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Abdulgabar Salama

Publications and source records attributed to Abdulgabar Salama.

At least 19 recordsLinked to original sources
PubMed2006

Detailed analysis of the variability of peptidylarginine deiminase type 4 in German patients with rheumatoid arthritis: a case-control study.

Peptidylarginine deiminase type 4 (PADI4) genotypes were shown to influence susceptibility to rheumatoid arthritis (RA) in the Japanese population. Such an association could not previously be confirmed in different European populations. In the present study, we analysed exons 2-4 of PADI4 in 102 German RA patients and 102 healthy individuals to study the influence of PADI4 variability on RA susceptibility by means of haplotype-specific DNA sequencing. Analyses of the influence of PADI4 and HLA-DRB1 genotypes on disease activity and on levels of anti-cyclic citrullinated peptide antibodies were performed. Comparing the frequencies of PADI4 haplotype 4 (padi4_89*G, padi4_90*T, padi4_92*G, padi4_94*T, padi4_104*C, padi4_95*G, padi4_96*T) (patients, 14.7%; controls, 7.8%; odds ratio = 2.0, 95% confidence interval = 1.1-3.8) and carriers of this haplotype (patients, 27.5%; controls, 13.7%; odds ratio = 2.4, 95% confidence interval = 1.2-4.8), a significant positive association of PADI4 haplotype 4 with RA could be demonstrated. Other PADI4 haplotypes did not differ significantly between patients and controls. Regarding the individual PADI4 variants, padi4_89 (A-->G), padi4_90 (C-->T), and padi4_94 (C-->T) were significantly associated with RA (patients, 49.5%; controls, 38.7%; odds ratio = 1.6, 95% confidence interval = 1.1-2.3). Considering novel PADI4 variants located in or near to exons 2, 3, and 4, no quantitative or qualitative differences between RA patients (8.8%) and healthy controls (10.8%) could be demonstrated. While the PADI4 genotype did not influence disease activity and the anti-cyclic citrullinated peptide antibody level, the presence of the HLA-DRB1 shared epitope was significantly associated with higher anti-cyclic citrullinated peptide antibody levels (P = 0.033). The results of this small case-control study support the hypothesis that variability of the PADI4 gene may influence susceptibility to RA in the German population. Quantitative or qualitative differences in previously undefined PADI4 variants between patients and controls could not be demonstrated.

Adolescent↗
PubMed2006

Misdiagnosis in patients with diclofenac-induced hemolysis: new cases and a concise review.

Diclofenac has been implicated in many cases of life-threatening immune hemolytic anemia (IHA). Nevertheless, confusion still occurs at the bedside and in the laboratory. Herein we report nine new patients and summarize all published cases (total, n = 61). Direct and indirect antiglobulin tests were performed according to standard procedures. Tests for drug-dependent antibodies were performed in the presence and absence of the target drugs and their ex vivo antigens (in the urine of patients treated with the drug). Diclofenac- and/or ex-vivo-antigen-dependent red cell antibodies were detected in all new cases. We identified nine new cases with diclofenac-dependent IHA. All cases were initially suspected to have an abdominal illness and/or autoimmune hemolytic anemia of warm type. Acute renal failure was present in three of the 9 new patients and in 20 of 37 published patients. Seven of the 46 patients died (15%), and clinical information is lacking in 15 other published cases. Diclofenac-dependent and/or ex-vivo-antigen-dependent IHA should always be considered when a patient on diclofenac develops acute renal failure and/or IHA.

Acute Kidney Injury↗
PubMed2005

Hemoglobin screening in prospective blood donors: comparison of different blood samples and different quantitative methods.

Portable photometers are increasingly used for hemoglobin screening in blood centers. In a total of 500 unselected prospective blood donors, venous hemoglobin concentrations were measured using a hematology analyzer, and fingerstick hemoglobin concentrations were measured on both a HemoCue B and a Biotest hemoglobin photometer. In 100 of the donors, earstick hemoglobin levels were also measured on the HemoCue system. The mean hemoglobin levels in the fingerstick samples were slightly higher than those in the venous samples. The deviation exceeded the limit of +/-10g l(-1) in 9% of samples tested by HemoCue and in 20% of those investigated by Biotest. The use of earstick samples led to considerable overestimation of the actual hemoglobin concentration.

Blood Donors↗
PubMed2005

Failure of bedside ABO testing is still the most common cause of incorrect blood transfusion in the Barcode era.

