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Biomedical subjects

Z Zakay-Rones

Publications and source records attributed to Z Zakay-Rones.

At least 55 records · Page 3Linked to original sources

Failure of influenza vaccination in the aged.

A cohort of 127 nursing home residents aged 60-98 years were vaccinated during the winter of 1985-86 with the A-Chile 1/83 (C), A-Philippines 2/82 (P), and B-USSR (B) commercial influenza vaccines. Before vaccination 40%, 23%, and 69% were susceptible to influenza Ac, Ap, and B, respectively [hemagglutinin inhibition (H.I.) titer less than 1:40]. One month following initial vaccination, 32 patients [25%] remained unprotected against two or all three vaccine strains. These patients were revaccinated with the same influenza vaccine and followed up. At five months 11%, 19%, and 23% of the initial cohort were still unprotected against Ac, Ap, and B strains, respectively. We conclude that two conventional influenza vaccines administered one month apart leave unprotected 30% of healthy elderly people who are initial influenza vaccine failures.

Aged↗

Post-influenzal psychiatric disorder in adolescents.

The association between influenza and psychiatric disorder in adolescents was studied at a time when both were highly prevalent concurrently. First 505 secondary school pupils aged 15-18 completed questionnaires, including a symptom inventory derived from the SCL-90-R. Subsequently, 113 blood samples were examined for influenza antibody titers of five virus strains. Statistical analysis showed that adolescents who had been ill with influenza in the previous six months had significantly more psychiatric disorder than those who had not been ill with influenza in that period.

Adolescent↗

The effect of T lymphocyte depletion on susceptibility to influenza virus infection and development of anti-viral immunity in lethally irradiated mice reconstituted with syngeneic bone marrow grafts.

Lethally irradiated Balb/c mice reconstituted with syngeneic T cell-depleted or syngeneic untreated bone marrow (BM) were able to produce equal levels of hemagglutination inhibition (HI) antibodies at 4 weeks after bone marrow transplantation (BMT) in response to nasal infection with A/PR8 influenza virus given 1 week after BMT. Likewise, no differences in mortality rates could be observed following influenza virus infection 1 day after BMT. Antibody production was detected in 10-20% of BMT recipients. All animals responded to a secondary infection given 2 months later by production of secondary IgG-type HI antibodies. Mice reconstituted with BM enriched with spleen cells obtained from immune donors showed an improved survival rate as compared with recipients of naïve BM, immune BM or T-depleted BM obtained from immune mice. Our results indicate that T cell depletion by itself does not increase susceptibility of syngeneic BMT recipients to virus infection. However, immune spleen cells may play a significant role in conveying protection against influenza virus infections. Although recipients of both immune and naïve intact BM may mount better anti-influenza titers as compared with T-lymphocyte-depleted BMT recipients, it appears that the proportion of immune donor T cells in the marrow inoculum is insufficient for protection against influenza virus infection. Generation of memory cells to influenza viral antigens in the post-BMT period is not impaired in recipients of T-depleted marrow grafts, suggesting that memory cell precursors are unaffected by the T cell depletion procedure, or else that they were regenerated during the immediate post-BMT period from Thy 1.2-negative precursors.

Animals↗

Hypothesis: the gingival tissue as a reservoir for herpes simplex virus.

The reservoir site of Herpes simplex virus (HSV), from the primary infection until reactivation and in between recurrences was found to be in the dorsal roots of the trigeminal ganglion or in the sensory root ganglion. However, the triggering of viral genome in the ganglion does not exclusively explain the recurrences and appearance of skin lesions. Other sites cannot, therefore, be excluded, and virus may well be occult also in extraneural tissues. Herpes virus antigens were found by us in the sulcular epithelium of approximately 60% of patients with clinically healthy gingivae; we therefore hypothesised that the epithelial cells might act as the preferential site for latent HSV. In order to prove this assumption, viral genome should be traced in cells of oral tissues, and efforts should be made to rescue virus.

Antibodies, Viral↗

Local and peripheral cell-mediated immune response to influenza virus in mice.

