Biomedical subjects

Z Zakay-Rones

Publications and source records attributed to Z Zakay-Rones.

At least 37 records · Page 2Linked to original sources

PubMed1997

Interleukin-7-enhanced cytotoxic T lymphocyte activity after viral infection in marrow transplanted mice.

Lethally irradiated BALB/c mice were reconstituted by syngeneic bone marrow transplantation (BMT), and injected with recombinant interleukin 7 (rIL-7), recombinant interleukin 2 (rIL-2), or saline 10 days post-transplantation. Intranasal infection with A/PR8/34 influenza virus 2 weeks after BMT was associated with the highest survival rate in the rIL-7 treated group. The protective mechanism elicited by rIL-7, as manifested by very low virus titers in the lung, involves T and B cell functions. High hemagglutinin inhibition antibody levels were observed on days 7 and 12 post-challenge in the rIL-7 mice. Moreover, the anti-influenza cytotoxic T lymphocyte activity was induced primarily by rIL-7, leaving the effect of rIL-2 on the same level as that of the control. Thus, rIL-7 promotes both T cell-mediated function and B cell production during the immunodeficient state after BMT. This cytokine may prove a potential immunotherapeutic modality in BMT recipients.

Animals↗

PubMed1997

Dehydroepiandrosterone treatment is not beneficial to the immune response to influenza in elderly subjects.

BACKGROUND: Dehydroepiandrosterone (DHEA) is a native steroid with an immunomodulating activity that was suggested to counter-regulate some phenomena of immunosenescence. Recently, it was shown to reverse the age-associated decline of immune response against influenza vaccine in aged mice. The present study was designed to evaluate the effect of DHEA on the immunization of elderly volunteers against influenza. METHODS: Seventy-one elderly volunteers age 61-89 yr were enrolled in a prospective randomized, double-blind study to receive either DHEA (50 mg qd p.o. for four consecutive days starting two days before immunization) or placebo. Antibody response to the vaccine was measured before and 28 days after vaccination. RESULTS: DHEA treatment significantly increased serum DHEA-sulfate (DHEA-S). No enhancement in established immunity was observed. A significant decrease in attainment of protective antibody titer (1:40 or higher) against the A/Texas strain in subjects with nonprotective baseline antibody titer was recorded following DHEA treatment compared with placebo (52% vs. 84%, P < 0.05). Baseline DHEA-S serum levels were inversely related to attainment of immunization in DHEA-treated subjects. Influenza-like morbidity during the winter was low in the study group with no difference between the DHEA and placebo groups. CONCLUSIONS: Although highly effective in aged rodents, a short course of DHEA treatment did not improve the age-related declined response to immunization against influenza in human subjects. Higher baseline DHEA-S levels are not predictive of better immunization against influenza in the elderly.

Aged↗

PubMed1996

Solubilization in Colloidal Immunoclusters

Micelle-like clusters of antibody molecules were prepared by covalent attachment of various hydrophobic groups to the protein molecules. These colloidal clusters were capable of solubilizing two hydrophobic probes, while the solubilizate:solubilizer molar ratio was dependent on the chain length of the hydrophobic groups, the degree of modification, and hence, on the size of the colloidal clusters. By using a fluorescent solubilizate, it was demonstrated that the immunoclusters may have a specific recognition ability.

Journal Article↗

PubMed1996

Preferential cytotoxic effect of Newcastle disease virus on lymphoma cells.

Susceptibility of lymphoma cells (Daudi, HD-Mar) to Newcastle disease virus toxicity was found to be higher than that of lymphoblastoid cells (Milstein) and of resting peripheral blood lymphocyte (PBL). Phytohemagglutinin- and/or pokeweed-mitogen-activated PBL however, exhibited, elevated sensitivity, similar to that of lymphoma cells. The level of cytotoxicity was monitored by cell viability, inhibition of DNA synthesis and release of 51Cr. When Daudi cells were mixed with PBL they were significantly more sensitive to the killing effect of the virus (70% mortality compared to 30% 30 h after infection, P < 0.05). The degree of sensitivity to viral cytotoxicity was unrelated to the efficacy of adsorption, which was similar for all cell lines as shown by immunofluorescent staining and flow cytometry. Also an influenza strain A/PR/8/34 (H1N1) adsorbed but did not affect the viability of any of the cells tested. Our results demonstrate that New-castle disease virus caused preferential damage to lymphoma cells as compared to non-cancerous normal cells.

Burkitt Lymphoma↗

PubMed1996

Enhancement of primary and secondary responses to sheep red blood cells and influenza virus in BALB/c mice by recombinant human interleukin-2.