BACKGROUND AND OBJECTIVES: ABO-incompatible red blood cell (RBC) transfusions are a major risk in transfusion medicine. Identification of factors leading to this hazard is important to improve transfusion safety. MATERIAL AND METHODS: All consecutive erroneous ABO-incompatible transfusions occurring from January 1997 to December 2004 at the Charité University Hospital in Berlin, Germany were analysed. RESULTS: A total of 343,432 RBC units were transfused, and eight patients erroneously received 13 ABO-incompatible RBC concentrates. The most frequent error was incorrect bedside testing (n=7). Intensive care treatment was required in two cases, but there were no fatal mistransfusions. Four patients had no or only mild reactions. CONCLUSION: Mistransfusions are still a considerable risk in transfusion medicine despite quality control systems and electronic data processing. An increase in transfusion safety may require the introduction of further systems, e.g. radio-frequency identification (RFID) tags.

ABO Blood-Group System↗
PubMed2005

The alpha4beta1 and alpha5beta1 integrins mediate engraftment of granulocyte-colony-stimulating factor-mobilized human hematopoietic progenitor cells.

BACKGROUND: The alpha4beta1 and alpha5beta1 integrins are major adhesion molecules of murine and human hematopoietic progenitor cells. Granulocyte-colony-stimulating factor (G-CSF)-mobilized peripheral blood progenitor cells (PBPCs) are the most important source for clinical hematopoietic cell transplantation today. The contribution of alpha4beta1 and alpha5beta1 integrins to homing of PBPCs has not been studied yet. STUDY DESIGN AND METHODS: The expression of alpha4beta1 and alpha5beta1 integrins on purified human PBPCs was analyzed. Integrin function in adhesion to recombinant fibronectin and migration on fibronectin-coated transwells was assessed with fragments combining different adhesion domains and function-blocking antibodies. Finally, the function of those integrins in a transplantation model was investigated with repopulating cells of nonobese diabetic/severe combined immune-deficient (NOD/SCID) mice. RESULTS: More than 90 percent of all purified peripheral blood CD34+ cells express alpha4beta1 integrins, whereas only 10 to 15 percent express alpha5beta1. The alpha4beta1 integrin alone influences adhesion whereas alpha4beta1 and alpha5beta1 both mediate chemotaxis of clonogenic CD34+ progenitor cells on recombinant fibronectin. Importantly, antibodies against the integrins alpha4beta1 and alpha5beta1 independently reduce the repopulation of NOD/SCID mouse marrow after transplantation of human peripheral blood CD34+ cells. CONCLUSIONS: Alpha4beta1 and alpha5beta1 integrins are functional and critical adhesion receptors expressed on G-CSF-mobilized CD34+ hematopoietic blood progenitor cells with repopulating capacity mediating engraftment after transplantation.

Animals↗
PubMed2005

Rapid identification of iron deficiency in blood donors with red cell indexes provided by Advia 120.

BACKGROUND: A new generation of automated hematology analyzers allows the rapid determination of various red cell (RBC) indexes, including the percentage of hypochromic mature RBCs (HYPOm) and the hemoglobin (Hb) content of reticulocytes (CHr). These indexes have not yet been validated as measures for the detection of iron deficiency in blood donors. STUDY DESIGN AND METHODS: Iron status was evaluated in a total of 1142 unselected prospective blood donors based on measurement of serum ferritin, soluble transferrin receptor, and Hb compared to RBC indexes provided by an automated hematology analyzer (Advia 120, Bayer HealthCare) including HYPOm and CHr. RESULTS: Assuming that the most precise measure for body iron storage is related to the logarithm of the ratio of soluble transferrin receptor to ferritin, the sensitivity of ferritin for the diagnosis of iron depletion was 89 percent compared to 57 percent for HYPOm and CHr, respectively, to 69 percent for the combination of both RBC indexes, and to 26 percent for Hb concentration. CONCLUSION: The RBC indexes HYPOm und CHr are significantly better screening measures for identification of iron depletion in blood donors than Hb.

Adolescent↗
PubMed2005

After major ABO-mismatched allogeneic hematopoietic progenitor cell transplantation, erythroid engraftment occurs later in patients with donor blood group A than donor blood group B.