Presentation of different influenza virus antigens generates different immune responses. Intranasal immunization with either live (VA) or formalin-inactivated (VF) A/PR/8/34 (HON1) influenza virus induced local as well as peripheral cell-mediated immune response (CMI), as evidenced by elevation in 3H-thymidine incorporation. Cell-mediated immune response was detected as soon as 24-48 hr following the application of VA and 4-5 days following VF. Cell-mediated immune response in both instances peaked on the 12th day and disappeared between 16 and 20 days after application. Local CMI response was threefold higher after immunization with VA (SI = 28.6) than with VF (SI = 9.4), while VF induced higher peripheral response (32.0 vs 17.7). The mononuclear cell population in the lungs increased, correlating with a rise in the stimulation index (SI). The percentage of IgA surface-bearing B lymphocytes was significantly higher following IN administration of VA, but not following VF instillation. This corroborated the finding that VF failed to induce local antibody response in the lungs in spite of its capacity to stimulate humoral antibody and CMI responses. Mice immunized intramuscularly with both viral preparations developed a fair humoral antibody response without detectable CMI (peripheral or local).

Administration, Intranasal↗

Arrest of Daudi cell growth by inactive influenza virus in-vitro.

We investigated the destructive capability of three influenza A strains, Victoria, PR8, and their recombinant X47, against the human lymphoma cell line Daudi. Both Victoria and X47 strains share the same envelope glycoproteins (H3N2), while PR8, the second parental strain of X47, differs in its envelope glycoproteins (HON1). The H3N2 strains and particularly the X47 recombinant were cytotoxic to Daudi cells while the HON1 strain was not. To reduce the virulence of the oncolytic viruses, we inactivated them either with heat (56 degrees C/45 min) or with formalin. Both treatments significantly reduced the infectivity of the viruses. The X47 virus treated with formalin retained its hemagglutinin (HA) and neuraminidase (NA) activities but lost its cytotoxic potential. On the other hand, the heat-treated X47 virus retained its HA activity, lost its NA activity, but preserved its cytotoxic potential. Thus, the heat-inactivated X47 virus (X56) was the most effective non-virulent oncolytic agent we tested. The X56 virus arrested Daudi cell multiplication in-vitro by inhibiting cellular DNA synthesis. The mechanism by which X56 inhibited Daudi cell DNA synthesis was not related to interferon induction in Daudi cells, and did not necessarily involve the activation of the Epstein-Barr virus (EBV) genome present in Daudi cells. Although the mechanism remains unclear, the oncolytic potential of the X56 virus on Daudi cells was demonstrated.

Burkitt Lymphoma↗

Visualization of the fate of inactive influenza viruses in Daudi cells by electron microscopy.

The replication of active and inactivated influenza viruses in Daudi lymphoma cells was studied by immunofluorescence and electron microscopy. In a previous study, we demonstrated that active and heat-inactivated X47 (H3N2) virus arrested Daudi cell growth by inhibiting cellular DNA synthesis while formalin-treated X47 virus did not. Transmission electron microscopic studies revealed that both the active and the heat-inactivated X47 virus penetrated into the cells. Only the active X47 (XA) virus replicated completely in Daudi cells and produced new viral particles by budding. The formalin-treated X47 virus did not damage or change the cells, and although the viral particles remained adsorbed to the cells, there was little penetration. The heat inactivated X47 virus (which was the most effective, non-virulent, oncolytic agent we studied) was visualized as large aggregates of particles adsorbed to the cell surface by electron microscopy. The cells themselves formed clumps. The viral aggregation and cell clumping likely resulted from the loss of viral neuraminidase activity due to heat treatment. The penetration of heat-inactivated viral particles was massive and involved numerous particles. Production of new viral particles was not demonstrated in this study even though nucleocapsids from the original virus were found in the cytoplasm. Thus, it appears that the massive penetration of the viral particles into cells damages the plasma membrane and may be responsible for the oncolytic potential of the heat-inactivated virus on Daudi cells.

Burkitt Lymphoma↗

Prevalence of antibodies to respiratory syncytial virus in various populations in Israel.

