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Biomedical subjects

A Eldor

Publications and source records attributed to A Eldor.

At least 55 records · Page 3Linked to original sources
PubMed1999

Increased frequency of genetic thrombophilia in women with complications of pregnancy.

BACKGROUND: Obstetrical complications such as severe preeclampsia, abruptio placentae, fetal growth retardation, and stillbirth are associated with intervillous or spiral-artery thrombosis and inadequate placental perfusion. Whether these complications are associated with an increased frequency of thrombophilic mutations is not known. METHODS: We studied 110 women who had one of the above-mentioned obstetrical complications and 110 women who had one or more normal pregnancies. The women were tested several days after delivery for the mutation of guanine to adenine at nucleotide 1691 [corrected] in the factor V gene (factor V Leiden), the mutation of cytosine to thymine at nucleotide 677 in the gene encoding methylenetetrahydrofolate reductase, and the mutation of guanine to adenine at nucleotide 20210 in the prothrombin gene. Two to three months after delivery the women were tested for deficiency of protein C, protein S, or antithrombin III and for the presence of anticardiolipin antibodies. RESULTS: The mutation at nucleotide 1691 [corrected] in the factor V gene was detected in 22 of the women with obstetrical complications and in 7 of the women with normal pregnancies (20 percent and 6 percent, respectively; P=0.003). Twenty-four women with complications, as compared with nine women without complications, were homozygous for the C677T mutation in the gene encoding methylenetetrahydrofolate reductase (22 percent and 8 percent, respectively; P=0.005). The G20210A mutation in the prothrombin gene was found in 11 women with complications as compared with 3 women without complications (10 percent and 3 percent, respectively; P=0.03). Overall, 57 women with obstetrical complications had a thrombophilic mutation, as compared with 19 women with normal pregnancies (52 percent and 17 percent, respectively; P<0.001). Deficiency of protein S, protein C, or antithrombin III or anticardiolipin antibodies were detected in an additional 14 women with complications, as compared with 1 woman with a normal pregnancy (13 percent and 1 percent, respectively; P<0.001). CONCLUSIONS: Women with serious obstetrical complications have an increased incidence of mutations predisposing them to thrombosis and other inherited and acquired forms of thrombophilia.

Abruptio Placentae↗
PubMed1999

Monoclonal anti-endothelial cell antibodies from a patient with Takayasu arteritis activate endothelial cells from large vessels.

OBJECTIVE: To create monoclonal anti-endothelial cell antibodies (mAECA) from a patient with Takayasu arteritis to evaluate their ability to activate human umbilical vein endothelial cells (HUVEC), and to characterize the mechanism of EC activation. METHODS: A panel of mAECA was generated from peripheral blood lymphocytes of a patient with Takayasu arteritis, using Epstein-Barr virus transformation. Activity against macrovascular EC (HUVEC) and microvascular EC (human bone marrow EC immortalized by SV40) antigens was detected by enzyme-linked immunosorbent assay. Inhibition studies were used to select the monoclonal antibodies (mAECA) which share the same EC epitope binding specificity as the total IgG-AECA from the Takayasu arteritis patient. The binding of the mAECA to human aortic EC was studied by immunohistochemistry. The secretion levels of interleukin-6 (IL-6) and von Willebrand factor (vWF) were determined, to serve as markers for EC activation. The activated EC were examined for the adherence of a monocytic cell line (U937), as well as for expression of vascular cell adhesion molecule 1, intercellular adhesion molecule 1, and E-selectin. In addition, nuclear extracts of the mAECA-treated EC were analyzed for the induction of translocation of nuclear factor kappaB (NF-kappaB), using a specific NF-kappaB oligoprobe in an electrophoretic mobility shift assay. RESULTS: Six mAECA were selected, the mixture of which produced 100% inhibition of binding of the original IgG (from the patient with Takayasu arteritis) to HUVEC. All mAECA possessed high activity against macrovascular EC, but none had significant antimicrovascular EC activity. The mAECA, but not normal human IgG, had anti-human aortic EC activity. Four of the 6 mAECA activated EC, manifested by increased IL-6 and vWF secretion. The 4 mAECA induced EC expression of adhesion molecules and increased adhesion of U937 monocytic cells to EC. In addition, these mAECA stimulated the nuclear translocation of the NF-kappaB transcription factor. CONCLUSION: Our findings suggest that AECA may directly stimulate EC in Takayasu arteritis through elevation of adhesion molecule expression associated with NF-kappaB activation and adhesion of monocytes, and may therefore play a pathogenic role in the development of the vasculopathy in Takayasu arteritis.

