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Biomedical subjects

E Yefenof

Publications and source records attributed to E Yefenof.

At least 19 recordsLinked to original sources
PubMed2006

The outcome of a preventive dental care programme on the prevalence of localized aggressive periodontitis in Down's syndrome individuals.

BACKGROUND: Periodontal disease in Down's syndrome (DS) individuals develops earlier and is more rapid and extensive than in age-matched normal individuals. The present study evaluated a group of DS patients, who had been participating in a 10-year preventive dental programme, for the impact of the programme on their periodontal status. METHODS: Thirty DS patients (mean age 23.3 +/- 4 years) were compared with 28 age-matched healthy controls (mean age 22.8 +/- 5 years). The hygiene level, gingival condition and periodontal status (periodontal probing depth, clinical attachment level and radiographic alveolar bone loss) were determined. RESULTS: In spite of similar oral hygiene and gingival measures, DS patients, as opposed to the control ones, had a severe periodontal disease. The prevalence, extent and severity of periodontitis in the DS group were significantly greater than in the control group. The teeth most commonly and severely affected were the lower central incisors and the upper first molars. DS patients lost significantly more teeth due to periodontitis. CONCLUSIONS: The clinical and radiographic picture found in the present DS group is characteristic of localized aggressive periodontitis. Within the limitations of this study, it seems that the preventive dental programme had no effect on periodontal destruction progression of localized aggressive periodontitis in DS individuals and that impaired oral hygiene plays a relatively minor role in the pathogenesis of this disease. Future controlled studies are needed to assess the effectiveness of different preventive dental programmes in preventing the progression of periodontitis in DS patients.

Adolescent↗
PubMed2006

Salivary LL-37 secretion in individuals with Down syndrome is normal.

Antimicrobial peptides play an important role in the innate immune response. Deficiency in salivary LL-37 antimicrobial peptide has been implicated in periodontitis in patients with morbus Kostman syndrome. Down syndrome is associated with periodontitis, diminished salivary flow, and salivary immunoglobulin deficiency. In the present study, levels of LL-37 and its hCAP18 precursor were measured in saliva samples from young individuals with Down syndrome and compared with levels in those from age-matched healthy controls. LL-37 and human cathelicidin antimicrobial protein (hCAP18) were detected in whole but not in parotid saliva. hCAP18 was more abundant than LL-37. The concentrations of salivary hCAP18 and LL-37 were found to be higher in individuals with Down syndrome than in healthy controls, but their secretion rates were similar. We concluded that, while the adaptive immunity of individuals with Down syndrome is impaired at the oral mucosa, the secretion rate of the LL-37 component of the innate immune system is normal.

Adult↗
PubMed2002

A link between parotid salivary Ig level and recurrent respiratory infections in young Down's syndrome patients.

The purpose of the present investigation was to assess the correlation between recurrent respiratory infections and the levels of salivary Ig in a group of young Down's syndrome (DS) individuals. Twenty-three DS and 10 age- and sex-matched healthy individuals were included. DS individuals who had experienced three or more upper respiratory tract infections (n = 10) in the previous 12 months were compared to DS individuals who had not experienced recurrent respiratory infections (n = 13) and to healthy controls (n = 10). A statistically significant reduction in the Ig salivary secretion rate was recorded in the subgroup with recurrent respiratory infections. No significant differences were seen between the subgroup without recurrent respiratory infections and controls. It is suggested that the secretory immune system provides local immune protection against pathogens in the respiratory tract. Detection of salivary Ig levels may serve as a predictor of the susceptibility of DS individuals to recurrent respiratory tract infections.

Adolescent↗
PubMed2002

Severe impairment of secretory Ig production in parotid saliva of Down Syndrome individuals.

Infections associated with Down Syndrome (DS) are prevalent in the mucosal-gastrointestinal and respiratory systems, for reasons that are uncertain. The purpose of the present study was to assess the levels of parotid salivary immunoglobulins (Ig) in a group of DS individuals as a possible factor in the susceptibility of mucosal surfaces to infections. Twenty-nine DS and 10 age- and sex-matched healthy individuals were included. Salivary flow rate and IgA, IgG, and IgM concentrations were recorded. The secretion rates of IgA and IgG were diminished by 83% (p < 0.001) and 75% (p = 0.05), respectively, whereas the secretion rate of IgM was not statistically significantly lower. Analysis of the data suggests that DS individuals are immunodeficient in the humoral mucosal immune response. This may explain, in part, the high incidence of recurrent infections in target organs of the secretory immune system in DS subjects.

Adolescent↗
PubMed2000

The growth and metastasis of human, HER-2/neu-overexpressing tumor cell lines in male SCID mice.

