel, Gatt, Moshe E., Herishanu, Yair, Arad, Ariela, Tadmor, Tamar, Dally, Najib, Ronson, Aharon, Akria, Luiza, Braester, Andrei, Nagler, Arnon, Leiba, Ronit, and Ofran, Yishai
- Abstract
Abstract 3811
- Published
- 2011
- Full Text
- View/download PDF
13. Affinity-Purified Anti-Beta-2 Glycoprotein-1 Antibodies from a Patient with Lupus Anticoagulant-Associated Thrombosis Amplify Thrombus Formation in the Living Mouse.
- Author
-
Arad, Ariela, Furie, Richard A, Furie, Barbara C, and Furie, Bruce
- Abstract
No relevant conflicts of interest to declare.
- Published
- 2009
- Full Text
- View/download PDF
14. Affinity-Purified Anti-Beta-2 Glycoprotein-1 Antibodies from a Patient with Lupus Anticoagulant-Associated Thrombosis Amplify Thrombus Formation in the Living Mouse.
- Author
-
Arad, Ariela, Furie, Richard A, Furie, Barbara C, and Furie, Bruce
- Abstract
Abstract 146
- Published
- 2009
- Full Text
- View/download PDF
15. Upregulation of Human Pim-2 in B-CLL, Involves Interactions between Oct-1, Oct-2, Bob-1 and NF-kB.
- Author
-
Dicken, Yosef, Cohen, Amos M., Bessler, Hanna, Levi-Hirsh, Daphna, Arad, Ariela, Merkel, Drorit, and Don, Jeremy
- Abstract
hPim-2 is a proto-oncogene that encodes a serine/threonine kinase and inhibits apoptosis by phosphorylation of BAD. We have shown that hPim is upregulated in human non-Hodgkin’s lymphomas (NHL) and in chronic lymphocytic leukemia (B-CLL) and its cellular transcript levels in B-CLL correlates with lymphocyte doubling time. We found no mutations in the promoter region of hPim-2 in B-cells of 30 patients with CLL (~2000 bp upstream). The proximal promoter region of hPim-2 (600 bp) contains two adjacent NF-kB-binding elements, two adjacent Oct-binding elements and an SP1 element by bioinformatic analysis. Studies have recently shown that the transcription factor Oct-2 and the B-cell specific Oct cofactor Bob-1 are overexpressed in certain large B-cell lymphomas, whereas increased expression of Bob-1 has also been observed in T-cell neoplasms. Shift assays (EMSA) analysis, using nuclear extracts from B-CLL cells and various fragments of hPim-2 promoter region used as probes, revealed that complexes containing an Oct elements were consistently heavier in B-CLL extracts compared with control B-cells. Accordingly, Oct-1, Oct-2 and Bob-1 protein levels were significantly higher in B-CLL compared to healthy extracts. Moreover, chromatin immunoprecipitation (Chip) assays confirmed that in-vivo Oct-1+2 and Bob-1 are indeed physically attached to the hPim-2 promoter, and that this interaction is significantly more intensive in B-CLL cells than in control B-cells. Furthermore, we have found in addition that the p52 isoform subunit of NF-kB predominates the interaction with the kB element in the hPim-2 promoter in B-CLL cells, as compared to the p50 isoform observed in control B-cells. To determine whether these interactions are transcriptionaly significant, we fused the luciferase reporter gene to various promoter fragments, and monitored luciferase expression in-vitro after incubation with either B-CLL or normal B-cell extracts. Luciferase expression was consistently higher when Oct element-containing fragment was incubated with B-CLL cell extracts. Together, these results suggest that the upregulation of hPim-2 in B-CLL is due to enhanced expression and transcriptional activity of the Oct-1+2 and Bob-1 complex and that it might synergistically act with the p52 containing NF-kB transcription factor.
- Published
- 2004
- Full Text
- View/download PDF
16. Upregulation of Human Pim-2in B-CLL, Involves Interactions between Oct-1, Oct-2, Bob-1 and NF-kB.
- Author
-
Dicken, Yosef, Cohen, Amos M., Bessler, Hanna, Levi-Hirsh, Daphna, Arad, Ariela, Merkel, Drorit, and Don, Jeremy
- Abstract
hPim-2is a proto-oncogene that encodes a serine/threonine kinase and inhibits apoptosis by phosphorylation of BAD. We have shown that hPim is upregulated in human non-Hodgkin's lymphomas (NHL) and in chronic lymphocytic leukemia (B-CLL) and its cellular transcript levels in B-CLL correlates with lymphocyte doubling time. We found no mutations in the promoter region of hPim-2 in B-cells of 30 patients with CLL (~2000 bp upstream). The proximal promoter region of hPim-2(600 bp) contains two adjacent NF-kB-binding elements, two adjacent Oct-binding elements and an SP1 element by bioinformatic analysis. Studies have recently shown that the transcription factor Oct-2 and the B-cell specific Oct cofactor Bob-1 are overexpressed in certain large B-cell lymphomas, whereas increased expression of Bob-1 has also been observed in T-cell neoplasms. Shift assays (EMSA) analysis, using nuclear extracts from B-CLL cells and various fragments of hPim-2 promoter region used as probes, revealed that complexes containing an Oct elements were consistently heavier in B-CLL extracts compared with control B-cells. Accordingly, Oct-1, Oct-2 and Bob-1 protein levels were significantly higher in B-CLL compared to healthy extracts. Moreover, chromatin immunoprecipitation (Chip) assays confirmed that in-vivoOct-1+2 and Bob-1 are indeed physically attached to the hPim-2 promoter, and that this interaction is significantly more intensive in B-CLL cells than in control B-cells. Furthermore, we have found in addition that the p52 isoform subunit of NF-kB predominates the interaction with the kB element in the hPim-2 promoter in B-CLL cells, as compared to the p50 isoform observed in control B-cells. To determine whether these interactions are transcriptionaly significant, we fused the luciferase reporter gene to various promoter fragments, and monitored luciferase expression in-vitroafter incubation with either B-CLL or normal B-cell extracts. Luciferase expression was consistently higher when Oct element-containing fragment was incubated with B-CLL cell extracts. Together, these results suggest that the upregulation of hPim-2 in B-CLL is due to enhanced expression and transcriptional activity of the Oct-1+2 and Bob-1 complex and that it might synergistically act with the p52 containing NF-kB transcription factor.
- Published
- 2004
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.