Adult↗
PubMed1999

Increased expression of the CD11b/CD18 antigen on the surface of peripheral white blood cells in patients with ischemic heart disease: further evidence for smoldering inflammation in patients with atherosclerosis.

BACKGROUND: This study examined the availability of the CD11b/CD18 and CD62L antigens on the surface of peripheral blood leukocytes in patients with ischemic heart disease. METHODS AND RESULTS: The study population included 45 patients with angiographically documented ischemic heart disease admitted to our department of internal medicine and the cardiology department during 1 month (December 1997). Sixty-six healthy members of the hospital medical staff served as control subjects. Another 39 post-trauma patients who were admitted to the emergency room were also evaluated. Patients with ischemic heart disease had significantly (P <.002) higher concentrations of CD11b/CD18 antigen on the surface of their polymorphonuclear leukocytes and monocytes (mean fluorescence intensity of 203 +/- 81 and 261 +/- 75, respectively) compared with the control group (mean fluorescence intensity 158 +/- 68 and 211 +/- 74, respectively) and to the group of patients with acute stress (mean fluorescence intensity of 146 +/- 70 and 200 +/- 22, respectively). CONCLUSIONS: The presence of increased concentration of CD11b/CD18 suggests that circulating leukocytes are activated in patients with ischemic heart disease. This activation probably reflects the presence of an inflammatory response involving the atherosclerotic lesion and is not merely a result of acute stress.

Aged↗
PubMed1999

Placing the newborn on the maternal abdomen after delivery increases the volume and CD34 cell content in the umbilical cord blood collected: an old maneuver with new applications.

OBJECTIVE: Our purpose was to increase the number of the progenitor cells in umbilical cord blood collected for transplantation. STUDY DESIGN: We randomly assessed the effect of "upper" and "lower" positions of the newborn on the volume and progenitor cell (CD34(+)) content of the umbilical cord blood collected from 49 healthy, vaginally delivered, term neonates. RESULTS: Twenty-two collections were performed in the "upper" and 27 in the "lower" position. The volume of umbilical cord blood obtained in the "upper" position was 108.1 +/- 19.1 mL compared with 42.6 +/- 19.5 mL in the "lower" position (P <.0001). Mononuclear cell separation revealed significantly higher numbers of cells in umbilical cord blood obtained in the "upper" group (P <.01). Although the percentage of CD34(+) cells was comparable, the absolute number of CD34(+) cells was significantly higher in the "upper" group because of the larger volume collected (P <.02). At 24 hours after delivery the hemoglobin levels were not significantly different between newborns of the 2 groups. CONCLUSIONS: Placing the newborn on the maternal abdomen after delivery and before cord clamping may significantly increase the volume of umbilical cord blood collected and therefore the CD34(+) counts that improve transplantation success without placing the mother or the newborn at risk.

Antigens, CD34↗
PubMed1999

Retinal vein occlusion associated with methylenetetrahydrofolate reductase mutation.

OBJECTIVE: To report on the occurrence of methylenetetrahydrofolate reductase (MTHFR) deficiency in patients with retinal vein occlusion (RVO). DESIGN: Prospective case series PARTICIPANTS: Fifty-nine consecutive patients with newly diagnosed RVO seen at the Retina Unit in the Tel Aviv Medical Center during 1997. METHODS/TESTING: Interviews and multiple blood analyses were done. Data were compared to the reported incidence of MTHFR deficiency in the Israeli population at large. RESULTS: Twenty-six patients (44.1%) were heterozygotes and 11 (18.6%) were homozygotes for 677C-T mutation in MTHFR. The MTHFR 677C-T homozygosity was documented as being present in 10.4% of healthy individuals in the Israeli population. The difference in homozygosity was found to be statistically significant (P = 0.038). CONCLUSIONS: Retinal vein occlusion may be associated with a mutation in MTHFR.

Adult↗
PubMed1999

A chronic hypercoagulable state in patients with beta-thalassaemia major is already present in childhood.

