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Biomedical subjects

Arie Ben-Yehuda

Publications and source records attributed to Arie Ben-Yehuda.

11 recordsLinked to original sources
PubMed2006

Interleukin 2 regulation following semi-allogeneic bone marrow transplantation in mice.

Success of allogeneic and autologous bone marrow transplantation (BMT) is hampered by susceptibility to infection during the first two post-treatment years. Further, in treating malignant diseases, impaired anti-host reactivity for donor cells may contribute to a high rate of relapse. Both complications are a consequence of immune deficiency involving B and T lymphocytes. The present study evaluates several key parameters of the immunologic reconstitution mechanism in mice subjected to myeloablative total body irradiation following semi-allogeneic (parental) BMT. This resulted in a gradual reduction of splenic CD3, CD4 and CD8 cells until day 45 post-BMT. Concomitantly, there was an increase in monocytes and CD4+/CD8+ (double positive) cells, accompanied by a persistent elevation in the percentage of B lymphocytes. The total thymic and splenic T cell populations were reduced until day +30. The cellular reduction correlated with the poor proliferative response of the thymic and splenic cells. A decrease occurred in IL-2 mRNA expression in thymic cells during days 15-20 post-transplant, corresponding with the low level of IL-2 secretion in the spleen and thymus of the transplanted mice. In conclusion, following semi-allogeneic BMT, there was an overall immune down-regulation in the cells, gene and protein levels. Reduced immunological responsiveness following BMT reinforces the need for improving the immune dysfunction by immunotherapy post-BMT.

Animals↗
PubMed2004

An association study of a polymorphism in the heparan sulfate proteoglycan gene (perlecan, HSPG2) and Alzheimer's disease.

Accumulating evidence indicates that the heparan-sulfate-proteoglycan (perlecan, HSPG2), as well as other specific proteoglycans, are involved in amyloidogenesis and tau aggregation in Alzheimer's disease (AD). Moreover, the HSPG2 is located on chromosome 1p36, a region of linkage to late-onset AD (LOAD). These two criteria, pathological and positional, make the HSPG2 an interesting candidate for an association with AD. We performed a case-control association study between the common intron 6 BamHI polymorphism at a region of putative heparan-sulfate (HS) attachment sites in the HSPG2 gene and sporadic AD in Jews. No association was detected with AD, neither as a risk factor nor as a modifier gene affecting the age at disease onset and disease progression. In addition, no interactive effect was found with the known risk factor for AD, the apolipoprotein E (APOE) epsilon4. These findings show no evidence for association between HSPG2 intron 6 BamHI polymorphism and AD in our population.

Age of Onset↗
PubMed2004

The Fas promoter polymorphism at position -670 is not associated with late-onset sporadic Alzheimer's disease.

The Fas antigen is a cell surface receptor-mediating cell apoptosis. Recent studies have demonstrated that Fas-associated apoptosis is involved in the pathogenesis of Alzheimer's disease (AD). Moreover, the Fas gene is located on chromosome 10q24.1, a region of linkage to late-onset AD (LOAD). These two criteria, pathobiological and positional, make the Fas antigen an interesting candidate for an association with AD. We performed a case-control association study between the common A/G polymorphism at position -670 in the Fas gene (TNFSRF6) promoter and sporadic AD in Jews, investigating whether this locus acts as a risk factor or whether it has a modifying effect. An association has recently been detected by Feuk et al. in the Scottish population between this locus and the risk of early-onset AD (EOAD), but not of LOAD. In agreement with Feuk et al., we found no association between this locus and the risk of LOAD (n = 86). However, in our small sample of patients with EOAD (n = 19), no association was found either. No interactive effect was found between the Fas promoter polymorphism at position -670 and the known risk factor of LOAD, apolipoprotein E epsilon4, and no association was detected with disease progression. These findings show no evidence for an association between the Fas promoter polymorphism at position -670 and AD in our population.

Aged↗
PubMed2004

Engineering anticancer T cells for extended functional longevity.