HER-2/neu is overexpressed on a variety of human adenocarcinomas and overexpression has been associated with a poor prognosis. For this reason, HER-2 has become an attractive target for immunotherapy. To facilitate testing of anti-HER-2-monoclonal antibodies (MAbs) and immunotoxins (ITs), we have evaluated the in vivo growth and metastatic spread of three HER-2-overexpressing human breast cancer cell lines (BT474, MDA-MB-453 and HCC1954) and one ovarian cancer cell line (SKOV3.ip1) in pre-irradiated male SCID mice using subcutaneous (s.c.), intravenous (i.v.) and intraperitoneal (i.p.) routes of injection. All the cell lines tested grew as s.c. tumors and the growth of BT474 and MDA-MB-453 cells after s.c. injection was improved by co-inoculation with Matrigel. Metastases to the lungs were detectable by PCR or histopathology after s.c. injection of BT474 and to a much lesser extent after s.c. injection of HCC1954, MD-MB-453 and SKOV3.ip1 cells. I.p. injection of HCC1954 and SKOV3.ip1 cells produced fatal ascites while i.v. injection of SKOV3.ip1, but not BT474 or MDA-MB-453 cells, resulted in infiltration of lungs and death within 9-11 weeks.

Animals↗
PubMed2000

p53 and thymic 'death by neglect': thymic epithelial cell-induced apoptosis of CD4+8+ thymocytes is p53-independent.

The involvement of the tumor suppressor protein, p53, in thymic epithelial cell-induced apoptosis of CD4+8+ (double positive) thymocytes, was studied in an in vitro model consisting of a thymic epithelial cell line (TEC) and thymocytes. p53 expression was not augmented in double positive (DP) thymocytes upon co-culturing with TEC, although extensive apoptosis was observed. In the same cells, p53 expression was upregulated in response to low ionizing irradiation, which was accompanied with massive apoptosis. Moreover, TEC induced apoptosis in two DP thymomas, derived from p53(-/-) mice, and in a double positive thymoma clone expressing mutant p53. The extent and kinetics of TEC-induced apoptosis was not affected by the status of p53 in the thymocytes tested. We conclude that thymic epithelial cell-induced apoptosis of immature DP thymocytes is p53-independent and apparently, involves a different apoptotic pathway than that triggered by DNA damage.

Animals↗
PubMed1999

Apoptosis of thymic lymphoma clones by thymic epithelial cells: a putative model for 'death by neglect'.

We have previously described an in vitro system in which thymic epithelial cells induce apoptosis in CD4+ 8+ thymocytes or thymic lymphoma cells, in the absence of an exogenous antigen. A thymic epithelial cell line (TEC) recapitulated the response, by inducing apoptosis in CD4+ 8+ thymocytes of the thymic lymphoma clone, PD1.6. The present study pursues the involvement of the T-cell receptor (TcR) in the response of PD1.6 to TEC. TcR cross-linking did not cause apoptosis of PD1.6, although it induced tyrosine phosphorylation of p95vav. In contrast, TEC did not induce phosphorylation of p95vav but induced apoptosis of PD1.6 cells. These results suggest that TcR-evoked signals are not involved in TEC-induced apoptosis of PD1.6. Intracellular calcium chelation, using BAPTA-loaded PD1.6 cells, diminished TEC-induced apoptosis. Protein kinase C depletion in PD1.6 cells augmented their apoptotic response to TEC. Thus, the response of PD1.6 to TEC is calcium-dependent and inhibited by PKC. Likewise, the apoptotic response of PD1.6 to A23187 was abrogated by PKC activation. PD1.6 cells may represent an immature double positive thymocyte population, which does not undergo negative selection. The interaction of PD1.6 with TEC may thus serve as a model for the TcR-independent 'Death by Neglect', which takes place in the thymus during thymocyte development.

Animals↗
PubMed1998

Complement receptor 3 of macrophages is associated with galectin-1-like protein.

We have previously identified a 16-kDa protein with a pI of 5.1 (P16/5.1) that is associated with macrophage CR3. Microsequencing of P16/5.1 indicated exclusive homology to the beta-galactoside-binding lectin, galectin-1. Abs specific to a galectin-1 unique peptide reacted with P16/5.1. The association of P16/5.1 with CR3 was specifically inhibited by lactose, which binds with high affinity to galectin-1. These data together with similarities in molecular mass and pI suggest that P16/5.1 is galectin-1. Two-color immunofluorescence staining revealed the expression of galectin-1 on the macrophage surface and its colocalization with CR3. However, a surplus of CR3 was free of galectin-1, and some galectin-1 molecules were associated with cell surface receptors other than CR3. Based on these results we propose two models depicting the functional significance of CR3-galectin-1 association: 1) homodimeric galectin-1 possessing a divalent sugar binding site may act as an extracellular adapter molecule that cross-links CR3 with other receptors; and 2) association of galectin-1 with beta-galactosides on the extracellular domain of CR3 may modify the binding affinity of the receptor to its ligand. These possibilities are not mutually exclusive and can clarify the mode by which CR3 transmits signals in macrophages.