BACKGROUND: Isohemagglutinins directed against the donor blood group frequently delay erythroid engraftment after major ABO-mismatched allogeneic hematopoietic progenitor cell transplantation (HPCT). Graft-versus-host reactions are capable of accelerating the clearance of isohemagglutinins. Whether immunogenicity of the A- and B-antigen is important in this process is unknown. PATIENTS AND METHODS: Data of 807 patients from three centers were screened for patients with major or bidirectionally ABO-mismatched donors. Clinical data and red blood cell (RBC) transfusion support were analyzed retrospectively. RESULTS: A total of 158 patients with major or bidirectionally mismatched donors were identified. After major mismatched HPCT, patients with anti-A directed against the donor blood group required RBC transfusion support for a median of 109 days (range, 0-324 days) compared to 21 days (range, 2-98 days) for patients with anti-B directed against donor blood group (log-rank test, p = 0.0001). Other risk factors associated with prolonged RBC transfusion support in univariate analysis were age (p = 0.024), cytomegalovirus infection (p = 0.016), hemolytic anemia (p = 0.027), and chronic bleeding disorders (p = 0.038). The independent influence of donor blood group and recipient age were confirmed in a multivariate analysis. CONCLUSION: These results indicate that the immunogenicity of the ABO antigen plays an important role for the kinetics of erythroid engraftment after ABO-mismatched HPCT.

ABO Blood-Group System↗
PubMed2005

Oxaliplatin-induced immune pancytopenia.

BACKGROUND: Oxaliplatin, a third-generation platinum compound, has been implicated in isolated cases of immune hemolytic anemia and/or immune thrombocytopenia. The first case of severe immune pancytopenia related to oxaliplatin is described. PATIENT AND METHODS: A 79-year-old woman with colorectal cancer was initially treated with 5-fluorouracil and she later received oxaliplatin and leucovorin every 2 to 4 weeks. During the 15th and 17th cycles of chemotherapy she developed thrombocytopenia, hemolysis, and neutropenia. No problems occurred during the 16th cycle without oxaliplatin. Serologic testing including detection of drug-dependent antibodies and autoantibodies was performed with standard techniques. RESULTS: Serologic findings included a positive immunoglobulin G direct antiglobulin test; nonreactive red blood cell (RBC) eluates; platelet (PLT)-bound antibodies to glycophorin (GP) IIb-IIIa, GPIb-IX, and GPIa-IIa; and oxaliplatin-dependent antibodies to PLTs, RBCs, and neutrophils. CONCLUSION: Oxaliplatin may lead to the production of ddabs to RBCs, PLTs, and neutrophils. Thus the risk of immune cytopenias should always be considered in patients treated with oxaliplatin.

Aged↗
PubMed2004

Marburg I polymorphism of factor VII-activating protease is associated with idiopathic venous thromboembolism.

The factor VII-activating protease (FSAP) variant Marburg I is known to attenuate the profibrinolytic system in vitro and was recently shown to be a significant predictor for the evolution and progression of carotid stenosis. The objective of this case-control study was to assess FSAP Marburg I's role in the occurrence of venous thromboembolism (VTE). The frequency of FSAP Marburg I was significantly increased in patients with a history of VTE (17 of 213 patients, 8.0%, P = .014) or idiopathic VTE (12 of 103 patients, 11.7%, P = .002) compared to healthy controls (5 of 213 controls, 2.3%). Logistic regression analysis confirmed FSAP Marburg I to be an independent risk factor for VTE (odds ratio, 3.5; 95% confidence interval [CI], 1.2-10.0) and idiopathic VTE (odds ratio, 6.2; 95% CI, 2.0-18.9).

Adolescent↗
PubMed2004

Mesenchymal stem cell content of human vertebral bone marrow.

Mesenchymal stem cells (MSCs) are capable of down-regulating alloimmune responses and promoting the engraftment of hematopoietic stem cells. MSCs may therefore be suitable for improving donor-specific tolerance induction in solid-organ transplantation. Cells from cadaveric vertebral bone marrow (V-BM), aspirated iliac crest-BM, and peripheral blood progenitor cells were compared. Cells were characterized by flow cytometry and colony assays. MSCs generated from V-BM were assayed for differentiation capacity and immunomodulatory function. A median 5.7 x 10(8) nucleated cells (NCs) were recovered per vertebral body. The mesenchymal progenitor, colony-forming unit-fibroblast, frequency in V-BM (11.6/10(5) NC, range: 6.0-20.0) was considerably higher than in iliac crest-BM (1.4/10(5) NC, range: 0.4-2.6) and peripheral blood progenitor cells (not detectable). MSC generated from V-BM had the typical MSC phenotype (CD105(pos)CD73(pos)CD45(neg)CD34(neg)), displayed multilineage differentiation potential, and suppressed alloreactivity in mixed lymphocyte reactions. V-BM may be an excellent source for MSC cotransplantation approaches.

