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Biomedical subjects

E Prager

Publications and source records attributed to E Prager.

At least 19 recordsLinked to original sources
PubMed2001

Characterization of CDw92 as a member of the choline transporter-like protein family regulated specifically on dendritic cells.

CDw92 is a 70-kDa surface protein broadly expressed on leukocytes and endothelial cells. In this manuscript, we present the molecular cloning of the CDw92 molecule by using a highly efficient retroviral expression cloning system. Sequence analysis of the CDw92 cDNA revealed a length of 2679 bp. The 1959-bp open reading frame encodes a protein of 652 amino acids. Computational analysis of the CDw92 protein sequence indicates 10 transmembrane domains, three potential N-linked glycosylation sites, and an amino acid stretch in the C-terminal region that is related to the immunoreceptor tyrosine-based inhibitory motif. Comparison of the sequence of the CDw92 clone presented in this study with various database entries show that it is a C-terminal variant of human choline transporter-like protein 1, a member of a recently identified family of multitransmembrane surface proteins. Furthermore, we found that CDw92 is stably expressed on monocytes, PBLs, and endothelial cells, as we did not yet find modulation of expression by various stimuli on these cells. In contrast to this factor-independent expression of CDw92, we detected a specific regulation of CDw92 on monocyte-derived dendritic cells (Mo-DCs). Maturation of Mo-DCs by ionomycin or calcium ionophore resulted in down-regulation of CDw92 and incubation of these cells with IL-10 in a specific re-expression. Moreover, targeting of CDw92 on LPS-treated Mo-DCs by CDw92 mAb VIM15b augmented the LPS-induced IL-10 production 2.8-fold. Together, these data suggest a crucial role of the CDw92 protein in the biology and regulation of the function of leukocytes in particular DCs.

Amino Acid Sequence↗
PubMed2001

Induction of hyporesponsiveness and impaired T lymphocyte activation by the CD31 receptor:ligand pathway in T cells.

CD31 is a member of the Ig superfamily expressed on various cell types of the vasculature, including a certain subpopulation of T lymphocytes. Previous reports suggest that interaction of CD31 with its heterophilic ligand on T cells (T cell CD31 ligand) plays a regulatory role in T lymphocyte activation. Here we demonstrate that a soluble rCD31-receptorglobulin (CD31Rg) specifically down-regulated the proliferation of human peripheral blood CD31(-) T lymphocytes stimulated via CD3 and CD28 mAbs. Notably, engagement of the T cell CD31 ligand by CD31Rg during primary stimulation also induced a prolonged unresponsive state in T cells. Retroviral transduction of CD31 into CD31(-) Th clones resulted in a significant inhibition of their proliferative capacity. When cocultured with purified CD31(-) T lymphocytes, irradiated CD31-transduced Th clones counterregulated the CD3/CD28-mediated activation of these cells. Furthermore, primary stimulation in the presence of CD31-transduced Th clones induced a comparable state of hyporesponsiveness in the T cell responders as the soluble CD31Rg. Thus, by counterregulating the activation of cognate T lymphocytes, CD31-expressing T cells might contribute to the establishment and maintenance of peripheral tolerance.

Abatacept↗
PubMed2001

Platelet endothelial cell adhesion molecule-1 and vascular endothelial cadherin cooperatively regulate fibroblast growth factor-induced modulations of adherens junction functions.

Cellular adherens junctions are formed by cadherins linked to proteins of the catenin family. In endothelial cells, not only vascular endothelial cadherin but also platelet endothelial cell adhesion molecule-1 localizes into junctions and associates with beta-catenin. To explore a putative cooperation of platelet endothelial cell adhesion molecule-1 and vascular endothelial cadherin, we analyzed transfectants expressing either platelet endothelial cell adhesion (CD31 cells) or vascular endothelial cadherin (CD144 cells) or both molecules (CD31/CD144 cells), and, for comparison, human umbilical vein endothelial cells. Basic fibroblast growth factor completely dissociated vascular endothelial cadherin/beta-catenin complexes and robustly moved beta-catenin into the nucleus in CD144 cells, whereas in CD31/CD144 cells as well as in human umbilical vein endothelial cells, fibroblast growth factor only partially dissociated the junctional complex followed by a significantly reduced nuclear translocation of beta-catenin. In contrast, in CD31 cells, the subcellular distribution of beta-catenin remained unaffected by fibroblast growth factor. As a functional consequence, fibroblast growth factor induced a complete collapse of the F-actin network in CD144 cells, a limited rearrangement of F-actin fibers in CD31/CD144 cells and no F-actin rearrangement in CD31 cells. We also analyzed the effect of fibroblast growth factor-induced rearrangement of junctions on junction permeability for leukocytes: in line with our observation that vascular endothelial cadherin was required for cells to respond to fibroblast growth factor, only in CD31/CD144 cells, but not in CD31 cells, leukocyte transmigration was significantly enhanced by fibroblast growth factor. In conclusion platelet endothelial cell adhesion molecule-1 cooperates with vascular endothelial cadherin in a mutual fashion; platelet endothelial cell adhesion molecule-1 reduces and temporarily limits fibroblast growth factor-induced dissociation of vascular endothelial cadherin/beta-catenin complexes, but requires vascular endothelial cadherin to control leukocyte transmigration in dependence of fibroblast growth factor.