Animals↗
PubMed1997

Prophylactic intervention in RadLV-induced lymphomagenesis with an anti-IL-4 monoclonal antibody.

Intrathymic inoculation of the radiation leukemia virus (RadLV) into C57BL/6 mice induces thymic lymphomas after 4-6 months. During premalignant latency, a population of RadLV-infected prelymphoma (PL) cells (whose survival is dependent on autostimulation with IL-4) persists in the thymus. PL cells explanted from RadLV-inoculated mice can be propagated in cultures containing IL-4, and in vitro growth of PL cells is effectively inhibited by anti-IL-4 antibodies. We subjected RadLV-inoculated mice to prophylactic treatment with anti-IL-4 antibodies and a virus-specific immunotoxin (IT). Administration of IT delayed the onset of lymphoma but was not curative. Anti-IL-4 antibodies had a similar effect when administered at low doses. High doses of anti-IL-4, given 3-5 weeks after virus inoculation, provided complete protection against lymphoma. These results demonstrate the effectiveness of prophylactic intervention during premalignancy by using antagonists that restrain the growth of PL cells.

Animals↗
PubMed1996

T cell receptor-independent apoptosis of thymocyte clones induced by a thymic epithelial cell line is mediated by steroids.

We have studied the mechanisms involved in TcR-independent apoptosis of radiation leukemia virus (RadLV)-transformed thymocyte clones induced by a thymic epithelial cell line (TEC). TEC induced apoptosis of an immature CD4+8+3+ (PD1.6) but not of a CD4-8-3- (B10) thymocyte clone. TEC-derived conditioned medium did not mimic the signal induced by TEC in PD1.6 cells. However, the TEC-resistant clone B10 apoptosed in response to TEC, provided that PD1.6 cells were also present in the culture. This effect on bystander cells suggests that a secreted factor was involved. The involvement of glucocorticoid hormones as potential mediators was addressed. PD1.6 cells apoptosed in response to dexamethasone or a cell-permeating analog of cAMP, while BIO cells were relatively resistant to dexamethasone. TcR cross-linking inhibited both TEC- and dexamethasone- but not cAMP-induced apoptosis. Aminoglutethimide and Ru38486 inhibited TEC-induced apoptosis of PD1.6 cells, whereas Ru28318 had a negligible effect. The results suggest that steroid hormones are involved in TcR-independent apoptosis of immature double-positive thymocyte clones induced by TEC.

Aminoglutethimide↗
PubMed1996

MHC non-restricted, CD95-independent apoptosis of immature thymocytes induced by thymic epithelial cells.

The interaction of thymocytes with thymic epithelial cells in the absence of an exogenous antigen was studied in vitro. Thymic, but not splenic epithelial cells induced apoptosis of thymocytes. A thymic epithelial cell line (TEC) induced apoptosis of thymocytes but not of splenic T-cells. The target population for TEC-induced death were immature CD4(+)8(+) (double positive), but not mature single positive thymocytes. TEC also induced DNA fragmentation in day 18 foetal thymocytes, most of which are CD4(+)8(+) cells. Radiation leukemia virus (RadLV)-transformed thymic lymphoma clones expressing various phenotypes reflected this sensitivity, in that a CD4(+)8(+)3(+) clone apoptosed by thymic epithelial cells or TEC. Other, single positive or double negative clones were resistant. Thymocytes from C3H (H-2(k)), C57BL/6 (H-2(b)) and Balb/C (H-2(d)) mice apoptosed equally in response to either C57BL/6 thymic epithelial cells or TEC (H-2(b) x H-2(d)). Likewise, thymocytes from MRLIpr((-/-)) and B6Ipr((-/-)) mice, which do not express CD95 were also apoptosed by TEC.The data suggest that thymic epithelial cells induce MHC non-restricted, Fas-independent apoptosis of immature thymocytes. This response may reflect a mechanism through which thymocytes expressing TcR with no affinity to self MHC/peptide complexes are eliminated.

Journal Article↗
PubMed1996

Salivary immunoglobulins in recipients of bone marrow grafts. III. A longitudinal follow-up of CMV specific antibodies.