Antigens, CD↗
PubMed2004

High variability of peptidylarginine deiminase 4 (PADI4) in a healthy white population: characterization of six new variants of PADI4 exons 2-4 by a novel haplotype-specific sequencing-based approach.

Seven single nucleotide polymorphisms (SNPs) of the peptidylarginine deiminase 4 (PADI4) gene have recently been reported to be strongly associated with rheumatoid arthritis in Japanese individuals. These SNPs are located in or close to exons 2-4 of PADI4 and are organized in at least four different haplotypes. However, a detailed sequencing-based characterization of the PADI4 gene in other populations is still lacking. We therefore analyzed exons 2-4 of the PADI4 gene in 102 healthy white Germans individuals by DNA sequencing and characterized new variants and haplotypes by a novel haplotype-specific sequencing-based approach. The haplotypes 2/3 (padi4_89*G, padi4_90*T, padi4_92*G, padi4_94*T, padi4_104*T, padi4_95*C, padi4_96*C), and haplotype 4 (padi4_89*G, padi4_90*T, padi4_92*G, padi4_94*T, padi4_104*C, padi4_95*G, padi4_96*T) conferring susceptibility to rheumatoid arthritis were detected at frequencies of 30.9% and 7.8%, respectively. In addition, three novel coding SNPs in exons 2, 3, and 4, and three SNPs in introns 2 and 3 located near the exon-intron boundaries were identified in 11 individuals (10.8%). The so-called nonsusceptibility haplotype 1 (padi4_89*A, padi4_90*C, padi4_92*C, padi4_94*C, padi4_104*C, padi4_95*G, padi4_96*T) occurred at a frequency of 58.3%. Additionally, we identified a closely related novel haplotype, haplotype 1B (2.9%), that differs from haplotype 1 only by padi4_92*G/padi4_96*C. This haplotype was not described in the Japanese population. Our results indicate that the PADI4 gene exhibits a remarkable variability and a rather complex haplotypic organization. Further studies on disease association of PADI4 should be performed by haplotype-specific sequencing-based approaches to identify the exact genotype of the PADI4 fragment of interest.

Exons↗
PubMed2004

Histone deacetylase inhibition improves dendritic cell differentiation of leukemic blasts with AML1-containing fusion proteins.

Recurrent cytogenetic abnormalities in leukemic blasts make these an attractive source for dendritic cells (DC) to induce a leukemia-specific immune response. In this study, three leukemic cell lines were investigated: Kasumi-1 and SKNO-1 (two acute myeloid leukemia (AML) cell lines carrying the (8;21)-chromosomal translocation, resulting in the expression of the leukemia-specific fusion protein AML1-eight-twenty-one) and REH, an acute lymphoblastic leukemia cell line with the (12;21)-chromosomal translocation and expression of translocation ETS-like leukemia-AML1. These fusion proteins are implicated in the pathogenesis of the leukemic state by recruiting corepressors and histone deacetylases (HDAC), which interfere with normal cell differentiation. In vitro generation of DC was achieved using a cytokine cocktail containing tumor necrosis factor alpha, granulocyte macrophage-colony stimulating factor, c-kit ligand, and soluble CD40 ligand; yet, addition of the HDAC inhibitor (Hdi) trichostatin A enhanced DC differentiation with retention of the fusion transcripts. These leukemic DC showed high-level CD83 and human leukocyte antigen (HLA)-DR expression and had a high allostimulatory potential. Only DC generated from these cell lines after Hdi induced blast-specific cytotoxic T cell responses in HLA-A-matched T cells with a cytotoxicity of 42% in parental Kasumi-1 and 83% in parental REH cells, respectively. This model system suggests that the Hdi supports the in vitro differentiation of DC from leukemic blasts with AML1-containing fusion proteins.

Antigens, CD↗
PubMed2004

Flow cytometric detection of complement-activating HLA antibodies.