A higher than normal incidence of thromboembolic events has been observed in adult patients with beta-thalassaemia major (TM) and certain haemostatic anomalies found in these patients suggest the existence of a chronic hypercoagulable state. Thalassaemic red blood cells (RBC) were demonstrated to facilitate thrombin formation due to altered asymmetry of the membrane phospholipids with enhanced exposure of phosphatidylserine. Since RBC anomalies exist in thalassaemia from the first months of life, we studied markers of hypercoagulability and thrombophilia in 36 adult patients (range 19-38 years) and 26 children (range 2-18 years) with beta-TM. All the patients were in steady state and none had experienced clinical signs or symptoms of thrombosis. Highly elevated urinary levels of 11-dehydro-thromboxane B2 and significantly elevated plasma levels of thrombin-antithrombin III (TAT) complexes were observed to the same extent in TM children and adults. The levels of factor II were decreased while factors V, VII + X and plasminogen were within the normal range. The natural coagulation inhibitors, protein C (PC) and protein S (PS) were significantly decreased in all TM patients investigated, regardless of age, but the PS binding protein (C4bBP) and antithrombin III levels were normal. The frequency of other thrombophilic mutations was not increased. Thus, a chronic hypercoagulable state already exists in thalassaemia in childhood and may contribute to the cardiac and pulmonary anomalies and the thrombotic events which occur later.

Adolescent↗
PubMed1999

Structural roles of acetylcholinesterase variants in biology and pathology.

Apart from its catalytic function in hydrolyzing acetylcholine, acetylcholinesterase (AChE) affects cell proliferation, differentiation and responses to various insults, including stress. These responses are at least in part specific to the three C-terminal variants of AChE which are produced by alternative splicing of the single ACHE gene. 'Synaptic' AChE-S constitutes the principal multimeric enzyme in brain and muscle; soluble, monomeric 'readthrough' AChE-R appears in embryonic and tumor cells and is induced under psychological, chemical and physical stress; and glypiated dimers of erythrocytic AChE-E associate with red blood cell membranes. We postulate that the homology of AChE to the cell adhesion proteins, gliotactin, glutactin and the neurexins, which have more established functions in nervous system development, is the basis of its morphogenic functions. Competition between AChE variants and their homologs on interactions with the corresponding protein partners would inevitably modify cellular signaling. This can explain why AChE-S exerts process extension from cultured amphibian, avian and mammalian glia and neurons in a manner that is C-terminus-dependent, refractory to several active site inhibitors and, in certain cases, redundant to the function of AChE-like proteins. Structural functions of AChE variants can explain their proliferative and developmental roles in blood, bone, retinal and neuronal cells. Moreover, the association of AChE excess with amyloid plaques in the degenerating human brain and with progressive cognitive and neuromotor deficiencies observed in AChE-transgenic animal models most likely reflects the combined contributions of catalytic and structural roles.

Acetylcholinesterase↗
PubMed1999

Human osteogenesis involves differentiation-dependent increases in the morphogenically active 3' alternative splicing variant of acetylcholinesterase.

The extended human acetylcholinesterase (AChE) promoter contains many binding sites for osteogenic factors, including 1,25-(OH)2 vitamin D3 and 17beta-estradiol. In differentiating osteosarcoma Saos-2 cells, both of these factors enhanced transcription of the AChE mRNA variant 3' terminated with exon 6 (E6-AChE mRNA), which encodes the catalytically and morphogenically active E6-AChE isoform. In contrast, antisense oligodeoxynucleotide suppression of E6-AChE mRNA expression increased Saos-2 proliferation in a dose- and sequence-dependent manner. The antisense mechanism of action was most likely mediated by mRNA destruction or translational arrest, as cytochemical staining revealed reduction in AChE gene expression. In vivo, we found that E6-AChE mRNA levels rose following midgestation in normally differentiating, postproliferative fetal chondrocytes but not in the osteogenically impaired chondrocytes of dwarf fetuses with thanatophoric dysplasia. Taken together, these findings suggest morphogenic involvement of E6-AChE in the proliferation-differentiation balance characteristic of human osteogenesis.

Acetylcholinesterase↗
PubMed1999

Applying risk assessment models in non-surgical patients: effective risk stratification.

Pulmonary embolism and deep vein thrombosis are serious complications of non-surgical patients, but scarcity of data documenting prophylaxis means antithrombotic therapy is rarely used. Prediction of risk is complicated by the variation in the medical conditions associated with venous thromboembolism (VTE), and lack of data defining risk in different groups. Accurate risk assessment is further confounded by inherited or acquired factors for VTE, additional risk due to medical interventions, and interactions between risk factors. Acquired and inherited risk factors may underlie thromboembolic complications in a range of conditions, including pregnancy, ischaemic stroke, myocardial infarction and cancer. Risk stratification may be feasible in non-surgical patients by considering individual risk factors and their cumulative effects. Current risk assessment models require expansion and modification to reflect emerging evidence in the non-surgical field. A large on-going study of prophylaxis with low-molecular-weight heparin in non-surgical patients will clarify our understanding of the components of risk, and assist in developing therapy recommendations.

