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Biomedical subjects

J Shoham

Publications and source records attributed to J Shoham.

At least 37 records · Page 2Linked to original sources
PubMed1989

Enhancement of human monocyte cytotoxicity by both interferon-gamma and -beta and comparison to other stimuli.

Recombinant interferon preparations caused a dose-dependent increase of human monocyte cytotoxicity to the K562 and Daudi cell lines. Both rIFN-gamma and rIFN-beta enhanced this function to a similar extent, while rIFN-alpha c had less effect when compared on the basis of their anti-viral effects. Endotoxin and concanavalin A increased basal monocyte cytotoxicity while phagocytosis of latex particles had no effect. The increased monocyte cytotoxic effect of rIFN-beta was completely abrogated by monoclonal antibody to IFN-beta, while monoclonal antibody to IFN-gamma had no effect. However, monoclonal antibody to IFN-gamma only reduced the increased cytotoxic effect caused by rIFN-gamma by 25%. Catalase inhibited both basal monocyte cytotoxicity and the increase in cytotoxicity following addition of rIFN-gamma only slightly, suggesting that mechanisms other than the oxidative burst were active and could be induced by rIFN-gamma.

Antibodies, Monoclonal↗
PubMed1989

Contact-mediated maturational effects of thymic stromal cells on murine thymocytes in culture.

The effect of direct contact between thymic stromal cells and thymocytes on differentiation markers and functions of the latter was studied. The thymic stromal cells included two epithelial and one fibroblast cell lines, previously described. Murine thymocytes were incubated with confluent monolayers of these cells or their supernatants for 24 hr, using monolayers of non-thymic cells and their supernatants as controls. Then, the thymocytes were tested for changes in expression of several surface antigens [Thy-1, Lyt-1, Lyt-2, L3T4, IL-2-receptor (IL-2R)], spontaneous [3H]thymidine incorporation (STI), lectin-induced proliferative response (PR) and lymphokine (IL-2 and IL-3) production. All three thymic stromal cell lines reduced the expression of Thy-1, Lyt-1 and Lyt-2 significantly. The expression of L3T4 was also reduced in some of the experiments, while IL-2R was not expressed by the thymocytes, neither before nor after the co-culture. The thymic stromal cell lines also increased the spontaneous [3H]thymidine incorporation and lymphokine production by the thymocytes and inhibited their proliferative response to lectins. Under the same experimental conditions, the culture supernatants of the thymic stromal cells and the non-thymic cells did not have any effect on the thymocytes, either when collected and used separately or when used in a co-culture system which allowed thymocyte contact with the medium but not with the stromal cells (Transwell system). These results suggest a specific effect of thymic stromal cells, epithelial as well as fibroblasts, on thymocyte maturation. The effect is mediated by direct cell contact and not by secreted factors.

Animals↗
PubMed1988

Placebo-controlled trial of topical interferon in labial and genital herpes.

The efficacy of topical interferon-beta (IFN-beta) treatment was assessed in 25 patients with herpes of the lips or genitals who completed a 2-year follow-up in a double-blind placebo-controlled trial. IFN-beta gel (10(5) U/g) 4 times daily (about 2 x 10(4) U) applied locally during eruptions (about 10 days) reduced the mean number of recurrences (p less than 0.007) and the duration of eruptions (p less than 0.007): in the placebo group these indices did not change significantly. Reduction of symptoms and severity was noted in 11 of 12 patients on IFN-beta and in only 1 on placebo. No important side-effects were recorded. Topical IFN-beta may therefore be advantageous as a time-limited local treatment of recurrent herpes simplex virus infections of the genitals and lips.

Administration, Topical↗
PubMed1987

Antigen-stimulated lymphokines from patients with cutaneous leishmaniasis induce monocyte killing of Leishmania major intracellular amastigotes.