BACKGROUND: Antibodies to HLA are implicated in allograft rejection; as a consequence, tests to identify them are indicated in organ transplantation. Flow cytometry (FC) may improve the outcome of organ transplantation. Although increasingly used, most of the available FC techniques do not discriminate between complement and noncomplement-activating antibodies. However, the clinical relevance of noncomplement-activating antibodies is controversial. Therefore, many laboratories still use the conventional complement-dependent microlymphocytotoxicity crossmatch (CDC-XM) alone or in combination with FC. METHODS: We describe a novel flow cytometric complement-dependent cytotoxicity crossmatch assay (FC-CDC-XM) that clearly identifies complement-binding HLA antibodies. With the aid of a three-color FACScan flow cytometer with a standard argon ion laser, we used fluorescence-conjugated anti-CD3 for the identification of T lymphocytes, anti-CD19 antibodies for the identification of B lymphocytes, and propidium iodide (PI) for the identification of damaged cells. Fluorescence-conjugated anti-CD3 and anti-CD19 antibodies were detected in the green (FL1) and orange (FL2) ranges of the spectrum. PI fluorescence was measured with the red (FL3) fluorescence channel. Gating of lymphocytes was performed using side scatter versus FL1 or FL2 dot plots for the identification of T and B lymphocytes, respectively. RESULTS: FC-CDC-XM was able to correctly identify all antibodies tested as specific to HLA class I (n = 18) or II (n = 4). CONCLUSIONS: The new FC-CDC-XM is more sensitive and more objective than the standard CDC-XM and can be used for pre- and posttransplant diagnoses and for the detection of other antibody-mediated cytotoxic reactions.

Complement Activation↗
PubMed2004

Universal leukodepletion of blood components results in a significant reduction of febrile non-hemolytic but not allergic transfusion reactions.

BACKGROUND: Universal leukodepletion of blood components to prevent acute non-hemolytic transfusion reactions (NHTRs) is still a subject of debate. PATIENTS AND METHODS: Transfusion-associated NHTRs observed at our hospital in the last 6 years were retrospectively analyzed. Buffy-coat depleted red blood cells (bc-RBCs), and if indicated, leucodepleted post-storage (ld-RBCs) were initially used. In April 1997, universal leukodepletion was implemented at our hospital, and thereafter only prestorage ld-RBCs were used. All platelet concentrates transfused during this time were prestorage filtered single-donor apheresis platelets (SDAPs). RESULTS: A total of 163,090 blood products were transfused from April 1995 to April 2001 (bc-RBC: n=34,040 units; ld-RBC: n=66,967; SDAP: n=14,516; FFP: n=47,567). The number of post-transfusion febrile NHTRs occurring with each blood product was 65 (0.19%) for bc-RBCs, 8 (0.16%) for post-storage ld-RBCs, 16 (0.03%) for prestorage ld-RBCs, 16 (0.11%) for SDAPs, and 10 (0.02%) for FFP. Allergic reactions (n=116) were most frequently observed after SDAP transfusion (0.32%) and occurred at a similarly low rate after transfusion of all other blood components (0.03-0.08%). CONCLUSION: In conclusion, acute NHTRs rarely occur after the use of leukodepleted blood components. Prestorage appears to be more effective than post-storage leukodepletion in preventing febrile reactions following a blood transfusion.

Blood Component Removal↗
PubMed2004

A new strategy for the prevention of IgA anaphylactic transfusion reactions.

BACKGROUND: Management of patients with clinically significant anti-IgA is difficult and unsatisfactory in many aspects. PATIENTS AND METHOD: A 40-year-old man with common variable immunodeficiency had a previous history of anaphylaxis after an intramuscular immunoglobulin administration. His serum contained anti-IgA, and he required immunoglobulins for recurrent infections. RESULTS: The administration of intravenous immunoglobulins (IVIgG) containing less than 0.1 mg per mL IgA led to an anaphylactic reaction after the transfusion of only 2 to 3 mL. The same IVIgG charge was subsequently pretreated with freshly separated autologous plasma and given to the patient on three consecutive days without any reaction (1.25, 10, and 10 g each in 400 mL plasma). Anti-IgA activity did not increase, and the patient was treated again without complications. DISCUSSION: Ex vivo pretreatment of IVIgG preparations with autologous plasma appears to be safe and useful in the management of patients with clinically significant anti-IgA. To achieve a significant IgA blockage, the preparation to be used should not contain large amounts of IgA. CONCLUSION: The strategy described here appears to be safe and may help prevent anaphylaxis in many instances.

Adult↗