A preliminary study on the prevalence of antibodies to respiratory syncytial virus (RSV) in individuals of various age-groups was carried out. In healthy infants aged 6 to 12 months, the prevalence was 27%. It increased to 37 and 54% in children aged 1 to 2 and 2 to 4 years, respectively. The prevalence reached 78% in healthy individuals who were more than 20 years old, including pregnant women. Significant levels of specific antibodies were detected in 59% of children aged 6 to 12 months who were hospitalized with respiratory tract illnesses. It appears that acquisition of antibodies to RSV in our population occurs relatively later in life than in other Western countries.

Adolescent↗

Sensitivity of oral tissues to herpes simplex virus--in vitro.

Epithelial and fibroblast cells from the human gingival sulcus area were cultivated in vitro, and their sensitivity to the herpes simplex virus (HSV) was studied. Fibroblasts were sensitive to HSV infection and supported virus multiplication as evidenced by nuclear inclusion bodies and a cytopathogenic effect. Epithelial cells which were primarily devoid of HSV antigens were infected with HSV as demonstrated by positive immunofluorescent staining and damage to the cells at a later stage. Epithelial cells that were found to harbor HSV antigens upon removal from the patients prior to infection in vitro, maintained these antigens throughout the period of in vitro cultivation. The sensitivity of both epithelial cells and fibroblasts from the gingival sulcus area to HSV infection in vitro is significant for the understanding of the role of these tissues as a primary site of infection and as a possible reservoir for the latent virus between recurrences.

Antigens, Viral↗

Cellular response in humans following vaccination with Gripax influenza virus.

Cellular response of peripheral blood lymphocytes to influenza antigens was measured in a group of young nurse-student volunteers (17-24 years old), following vaccination with a formol-inactivated trivalent influenza vaccine (Gripax). Cord blood lymphocytes (controls) did not react with any of the antigens. This excluded the possibility of any nonspecific mitogenicity of viral antigens. Viability of the cells was indicated by their responsiveness to phytohemagglutinin (PHA). Prior to immunization antigenic recognition to circulating strains (A/England (H3N2) and B/Hong Kong) was found in about 44% of the vaccinees; recognition of the recent strain A/USSR (H1N1) was found in only 10.5%. Following vaccination, approximately 80% of the subjects exhibited cellular response to all three vaccine strains. This includes the negative subjects, who showed an approximate 70% rate of conversion. There was no correlation between the antibody state and cellular response prior to and following vaccination as gathered from matched data of each participant.

Adolescent↗

Antibodies to herpes simplex virus in human gingival fluid.

Antibodies to herpes simplex virus were found by immunofluorescent techniques in the gingival fluid of 84.0% of the persons tested. A mixture of IgG and IgA antibodies was demonstrated in 52.3% of the specimens while in 47.7% only IgG antibodies were found. Neutralization of herpes simplex virus infection in Vero cells by the gingival fluid was also demonstrated. No correlation between recurrences of herpes infection and the type of antibodies produced could be established.

Adult↗

A sensitive plaque inhibition technique for assay of antibodies to influenza virus: use to detect previous antigenic priming with influenza viruses.

Plaque reduction test performed in MDCK cells was found to be a more sensitive assay than hemagglutination inhibition, for revealing previous immunological experience with influenza A virus in the population. Based on the preimmunization antibody levels, determined by plaque reduction tests, it was possible to distinguish between previously primed and unprimed subjects among vaccinees.

Adolescent↗

Modulation of the lung local immune response by systemic immunization.

The present study describes the respiratory immune response of mice to locally administered antigen, and the modulation of this response by systemic immunization. Intranasal immunization of mice with the A/PR/8/34 strain of influenza virus evoked local antibody response of the IgA type. The titer of the IgA antibodies declined to a nondetectable level in 40--50 days. If at that time a second intranasal dose was administered, a secondary IgA response was evoked. On the other hand, administration by the intramuscular route resulted in a mixed population of IgA and IgG antibodies. The relevance of this finding to problems of immunization against respiratory viral infections is discussed.

Administration, Intranasal↗