Treatment with recombinant human IL-2 (rIL-2) is being investigated as a new modality for the control of minimal residual disease in conjunction with autologous bone marrow transplantation for a variety of malignant hematological disorders and certain solid tumors. In investigating the functional role of rIL-2 in T cell dependent humoral immune responses, we determined the level of IgG, IgM, and total antibodies activity in BALB/c mice, with or without rIL-2 administration, before primary or secondary immunization with sheep red blood cells (SRBC) or influenza virus A/PR8/34 (H1N1). Our results show the beneficial effect of pretreatment with rIL-2 in enhancing primary and secondary humoral immune responses to SRBC (p < 0.05) and possibly to influenza virus. Administration of well tolerated doses of rIL-2 before inoculation of antigen or infectious agent is not likely to be harmful and may even enhance protective immunological responses.

Animals↗

PubMed1995

Dehydroepiandrosterone enhances influenza immunization in aged mice.

The effect of DHEA administration on the age-associated decline in immunity against influenza vaccine was studied. Increased humoral response was observed in 16- and 24-month-old mice immunized by live A/PR/8/34 (H1N1) influenza virus following DHEA treatment (a single injection adjacent to immunization). Furthermore, DHEA-treated mice demonstrated increased resistance to postvaccination intranasal challenge with live influenza virus. Thus, DHEA treatment overcomes the age-related defect in the immunity of old mice against influenza.

Aging↗

PubMed1995

The effect of a mesogenic and a lentogenic Newcastle disease virus strain on Burkitt lymphoma Daudi cells.

The destructive effect of Newcastle disease virus (NDV) strains on Burkitt lymphoma Daudi cells was investigated. Interaction of an active and UV-inactivated mesogenic strain (Roakin), as well as an active attenuated lentogenic strain (B1), grown in the allantoic sac of embryonated eggs, at high multiplicity, caused inhibition in cellular DNA synthesis and arrest in cell multiplication, eventually killing of the cells. The lentogenic strain cultivated in chicken fibroblasts exhibited only a moderate activity. The mechanism of the cytolytic effect is presumably linked to the increase in cell membrane permeability indicated by the elevation in 51Cr release. Thus it appears that the massive adsorption and/or penetration of viral particles, active or UV-inactivated (or possibly a toxic component that resides in the virion), damages the plasma membrane and may be responsible for the killing of the cells.

Adsorption↗

PubMed1995

Dehydroepiandrosterone (DHEA) treatment reverses the impaired immune response of old mice to influenza vaccination and protects from influenza infection.

Dehydroepiandrosterone (DHEA) is a native steroid with an immunomodulating activity. Recently it was suggested that its age-associated decline is related with immunosenescence. To examine whether DHEA administration could effectively reverse the age-associated decline of immunity against influenza vaccine, aged mice were simultaneously vaccinated and treated with DHEA. Reversal of the age-associated decline and a significant constant increase of humoral response was observed in treated mice. Increased resistance to post-vaccination intranasal challenge with live influenza virus was observed in DHEA-treated aged mice. Thus, DHEA treatment overcame the age-related defect in the immunity of old mice against influenza.

Adjuvants, Immunologic↗

PubMed1995

Inhibition of several strains of influenza virus in vitro and reduction of symptoms by an elderberry extract (Sambucus nigra L.) during an outbreak of influenza B Panama.

A standardized elderberry extract, Sambucol (SAM), reduced hemagglutination and inhibited replication of human influenza viruses type A/Shangdong 9/93 (H3N2), A/Beijing 32/92 (H3N2), A/Texas 36/91 (H1N1), A/Singapore 6/86 (H1N1), type B/Panama 45/90, B/Yamagata 16/88, B/Ann Arbor 1/86, and of animal strains from Northern European swine and turkeys, A/Sw/Ger 2/81, A/Tur/Ger 3/91, and A/Sw/Ger 8533/91 in Madin-Darby canine kidney cells. A placebo-controlled, double blind study was carried out on a group of individuals living in an agricultural community (kibbutz) during an outbreak of influenza B/Panama in 1993. Fever, feeling of improvement, and complete cure were recorded during 6 days. Sera obtained in the acute and convalescent phases were tested for the presence of antibodies to influenza A, B, respiratory syncytial, and adenoviruses. Convalescent phase serologies showed higher mean and mean geometric hemagglutination inhibition (HI) titers to influenza B in the group treated with SAM than in the control group. A significant improvement of the symptoms, including fever, was seen in 93.3% of the cases in the SAM-treated group within 2 days, whereas in the control group 91.7% of the patients showed an improvement within 6 days (p < 0.001). A complete cure was achieved within 2 to 3 days in nearly 90% of the SAM-treated group and within at least 6 days in the placebo group (p < 0.001). No satisfactory medication to cure influenza type A and B is available. Considering the efficacy of the extract in vitro on all strains of influenza virus tested, the clinical results, its low cost, and absence of side-effects, this preparation could offer a possibility for safe treatment for influenza A and B.