The specific immune response of patients with cutaneous leishmaniasis including the ability of their lymphokines to enhance the monocytes' leishmaniacidal activity was studied. In 16 patients with cutaneous leishmaniasis, their concanavalin A-induced lymphocyte proliferative responses, interferon-gamma and interleukin 2 activities and the ability of their concanavalin A-induced lymphokines to kill monocyte intracellular amastigotes were not different from normal controls. Antigen-stimulated lymphocyte cultures showed that 13 of 13 patients had an increased lymphocyte proliferative response; 11 of 16 produced interleukin 2 and 12 of 13 produced interferon-gamma; in addition, 10 of 11 of these antigen-induced supernatants increased the monocytes' killing of Leishmania major amastigotes. Antibody levels to parasite membrane antigens determined by radioimmunoassay showed that 8 of 13 titers were greater than 10 and 4 of 13 titers were 2 to 10 times higher than control. Our findings demonstrate that patients with cutaneous leishmaniasis elicit a specific immune response to L. major antigens and part of this response is the production of lymphokine capable of promoting monocyte killing of intracellular amastigotes.

Animals↗
PubMed1987

Modulation of immune response and tumor development in tumor-bearing mice treated by the thymic factor thymostimulin.

Thymostimulin (TS), a partially purified thymic factor, has a significant impact on tumor development in C57B1/6 mice inoculated with Lewis lung carcinoma (3LL) cells, as judged by its effect on time of tumor appearance after tumor cell transplantation. In a previous study, we determined the conditions under which survival rate of the tumor-bearing mice can be significantly increased by TS treatment. In the study communicated here we analyzed host defense mechanisms that are modified by TS treatment in the tumor-bearing mice. In general, immune parameters that were increased or stimulated by the presence of the tumor were further increased in the TS-treated animals (number of lymphoid spleen cells, their response in mixed lymphocyte tumor cultures, their natural killer cell activity, and their ability to produce colony-stimulating factor), or reached earlier maximum levels (spontaneous [3H]thymidine incorporation, a reflection of in vivo spleen cell activation). Responses which reflect tumor-induced immunosuppression (proliferative response induced by phytohemagglutinin or concanavalin A stimulation) were restored to normal level by TS. Specific tumor-related reactions (specific cell-mediated cytotoxicity) were preserved in the TS-treated animals. The wide spectrum of TS effects had, nevertheless, certain elements of selectivity; e.g. colony-stimulating factor, but no interferon production is enhanced by TS in the tumor-bearing mice in diametric contrast to TS effect in Mengo virus-infected mice. The spectrum of TS effects was also dependent on the type of tumor cell used. The results indicate that the significant effect of TS on 3LL tumor development in mice is associated with a strong, multifaceted effect of TS on the immune system.

Animals↗
PubMed1987

Solid-phase radioimmunoassay for the measurement of surface antigens expressed on intact lymphocytes.

A solid-phase radioimmunoassay was developed for the measurement of lymphocyte surface antigens. The assay was performed in microplates, using cells that were initially fixed to the wells by air drying. The method was used for the measurement of Thy-1, Lyt-1,2,3, IL-2-R, H-2Kb and DR antigens on the surface of mouse thymus, spleen and bone marrow cells, mouse cell lines CTLL, EL-4 and DA-1 and human thymocytes and consisted of sequential incubations with rat or mouse monoclonal antibodies directed against the above antigens, rabbit anti-rat or goat anti-mouse IgG and 125I-protein A. The assay permits the processing of large numbers of samples, is easy to perform, reliable and highly specific.

Animals↗
PubMed1987

Topical application of human fibroblast interferon (IFN) in cutaneous leishmaniasis.

Fifteen patients with single or multiple lesions of cutaneous leishmaniasis were randomly assigned to apply either IFN-beta-containing cream or a placebo cream base. Despite 8 weeks of therapy no significant improvement of the lesions was achieved. Although topical IFN-beta was not effective in this study, several laboratory studies suggest that IFN, particularly IFN-gamma, may be of therapeutic value in cutaneous leishmaniasis.

Administration, Topical↗
PubMed1986

The enhancing effect of interferon-beta and -gamma on the killing of Leishmania tropica major in human mononuclear phagocytes in vitro.