Drug-Related Side Effects and Adverse Reactions↗
PubMed1999

Bleeding tendency: a practical approach in dentistry.

The dental profession faces the problems of exaggerated bleeding on a daily basis. The hemostatic, as well as the fibrinolytic processes are better understood today, and the dentist should be familiar with them. The activation of coagulation factors and their clinical expression in the circulation are both described. The most frequently used blood coagulation tests are explained. Antithrombotic medications are frequently used and their implications in dentistry are accentuated. Protocols of prevention and treatment of exaggerated bleeding following dental procedures are included. Among them, the transfusion of clotting factors and the administration of antifibrinolytic medications (tranexamic acid) are recommended for both congenital or acquired bleeding tendencies.

Anticoagulants↗
PubMed1999

A mouse model for heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) occurs in 1% to 3% of patients receiving heparin and results from the development of antibodies that recognize heparin-platelet factor 4 (H-PF4) complexes that form on the surface of activated platelets and on the vascular endothelium. With the aim of studying the pathogenic importance of these anti-H-PF4 antibodies in vivo, we attempted to create an animal model of HIT. Such a model was produced by immunization of naive mice with affinity-purified IgG anti-H-PF4 antibodies from two patients with HIT. The immunized mice developed specific antibodies (anti-idiotypic) against the human anti-H-PF4 antibodies and 2 months later, anti-anti-idiotypic antibodies appeared, which functionally resembled the human HIT antibody. Indeed, when the animals bearing anti-anti-idiotypic antibodies were injected with heparin for 4 days, a significant decrease in their platelet counts was observed; however, heparin treatment was not associated with thrombosis in any of the immunized mice. Similar to the observation in HIT patients, injections of equivalent doses of low-molecular-weight (LMW) heparin to the immunized animals did not induce thrombocytopenia. The results of this study support the importance of anti-H-PF4 antibodies in the pathogenesis of HIT. The mouse HIT model may provide a convenient system for studies on the immunoregulation of anti-H-PF4 expression and for evaluation of potential therapeutic modalities.

Animals↗
PubMed1998

Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases.

Myeloablative conditioning associated with hazardous immediate and late complications is considered as a mandatory first step in preparation for allogeneic blood or marrow transplantation (allogeneic BMT) for the treatment of malignant hematologic disorders and genetic diseases. Immune-mediated graft-versus-leukemia (GVL) effects constitute the major benefit of allogeneic BMT. Therefore, we have introduced the use of relatively nonmyeloablative conditioning before allogeneic BMT aiming for establishing host-versus-graft tolerance for engraftment of donor immunohematopoietic cells for induction of GVL effects to displace residual malignant or genetically abnormal host cells. Our preliminary data in 26 patients with standard indications for allogeneic BMT, including acute leukemia (n = 10); chronic leukemia (n = 8), non-Hodgkin's lymphoma (n = 2), myelodysplastic syndrome (n = 1), multiple myeloma (n = 1), and genetic diseases (n = 4) suggest that nonmyeloablative conditioning including fludarabine, anti-T-lymphocyte globulin, and low-dose busulfan (8 mg/kg) is extremely well tolerated, with no severe procedure-related toxicity. Granulocyte colony-stimulating factor mobilized blood stem cell transplantation with standard dose of cyclosporin A as the sole anti-graft-versus-host disease (GVHD) prophylaxis resulted in stable partial (n = 9) or complete (n = 17) chimerism. In 9 patients absolute neutrophil count (ANC) did not decrease to below 0.1 x 10(9)/L whereas 2 patients never experienced ANC < 0.5 x 10(9)/L. ANC > or = 0.5 x 10(9)/L was accomplished within 10 to 32 (median, 15) days. Platelet counts did not decrease to below 20 x 10(9)/L in 4 patients requiring no platelet support at all; overall platelet counts > 20 x 10(9)/L were achieved within 0 to 35 (median 12) days. Fourteen patients experienced no GVHD at all; severe GVHD (grades 3 and 4) was the single major complication and the cause of death in 4 patients, occurring after early discontinuation of cyclosporine A. Relapse was reversed by allogeneic cell therapy in 2/3 cases, currently with no residual host DNA (male) by cytogenetic analysis and polymerase chain reaction. To date, with an observation period extending over 1 year (median 8 months), 22 of 26 patients (85%) treated by allogeneic nonmyeloablative stem cell transplantation are alive, and 21 (81%) are disease-free. The actuarial probability of disease-free survival at 14 months is 77.5% (95% confidence interval, 53% to 90%). Successful eradication of malignant and genetically abnormal host hematopoietic cells by allogeneic nonmyeloablative stem cell transplantation represents a potential new approach for safer treatment of a large variety of clinical syndromes with an indication for allogeneic BMT. Transient mixed chimerism which may protect the host from severe acute GVHD may be successfully reversed postallogeneic BMT with graded increments of donor lymphocyte infusions, thus resulting in eradication of malignant or genetically abnormal progenitor cells of host origin.