Adolescent↗

PubMed1995

Enteric viral infections in Gaza children--incidence and associated factors and phenomena.

Regular administration of live attenuated polio vaccine (TOPV) to babies in Gaza failed to give adequate protection against infection and disease with wild polio viruses. The possible interference of the "take" of the vaccine was investigated by obtaining demographic, socioeconomic and virological data. More than 100 babies during their first year of life, and their families, were followed. Enteroviruses were isolated in 25.3% and 7.9% of stool samples obtained from healthy babies and babies with diarrhea, respectively. In the same cases, rotaviruses were detected in only 1.9% and 1.4% respectively. It appears that the most common candidates for viral interference in this population are enteroviruses and not rotaviruses, either in healthy babies or in babies suffering from diarrhea.

Adult↗

PubMed1994

Prevalence of viral antibodies in gingival crevicular fluid.

The prevalence of antibodies to CMV, Mumps and Coxsackie virus strains 1, 3 and 4 was studied in 39 samples of gingival crevicular fluids (GCF) obtained from clinical healthy patients and compared to the corresponding antibodies present in the serum of each individual. In spite of the high prevalence of humoral antibodies to CMV (75%), only 24% of the gingival crevicular fluid samples exhibited IgG or IgA antibodies to this virus. The differences in the prevalence of antibodies against Mumps virus in the sera and GCF were even greater: whereas 87% of the patients exhibited serum antibodies, not even a single gingival fluid sample was found to be positive. Antibodies to Coxsackie B strains 1, 3 and 4 were found in 72%, 63% and 52% of the sera and in 25%, 19% and 33% of the gingival fluid samples (IgG only). The presence of the antibodies and their profile in GCF and serum is different. The mechanism of possible permeation is not clear but it seems that viral antibodies in this milieu are not derived from the serum solely by passive transudation, and that the antibodies are produced locally at least in some of the GCF specimens.

Adolescent↗

PubMed1992

Detection of herpes simplex virus in gingival tissue.

The presence of herpes simplex virus (HSV) antigens was shown by immunofluorescence staining in 26 of 66 (39.3%) specimens of clinically healthy gingiva, but only one sample contained infectious virus. HSV DNA sequences were clearly identified in intact gingival cells by dot blot hybridization in one specimen, and a weak pattern in a second one. Both specimens harbored viral antigens. These findings of viral genome and protein expression suggest that the virus is present in the latent form in the gingiva.

Adult↗

PubMed1992

Cytokine-induced resistance to microbial infections in normal, immunosuppressed and bone marrow transplanted mice.

We studied the efficacy of in vivo and in vitro treatments with IL-1, IL-2, IL-3, and GM-CSF in the protection against bacterial (Salmonella typhimurium), fungal (Candida albicans) and viral (influenza virus A/PR8) infections, of normal, sublethally irradiated and lethally irradiated, bone marrow (BM) reconstituted mice. In parallel, the cytokines were tested for their ability to potentiate hematopoietic activity in vitro and in vivo. We demonstrate that, under the experimental conditions employed, IL-1 had the best protective activity against the three micro-organisms in both normal and immunocompromised mice when administered in vivo. Administration of IL-2 led to increased resistance in normal but not in immunodeficient mice, whereas GM-CSF had no beneficial effects. In contrast, preincubation of BM cells in these cytokines, singly or combined, prior to transplantation to lethally irradiated mice, did not confer protection against subsequent infection, although it increased the number of BM derived CFU-GM in culture (except in the case of IL-2). Administration of IL-1 or GM-CSF to BM transplanted mice facilitated WBC recovery, whereas IL-2 delayed it. Collectively, the data suggest that IL-1, alone or combined with other cytokines, may be beneficial in the prevention or treatment of microbial infections in immunocompromised and BM transplanted patients. It can also be concluded that enhanced hematopoietic recovery may not always coincide with the development of resistance to micro-organisms.

Animals↗

PubMed1991

Killing of Burkitt-lymphoma-derived Daudi cells by ultraviolet-inactivated vaccinia virus.

Interaction of active and UV-inactivated vaccinia virus at high multiplicity caused cytological changes and inhibition in cellular protein and DNA synthesis, thus arresting the multiplication of Burkitt-lymphoma-derived Daudi cells and eventually killing the cells. Adsorption to the cells but the lack of penetration was evident by immunofluorescence, electron microscopy and [3H]thymidine-labeled virus incorporation. Viral DNA synthesis or virus replication was not demonstrated. Thus, it appears that the massive adsorption of viral particles, active or UV-inactivated, or possibly a "toxic" component that resides in the virion, damages the plasma membrane and may be responsible for killing the cells by a mechanism of lysis from without.