Adherens Junctions↗
PubMed2001

Pelvic desmoid tumor: threat to mother and fetus.

Desmoid tumors (DTs) are well-recognized extracolonic manifestations of familial adenomatous polyposis. Surgical trauma and hormonal changes during pregnancy have been proposed as etiologic factors. We present a case of a rapidly growing pelvic DT arising from a J-pouch in a 27-year-old pregnant woman status postcolectomy with ileoanal J pouch anastomosis. The tumor interfered with the normal maturation and delivery of the fetus as well as the patient's ability to void or defecate prompting surgical intervention with resection of the tumor and adjacent J pouch at 23 weeks gestation. There are no other reports in the literature of pelvic DT requiring resection during pregnancy. Pelvic DTs in this scenario are potentially fatal to both mother and fetus secondary to uncontrolled bleeding. Surgical intervention should be limited to resection of tumor and when necessary the ileal pouch to minimize bleeding complications.

Adult↗
PubMed1999

T cell activation-associated epitopes of CD147 in regulation of the T cell response, and their definition by antibody affinity and antigen density.

CD147 is a broadly expressed cell surface glycoprotein of the Ig superfamily whose expression is up-regulated upon T cell activation. In order to elucidate a possible role of CD147 in T cell biology, we established 15 specific mAb. Seven distinct epitopes were defined by the mAb panel. Most of the mAb bound only to phytohemagglutinin (PHA)-activated but not resting T cells. We demonstrate that this was not because of true expression of activation-dependent neoepitopes but rather due to bivalent binding of the relatively low-affinity mAb (affinity constant KA values between 2.25 x 10(8) and 7 x 10(9) M-1) to the more densely expressed and/or more clustered CD147 molecules on the activated T cells. In contrast, the mAb with higher affinity (KA > 7 x 10(9) M-1) could stably bind in a monovalent fashion even to the relatively low dense CD147 molecules on resting T cells. This model might more generally explain the nature of 'activation epitopes' described previously in other leukocyte surface molecules. Finally, we provide evidence that induction of ordered dimerization of CD147 by a mAb directed to a unique epitope results in strong inhibition of CD3-mediated T cell activation.

Animals↗
PubMed1999

Gender differences in positive and negative self-assessments of health status in a national epidemiological study of Israeli aged.

The literature in subjective health appraisals frequently notes that elderly women, more so than men, generally experience a lower quality of life in all major indicators (physical health status, functional ability, perceived income adequacy, social contacts, psychological distress, and cognitive ability). The current epidemiological study, of 1,352 reporting Israeli subjects between the ages of 75-94, was undertaken in order to obtain reliable estimates of "poor" and "excellent/good" self assessments of health in a national sample of aged; to identify the most significant correlates of "poor" and "excellent/good" assessments; and to ascertain whether the models of "poor" and "good/excellent" subjective health are different for elderly men and women. While it was found that women indeed rate their health as being poorer than men, of greater theoretical interest was the finding that the pattern of variables predicting to "poor" and "good/excellent" health are different for men and women. The findings point to the fact that the simple health self-evaluation question is not a unitary construct, but rather a complex attitudinal measure which yields different structural and conceptual results when controlling for the subjective health outcome ("poor" or "good/excellent") and when analyzing gender-dichotomized models.

Activities of Daily Living↗
PubMed1998

Human CD38 (ADP-ribosyl cyclase) is a counter-receptor of CD31, an Ig superfamily member.