Adolescent↗
PubMed1998

Immune thrombocytopenic purpura in adults: clinical aspects.

Immune thrombocytopenic purpura (ITP) is a relatively common immune-mediated disorder characterized by thrombocytopenia due to clearance of opsonized platelets by the reticuloendothelial system. The acute form, more common in children, is a self-limiting, often post-viral disease. In contrast, the adult form is typically a chronic disorder, which initially responds to corticosteroids. Splenectomy offers a 70% chance of cure. Major progress has been achieved in the elucidation of the immune pathology in ITP, and we review contemporary advances in the treatment of chronic ITP. Practical guidelines for the diagnosis and treatment of various aspects of ITP were established in 1996 by the American Society of Hematology. Since these recommendations will most probably substantially influence patient care, they are discussed in detail. Human immunodeficiency virus (HIV)-associated ITP is a common problem in countries with a high prevalence of HIV infection. The pathogenesis of this subtype probably differs from that of classic ITP, and is considered separately.

Adult↗
PubMed1998

Thrombotic thrombocytopenic purpura: diagnosis, pathogenesis and modern therapy.

Thrombotic thrombocytopenic purpura (TTP) is an uncommon multisystem disorder, sometimes associated with predisposing conditions such as pregnancy, cancer, exposure to certain drugs, bone marrow transplantation and HIV-1 infection. An abnormal interaction between the vascular endothelium and platelets which occurs in certain organs leads to thrombosis, endothelial proliferation, minimal inflammation and micro-angiopathic haemolysis. Recent studies suggest that endothelial cell perturbation and apoptosis caused by an as yet unknown plasma factor(s) may lead to the release of abnormal von Willebrand factor which facilitates the deposition of platelet microthrombi. Exchange transfusions of plasma or plasma-cryosupernatant remain the cornerstone of the treatment of TTP along with corticosteroids, platelet inhibitor drugs, vincristine and splenectomy. In most cases remissions can be attained, and cures are now common-although approximately one-half of the patients will relapse. While relapses are usually milder, they still carry a significant mortality and preventive therapies are not always effective.

Apoptosis↗
PubMed1998

High-dose intravenous gamma-globulins for heparin-induced thrombocytopenia: a prompt response.

Heparin-induced thrombocytopenia (HIT) is a common drug induced autoimmune condition. The thrombocytopenia is caused in most cases by an antibody directed against the complex PF4/heparin. Recently, we have induced an experimental model of HIT by idiotypic manipulation. To confirm further the idiotypic involvement of HIT, we have treated successfully three patients with HIT with high-dose intravenous gamma-globulin (IVIG). Our three patients joint other two cases previously reported who were treated with IVIG and point to the efficacy of this type of therapy with minimal side effects. IVIG suppression of the anti-PF4/heparin autoantibody may support the idiotypic etiology of HIT.

Aged↗
PubMed1998

Down-regulation of the CD62L antigen as a possible mechanism for neutrophilia during inflammation.

The expressions of both the CD11b/CD18 and CD62L (L-selectin) antigens as well as the absolute number of white blood cells in the peripheral circulating pool of blood in 116 patients with various inflammatory conditions were determined. A highly significant (P<0.0001) negative correlation (r = -0.57) was noted between the absolute number of peripheral blood polymorphonuclear leucocytes and the expression of the CD62L antigen on their surface. In view of the role of CD62L antigen in the rolling of leucocytes along endothelial cells in the microvasculature, its down-regulation might explain, at least in part, the demargination and appearance of neutrophilia during inflammation.

CD18 Antigens↗