Like other somatic cells, human T lymphocytes have a finite replicative capacity in vitro, and, by implication and consistent with the limited data available, in vivo as well. An accumulation of dysfunctional T cells may be detrimental under conditions of chronic antigenic stress (chronic infection, cancer, autoimmunity). Using T cells from young donors to model the process of T cell clonal expansion in vitro under these conditions reveals age-associated increasing levels of oxidative DNA damage and microsatellite instability (MSI), coupled with decreasing DNA repair capacity, telomerase induction and telomere length, decreased levels of expression of the T cell costimulator CD28 and consequently reduced secretion of the T cell growth factor interleukin-2 (IL-2). However, data from similar experiments using T cell clones (TCCs) derived from extremely healthy very elderly donors ("successfully aged") indicate that DNA repair is better maintained, MSI less prevalent, and (already short) telomere lengths are maintained. Nonetheless, oxidative DNA damage is seen to the same extent, and clonal longevity is also similar in these clones. DNA damage levels are reduced by culture in 5% oxygen, but longevity is not improved. This may be because of the requirement for intermittent reactivation via receptor pathways dependent on free radical production in T cells. These recent findings from our international immunosenescence research consortium suggest that strategies other than telomere maintenance, better protection against free radicals, or improved DNA repair will be required for functional longevity extension of human TCCs. To obtain sufficient cells for adoptive immunotherapy of cancer, alternative avenues need exploration; currently, these include enforced expression of certain heat shock proteins and proteasome components, and interference with the expression of negative regulatory receptors expressed by T cells.

Antigens↗
PubMed2003

Immunogenicity and safety of a novel IL-2-supplemented liposomal influenza vaccine (INFLUSOME-VAC) in nursing-home residents.

Influenza and its complications account for substantial morbidity and mortality, especially among the elderly. In young adults, immunization provides 70-90% protection, while among the elderly the vaccine may be only </=50% effective; hence, the need for new, more immunogenic vaccines. We compared the safety and immunogenicity of a novel, interleukin-2 (IL-2) -supplemented trivalent liposomal influenza vaccine (designated INFLUSOME-VAC) with that of a commercial trivalent split virion vaccine in community-residing elderly volunteers (mean age 81 years) in winter of 2000/2001. Eighty-one individuals were randomly assigned to be vaccinated intramuscularly, either with the standard vaccine (n=33) or with INFLUSOME-VAC (n=48) prepared from the former. The two vaccines contained equal amounts of hemagglutinin (HA) ( approximately 15 microgram of each viral strain); INFLUSOME-VAC consisted of liposomal antigens admixed with liposomal human IL-2 (Lip IL-2) (33 microgram = 6x10(5) IU/dose). At 1 month post-vaccination, seroconversion rates (tested by hemagglutination inhibition) for the A/New Caledonia (H1N1) and A/Moscow (H3N2) strains were significantly higher (P=0.04) in the INFLUSOME-VAC group (65 versus 45%, 44 versus 24%, respectively). Moreover, INFLUSOME-VAC induced a greater anti-neuraminidase (NA-N2) response (P<0.05). Anti-IL-2 antibodies were undetected, and no increase in anti-phospholipid IgG antibodies was found in the INFLUSOME-VAC group. Adverse reactions were similar in both groups. Thus, INFLUSOME-VAC appears to be both safe and more immunogenic than the currently used vaccine in the elderly.

Adjuvants, Immunologic↗
PubMed2003

An association study of the codon 72 polymorphism in the pro-apoptotic gene p53 and Alzheimer's disease.

Recent studies have demonstrated that p53-associated apoptosis is involved in the pathogenesis of Alzheimer's disease (AD). We performed a case-control association study between sporadic AD and the common proline/arginine polymorphism at codon 72 in the pro-apoptotic gene p53, in 109 sporadic AD patients and in 111 controls. This polymorphism has been intensively investigated for association with cancer, but so far not with AD and neurodegeneration. We found no association between this locus and the risk for AD. No association was detected also for the age at disease onset and for disease progression, and no interactive effect was found with apolipoprotein E e4. These findings show no evidence for an association between p53 codon 72 polymorphism and AD in our population.

Aged↗
PubMed2003

Local and systemic immune response in nursing-home elderly following intranasal or intramuscular immunization with inactivated influenza vaccine.

Intramuscular (IM) influenza vaccines are only 30-40% effective in preventing clinical illness among the elderly, and their effectiveness in eliciting mucosal response may be even lower. The aim of the present study was to evaluate the immunological effect of a novel inactivated intranasal (IN) trivalent whole influenza virus vaccine among nursing-home elderly. Twenty-one institutionalized elderly subjects were vaccinated IN with an inactivated novel vaccine, twice, 21 days apart, and with no adverse effects. Twenty-two subjects were vaccinated once with a commercial IM vaccine. Viral strains used in the 1998/9 vaccine (20 microg of each per dose) were A/Beijing/262/95, A/Sydney/5/97 and B/Harbin/7/94. Serum antibodies (IgG and IgM) and nasal IgA were determined by the hemagglutination inhibition (HI) test and enzyme-linked immunosorbent assay (ELISA), respectively. Mucosal antibody response to the three vaccine strains was detected in 47.6-71.4% and 18.1-31.8% of IN and IM immunized subjects, respectively. Serum antibody response to the three antigens tested was detected in 20.0-61.9% and 18.2-72.7% of IN and IM immunized subjects, respectively. Seroconversion was not significantly different after IN or IM vaccination for both A/Sydney and B/Harbin, but higher for A/Beijing following IM vaccination. On study completion, 57.1, 65.0 and 50.0% of IN vaccinees were seroprotected to A/Beijing, A/Sydney and B/Harbin, respectively. Similarly, 68.1, 77.2 and 54.5% were immune after IM vaccination. The IN vaccine tested was significantly more effective than the IM vaccine in inducing mucosal IgA response. This may prevent influenza at its early stages and thus contribute to the reduction of morbidity and complications in nursing-home elderly.