Human CD38 is a cell surface molecule involved in the regulation of lymphocyte adhesion to endothelial cells. This suggests that HUVEC bear a ligand(s) for CD38 on the cell surface. By means of the mAb Moon-1, which specifically inhibits CD38-mediated cell adhesion, we have identified a trans-membrane 130-kDa molecule acting as a ligand for CD38. Here, we report that the molecule recognized by the Moon-1 mAb is CD31, a member of the Ig superfamily. This conclusion is based on 1) cross-inhibition assays between Moon-1 and reference anti-CD31 mAbs; 2) sequential immunoprecipitation experiments using Moon-1 and known anti-CD31 mAbs, and 3) reactivity of the Moon-1 mAb with CD31 transfectants. Further, CD31 and CD38 cognate interactions were found to modulate heterotypic adhesion as well as to implement cytoplasmic calcium fluxes identical to those obtained by means of agonistic anti-CD38 mAbs. Other effects tested included the synthesis of messages for a panel of cytokines, markedly increased upon receptor-ligand interactions. These results suggest that the interplay between CD38 and its ligand CD31 is an important step in the regulation of cell life and of the migration of leukocytes (and CD38+ cancer cells) through the endothelial cell wall.

ADP-ribosyl Cyclase↗
PubMed1996

Interaction of CD31 with a heterophilic counterreceptor involved in downregulation of human T cell responses.

CD31 is a 130-kD glycoprotein of the immunoglobulin (Ig) superfamily expressed on the surface of endothelial cells, platelets, and several leukocyte subsets. Previous reports indicated that CD31 can mediate intercellular adhesion via both homophilic and heterophilic interaction mechanisms. Using a soluble recombinant CD31-Ig fusion protein (CD31 receptor globulin [Rg]), we demonstrate here that human CD31- T lymphocytes and CD4+CD31- T cell clones express a heterophilic CD31 ligand that is upregulated 18 h after activation. Interaction of CD31Rg with CD31- T helper cell (Th) clones was divalent cation independent but could be blocked by heparin, thus indicating that the CD31 counterreceptor on T cells can be distinguished from the ligands identified on other cell types. Moreover, a single chain protein of 120 kD was precipitated by CD31Rg from the lysates of CD31- Th clones. CD31Rg completely downregulated the proliferative response and cytokine production (interleukin-4, interferon-gamma, and tumor necrosis factor-alpha) of CD31- Th clones when the cells were maximally stimulated via immobilized CD3 monoclonal antibody. These results suggest that interaction of CD31 with a heterophilic counterreceptor on T lymphocytes can interfere with a positive regulatory pathway of T cell activation, or directly signal T cells to downregulate immune function.

Antigens, Differentiation, Myelomonocytic↗
PubMed1995

Granulocyte activation via a binding site near the C-terminal region of complement receptor type 3 alpha-chain (CD11b) potentially involved in intramembrane complex formation with glycosylphosphatidylinositol-anchored Fc gamma RIIIB (CD16) molecules.

We report that engagement of a particular epitope near the C-terminal region of complement receptor type 3 (CR3, CD11b/CD18) alpha-chain with CD11b mAb VIM12 induces granulocyte activation with a rise in cytosolic-free Ca2+, actin polymerization, an up-regulation of CR3 cell surface expression and enhanced adhesiveness. Induction of enhanced adhesiveness and homotypic aggregation of human granulocytes represents an active process. It is temperature and energy dependent, requires divalent cations, and an intact cytoskeleton. The mAb VIM12-induced enhanced adhesiveness seems to be mediated, at least in part, by activated CR3 molecules. It can be significantly inhibited, although not completely abolished, with blocking mAbs against adhesiotopes of CR3. VIM12-induced adhesion could be blocked with the serine/threonine inhibitors okadaic acid and calyculin A and with dibuturyl-cAMP but not with the protein kinase inhibitors herbimycin A and staurosporine. We further present evidence that the particular molecular region of CR3 recognized by mAb VIM12 might be involved in the reported intramembrane sugar-lectin type interaction and complex formation between transmembrane CR3 and glycosylphosphatidylinositol (GPI)-anchored Fc gamma RIIIB (CD16) molecules on human granulocytes. Binding of mAb VIM12 to CR3 on granulocytes enhances the release of GPI-anchored Fc gamma RIIIB molecules from granulocytes upon phosphoinositol-phospholipase C treatment. The sugar preparation N-acetyl-D-glucosamine, previously shown to dissociate CR3-Fc gamma RIIIB complex formation, inhibits mAb VIM12 binding. Engagement of CR3 with mAb VIM12 may thus mimic a biologically relevant intramembrane cooperation between two distinct receptor molecules on human granulocytes.