Cytomegalovirus (CMV) infection is a major complication of BMT. The oral cavity is a common route for CMV infection, whose protection is provided by salivary anti-CMV antibodies. We developed an ELISA assay for the detection of CMV-specific antibodies in parotid saliva. Saliva of patients receiving BMT from CMV-positive donors was transiently reconstituted with IgG and IgA anti-CMV antibodies shortly after transplantation. The concentration of these antibodies gradually decreased during the 2 months after transplantation and increased again around day 80. A remarkable rise in the salivary concentrations of IgG and IgM anti-CMV was observed shortly after i.v. administration of Sandoglobulin. These results demonstrate, for the first time accurate monitoring of CMV-specific antibodies in saliva using a quantitative ELISA assay. The study suggests that secretion of CMV-specific antibodies in saliva of immunocompromised patients can be reconstituted by donor-derived B and plasma cells transferred with the BM or by i.v. administration of pooled Ig.

Adolescent↗
PubMed1995

Identification and characterization of a novel protein associated with macrophage complement receptor 3.

CR3 is a member of the beta 2 integrin family which functions as a bidirectional signaling receptor. The CR3 is composed of the alpha (CD11b) and beta (CD18) subunits, which contain a short intracytoplasmic domain devoid of catalytic activity. It was therefore postulated that CR3 is associated with intracellular molecules that link it to the cytoplasmic signal transduction apparatus. However, no direct association between such molecules and CR3 have been identified so far. We searched for CR3 co-associated molecules that might regulate the function of this receptor. For this purpose CR3 was immunoprecipitated from radiolabeled bone marrow macrophages using a combination of anti-CD11b and anti-CD18 mAbs. Two-dimensional isoelectric focusing analysis of the immunoprecipitates revealed the two CR3 subunits and an additional 16-kDa protein with an apparent isoelectric point of 5.1. This protein, designated p16/5.1, was intracellular, monomeric, nonglycosylated and noncovalently associated with CR3 but not with CR4. CR3-associated p16/5.1 was also detected in four of six macrophage lines as well as in thymic large macrophages, all of which express cell-surface CR3. We suggest that p16/5.1 may be involved in CR3-mediated function.

Animals↗
PubMed1995

Tumor dormancy and cell signaling. II. Antibody as an agonist in inducing dormancy of a B cell lymphoma in SCID mice.

Tumor dormancy can be induced in a murine B cell lymphoma (BCL1) by immunizing BALB/c mice with the tumor immunoglobulin (Ig) before tumor cell challenge. In this report, we have investigated the immunological and cellular mechanisms underlying the induction of dormancy. BCL1 tumor cells were injected into SCID mice passively immunized with antibody against different epitopes on IgM or IgD with or without idiotype (Id)-immune T lymphocytes. Results indicate that antibody to IgM is sufficient to induce a state of dormancy. Antibodies against other cell surface molecules including IgD and CD44 (Pgp1) had no effect on tumor growth. Id-immune T cells by themselves also had no effect on tumor growth in SCID mice. However, simultaneous transfer of anti-Id and Id-immune T cells enhanced both the induction and duration of the dormant state. In vitro studies indicated that antibody to IgM induced apoptosis within several hours and cell cycle arrest by 24 h. Hyper cross-linking increased apoptosis. The Fc gamma RII receptor played little or no role in the negative signaling. Antibodies that did not negatively signal in vitro did not induce dormancy in vivo. The results suggest that anti-IgM plays a decisive role in inducing tumor dormancy to BCL1 by acting as an agonist of IgM-mediated signal transduction pathways.

Animals↗
PubMed1995

Prophylactic intervention in radiation-leukemia-virus-induced murine lymphoma by the biological response modifier polysaccharide K.

Polysaccharide K (PSK) is a biological response modifier used for adjuvant immunotherapy of malignant diseases. We studied the potential applicability of PSK for preventing tumor progression using an experimental model of murine lymphoma. Mice inoculated with the radiation leukemia virus (RadLV) develop thymic lymphomas after a latency of 3-6 months. However, 2 weeks after virus inoculation, prelymphoma cells can already be detected in the thymus. We found that PSK treatment induced hyperresponsiveness to concanavalin A and heightened production of interleukin-2 (IL-2) and IL-4 in spleen cells of both control and prelymphoma mice. The response was transient and was accompanied with a dominant usage of T cells expressing V beta 8, but other T cell subsets were also stimulated by PSK. T lymphoma cells expressing V beta 8.2 underwent apoptosis when incubated with PSK. Treatment of RadLV-inoculated mice with PSK delayed the onset of overt lymphoma (and mortality) but could not protect the mice from the disease. Combined treatment with PSK and a RadLV-specific immunotoxin prevented synergistically the progression of the prelymphoma cells to frank lymphoma. The results suggest that PSK contains a superantigen-like component that selectively activates V beta 8+ T cells. Its administration prelymphoma mice interfered with the process of lymphoma progression.

Adjuvants, Immunologic↗