Administration, Intranasal↗
PubMed2003

A polymorphism in the complement component C1r is not associated with sporadic Alzheimer's disease.

A growing body of evidence suggests that Alzheimer's disease (AD) is associated with local inflammation processes. Complement activation is one of the cardinal pathological features of the inflammation. Intensive AD association studies investigating polymorphisms in inflammatory-related genes have been recently performed, mainly in cytokines, but much less has been focused on AD association with polymorphisms in complement components. We performed a case-control association study between the codon 135 polymorphism in the complement component C1r gene and sporadic AD. No association was detected with AD: neither as a risk factor, and nor as a modifier gene affecting the age at disease onset and disease progression. No interactive effect was found with apolipoprotein E e4. These findings show no evidence for association between C1r codon 135 polymorphism and AD in our population.

Aged↗
PubMed2003

Immunogenicity and safety of a novel liposomal influenza subunit vaccine (INFLUSOME-VAC) in young adults.

Influenza and its complications account for substantial morbidity and mortality among young adults and especially among the elderly. In young adults, immunization provides 70-90% protection, while among the elderly the vaccine may be only 30-40% effective; hence the need for new, more immunogenic vaccines. We compared the safety and immunogenicity of a novel IL-2-supplemented liposomal influenza vaccine (designated INFLUSOME-VAC) with that of a commercial subunit vaccine and a commercial split virion vaccine in young adults (mean age 28 years) in the winter of 1999-2000. Seventy-three healthy young adults were randomly assigned to be vaccinated intramuscularly with the following: a commercial subunit vaccine (n = 17, group A), INFLUSOME-VAC (n = 36, group B), and a commercial split virion vaccine (n = 20, group C). The three vaccines contained equal amounts of hemagglutinin (approximately 15 microg each) from the strains A/Sydney (H3N2), A/Beijing (H1N1), and B/Yamanashi. INFLUSOME-VAC induced higher geometric mean HI titers and higher-fold increases in HI titers against all three strains, compared with the two commercial vaccines. In addition, seroconversion rates for the A/Sydney and B/Yamanashi strains were significantly higher (P < 0.05) compared with the split virion vaccine, and significantly higher for the three strains compared with the subunit vaccine (69-97% vs 35-65%, P < or = 0.02). Moreover, the anti-neuraminidase response was significantly greater (P = 0.05) in group B vs group A. INFLUSOME-VAC caused mild local pain at the injection site in a significantly higher proportion of the vaccinees (83%). Thus, INFLUSOME-VAC is an immunogenic and safe vaccine in young adults.

Adolescent↗
PubMed2003

Response to influenza vaccination in community and in nursing home residing elderly: relation to clinical factors.

Intramuscular (IM) influenza vaccines are about 50% effective in preventing respiratory illness among the elderly. The aim of this study was to identify factors associated with immune response to influenza vaccination among nursing home and community-residing elderly. 114 nursing home (NHE) and 62 community residing elderly (CE) were vaccinated with a commercial IM vaccine. Serum antibodies were evaluated by HIA, and the impact of subjects' clinical characteristics on seroconversion was determined. Factors that were associated with low seroconversion among NHE, included: type II diabetes [for B/Harbin: p=0.044, OR 0.12, (CI: 0.015-0.94)], and antibody titer prior to vaccination A/(H1N1): p=0.03, OR 2.38, (CI: 1.09-5.22); A/(H3N2): p=0.015, OR 2.68 (CI: 1.22-5.92), B/Harbin: p=0.057, OR 4.46 (CI: 0.96-20.85)]. Factors that were associated with lower seroconversion CE elderly, included older age [A/(H1N1): p=0.008, OR 0.846, (CI 0.75-0.96), B/Harbin: p=0.016, OR 0.812, (CI:0.69-0.96)], and antibody titer prior to vaccination A/(H1N1): p=0.029, OR 4.08, (CI: 1.16-14.37); A/(H3N2): p<0.0001, OR 11.495 (CI: 3.18-41.55)]. There was no significant difference in seroconversion between nursing home residing elderly and community elderly. We conclude that Type-II diabetes and antibody titer>1:40 prior to vaccination are associated with reduced response to the influenza vaccination in nursing home elderly.

Aged↗