Animals↗

PubMed1991

The effect of total or partial T lymphocyte depletion on susceptibility to influenza virus infection and development of antiviral immunity in lethally irradiated mice reconstituted with immune syngeneic bone marrow grafts.

In a previous study, we showed that lethally irradiated mice reconstituted with bone marrow (BM) enriched with spleen cells obtained from A/PR8/34 influenza virus-immune donors had an improved survival rate compared to the survival seen in recipients of naive BM, immune BM or T cell-depleted BM obtained from immune mice. Our purpose was to determine which cell population was responsible for this effect. We therefore compared the resistance to influenza virus of lethally irradiated BALB/c mice reconstituted with BM from immune donors enriched with 20% spleen cells following either incubation with anti-Thy-1, anti-Lyt-2 or anti-L3T4 monoclonal antibodies prior to transplantation, thereby leading to in vivo depletion of antibody-treated lymphocyte subsets. Mice were infected with influenza virus 1 day after BM transplantation. Equal survival rates were observed in recipients of unmanipulated BM and spleen cells obtained from immune donors and recipients of similar inocula treated with monoclonal anti-helper (L3T4) or anti-cytotoxic/suppressor (Lyt-2) antibodies prior to inoculation. The survival rate of all these groups was increased in comparison with mice receiving anti-Thy-1 treated BM and spleen cells, suggesting that both L3T4 and Lyt-2 T cell subsets play a role in protection against virus infections.

Animals↗

PubMed1991

Increase in concanavalin A cap formation on lymphoma cells following interaction with inactive influenza viruses.

Binding of the lectin Con A to its ligand on the cell surface of normal circulating lymphocytes induces capping in 28-32% of these cells. This Con A cap formation is markedly decreased in malignant cells from the human hematopoietic system. Among others, the human lymphoma Daudi cell line exhibit a cap formation with Con A in only 5-10% of the cells. In this study, we found that inactivated influenza viruses induced changes in the cell surface membrane of Daudi cells resulting in an increased percentage of Con A cap forming cells (30-40%). This phenomenon occurred independently of viral replication and was initiated by adsorption of inactivated viral particles or isolated hemagglutinin and neuraminidase viral glycoproteins. This phenomenon may be due to the binding of Con A molecules to viral receptors and to cell receptors leading to crosslinking of Con A receptors that will induce their mobility and the formation of a cap. Alternatively, experiments performed with cytochalasin B and colchicine suggest that the viral interaction with the cell membrane may have induced changes in the cytoskeleton at the level of microtubules. These changes induced increased lateral movement of the Con A receptors resulting into formation of a cap.

Adsorption↗

PubMed1990

Augmentation of tumor cell immunogenicity by viruses--an approach to specific immunotherapy of cancer.

Several viruses have been evaluated as potential agents for cancer treatment using either their oncolytic properties, in order to lyse cancer cells, or their potential augmenting effects on the immune response to tumors. However, the direct oncolytic effect was found to be limited in time, in scope and in specificity, whereas the use of viral oncolysates to augment antitumor immunity was shown to be better than tumor cell homogenates or extracts but inferior to noninfected intact tumor cells, attesting for the importance of membrane architecture in preserving immunogenicity of tumor specific surface antigens. In order to get the maximum benefit from this approach we selected a nonlytic virus-tumor cell combination, using Newcastle disease virus as a nonpathogenic virus, to treat the experimental tumor model, Lewis lung carcinoma (3LL) in mice. The virus effectively infected 3LL cells without any cytopathic effect. The infected cells induced strong antitumor immunity, as judged by the appearance of immune cells in the spleen (Winn test and lymphocytotoxicity) and by the resistance to challenge with the 3LL cells after immunization. The antitumor immunity was superior to that obtained with intact noninfected tumor cells. We also designed a treatment protocol using the same virus-tumor cell preparation to treat mice after tumor inoculation. This treatment resulted in cure of 40% of the animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗

PubMed1989

Prevalence of antibody to current influenza virus strains in adolescents.

During the Spring of 1986, 118 pupils aged 15-18 years were surveyed for the presence of humoral antibodies to five influenza strains. Prevalence of humoral immunity (HI) antibodies and immunity was found to be related to the year of the strain's emergence and to length of circulation time in the community. A high percentage of the adolescents were not immune to one or more of the tested strains. More than 40% of the studied group were not immune to the old A strains A/Philipines 2/82 (H3N2) and A/Chile 1/83 (H1N1), nearly 70% were not immune to the two B strains (B/USSR 100/83 and B/Ann Arbor 1/86), and almost the entire group (96%) was unprotected against the recent strain A/Singapore 6/86. Only one pupil was immune to all five strains; 35.6%, 22.2%, 17.8%, and 9.2% were immune to one, two, three, or four of the strains, respectively; and 14.4% were not immune to even one strain.

Adolescent↗