Actins↗
PubMed1995

Correlates of war-induced stress responses among late middle-aged and elderly Israelis.

Over a period of six weeks in the winter of 1991, Israel was exposed to hostile enemy actions unlike any others in its history. In the Gulf War, civilians were front-line targets for Scud missiles which fell in the heart of the country's most heavily populated areas. One hundred and sixty-four late middle-aged and elderly Israelis were interviewed with respect to their emotional and behavioral reactions. Subjective health, gender, and attribution of meaning were the most significant variables, explaining most of the variance in the two measures of response. Satisfaction with informal network effectiveness was a relatively strong predictor of change in the affective distress variable. Degree of religious commitment and chronological age were weak but significant predictors of affective distress and social interaction distress respectively. Location of residence in relation to the missile impact zone was of no significance in explaining variance in the dependent measures. The findings are discussed in light of the uniquely subjective, interpretive context of stress phenomena, and the need to identify those variables that explain individual differences among older adults in their responses to stress.

Aged↗
PubMed1992

Elderly Israeli Holocaust survivors during the Persian Gulf War: a study of psychological distress.

OBJECTIVE: The aim of the current study was to systematically assess the psychological effects of the Persian Gulf War on a nonclinical group of elderly Israeli civilians with and without a Holocaust background. METHOD: Sixty-one elderly Holocaust survivors and 131 elderly civilians without a Holocaust background completed questionnaires in their homes. Measures included sense of safety, symptoms of psychological distress, and levels of state and trait anxiety. RESULTS: Findings indicate that Holocaust survivors perceived higher levels of danger and reported more symptoms of acute distress than comparison subjects. In addition, they displayed higher levels of both state and trait anxiety. CONCLUSIONS: Findings do not support the notion that prior experience with extreme stress has an inoculating effect that leads to greater resilience in dealing with other forms of stress. On the contrary, Holocaust experience was found to render the elderly more vulnerable rather than less. These findings of greater vulnerability among Holocaust survivors are of particular significance since they stem from a nonclinical group.

Age Factors↗
PubMed1989

Tumor DNA content in resectable, primary colorectal carcinoma.

Tumor DNA content was measured in patients with colorectal carcinoma in order to determine whether tumor ploidy was a prognostic indicator independent of standard clinical and pathologic characteristics. One hundred forty-seven patients were analyzed who had their primary resectable colorectal carcinomas resected with curative intent from 1974 to 1981. Aneuploid colorectal cancers (i.e., tumors with abnormal DNA content) tended to be less well-differentiated, to invade the serosa or extend beyond, and to have lymph node metastases rather than diploid tumors (i.e., tumors with normal DNA content). A significantly increased rate of recurrent disease was demonstrated in patients with aneuploid tumors as opposed to those with diploid tumors (46.7% vs. 4.8%, respectively [p less than 0.001]). In addition, patients with aneuploid tumors exhibited a significantly decreased disease-free and overall survival in comparison with patients with diploid colorectal carcinomas. A Cox regression analysis demonstrated that tumor DNA content was the single most important factor in predicting recurrence or death from colorectal carcinoma.

Aged↗
PubMed1986

Bureaucracy's impact on decision making in long-term care.

Are decisions about the most effective services for a client influenced by factors other than the client's needs, available resources, and the social worker's skill and judgment? This study of social workers in two social welfare agencies in Israel examines how practice settings affect workers' decisions and suggests that environmental variables have a pervasive impact.

Aged↗
PubMed1984

The continent colostomy.

A two-part silicone device for stoma control is presented. Methods for implantation and use are described. Initially used in five patients, it has proven safe and effective.

Colostomy↗
PubMed1984

The aortic valve. Colonic axis.

In the past few years, a correlation has been recognized between calcific aortic stenosis and lower gastrointestinal bleeding in elderly patients. It has been suggested by several authors that mucosal arteriovenous malformations, usually in the right colon, are the cause of bleeding in those patients. Although attention is usually focused on doing a partial colectomy (usually right hemicolectomy) for treating colonic arteriovenous malformation bleeding, several patients with calcific aortic stenosis and gastrointestinal bleeding have been reported in whom bleeding stopped after aortic valve replacement alone. The purpose of this paper is to review the possible mechanisms of lower intestinal bleeding in patients with calcific aortic stenosis, delineate the methods of diagnosis, and finally, to outline the appropriate surgical management.

Aged↗