Both native human IFN-beta or -gamma added to human monocytes in culture increased their leishmaniacidal effect on intracellular Leishmania tropica major (L. major) amastigotes. This effect was dose-dependent, and was apparent if the IFN was added either before or after infection of the monocyte cultures with the promastigote form of the parasite. Compared on the basis of antiviral activity, IFN-gamma was shown to have a leishmaniacidal effect approximately three times greater than IFN-beta. Recombinant IFN preparations showed similar effects. In addition, IFN-gamma increased H2O2 production from human monocytes in culture in a dose-dependent manner. Monoclonal antibody to IFN-gamma abrogated both its effect on the leishmaniacidal capacity and on H2O2 production by the monocytes. These results suggest that IFN-gamma may be of therapeutic value in cutaneous leishmaniasis.

Adjuvants, Immunologic↗
PubMed1986

The effects of Con A-induced lymphokines from the T-lymphocyte subpopulations on human monocyte leishmanicidal capacity and H2O2 production.

The effects of concanavilin A (Con A)-induced lymphokines from human peripheral blood mononuclear cells, enriched helper and suppressor lymphocyte populations and recombinant interferon-gamma (IFN-gamma) on the ability of monocytes to promote killing of intracellular Leishmania major (L. major) amastigotes and to induce the production of hydrogen peroxide (H2O2) was examined. All these mitogen-induced supernatants contained active IFN-gamma. There were no differences in the ability of these supernatants or IFN-gamma to promote the monocyte killing of the L. major amastigotes or H2O2 production. An increase in H2O2 production by monocyte monolayers was observed following the addition of either of these supernatants or IFN-gamma alone. In addition, a marked increase in the production of H2O2 was observed following priming with either of these mitogen-induced supernatants or IFN-gamma and the addition of a second stimulus, phorbol myristate acetate (PMA). Monoclonal antibody to IFN-gamma abrogated the increase in production of H2O2 by all these mitogen-induced supernatants; however, this antibody only resulted in partial inhibition of the leishmaniacidal effect of these lymphokines on human monocytes. These results would suggest that IFN-gamma is the component of the lymphokine that is largely or exclusively responsible for H2O2 production, while other factors in addition to IFN-gamma are important in promoting oxygen-independent mechanisms for the killing of intracellular L. major amastigotes.

Cells, Cultured↗
PubMed1985

Rapid improvement in a terminal case of hairy cell leukemia treated with a new human recombinant interferon, IFN-alpha-C.

A new type of human interferon (IFN), IFN-alpha-C, produced in Escherichia coli and purified on monoclonal antibodies, was given at a dose of 3 X 10(6) u (3 micrograms)/day to a terminally ill unsplenectomized patient with hairy cell leukemia, who had had severe recurrent infections and pancytopenia. There was marked reduction in the size of the spleen after 2 weeks, and platelet counts returned to normal after 1 month of treatment. The IFN treatment also raised the granulocyte counts and hemoglobin levels, improved the normal repopulation of the bone marrow, and restored resistance to infections. IFN-alpha-C was well tolerated, without serious side effects, and treatment has been continued for 10 months.

Cytotoxicity Tests, Immunologic↗
PubMed1984

An immunoenzyme quantitative assay for the antiviral effect of interferons.

A technique is described for measurement of the antiviral activity of interferon by an immunoenzymatic assay for viral proteins. Cells treated by tested samples of interferon (IFN) are infected with vesicular stomatitis virus (VSV) and following the development of viral cytopathy are lysed by the addition of deoxycholate and then transferred into ELISA microplates. The viral proteins bind effectively to the microplates proportionally to their level in the culture and may be measured by incubating the plates sequentially with (1) rabbit antiserum against VSV, (2) a conjugate of alkaline phosphatase either to protein A or to an antibody against rabbit IgG and (3) p-nitrophenylphosphate. This procedure may be further simplified by using antibodies against VSV to which alkaline phosphatase has been directly conjugated. We found this immunoenzyme assay to be superior to the 'cytopathic effect inhibition' assay in precision and sensitivity and in being independent of the effectiveness of viral cytopathy.

Adsorption↗
PubMed1984

Intramuscular human interferon-beta injections in treatment of condylomata acuminata.

A two-part study was done to assess the value of human fibroblast interferon (IFN-beta) in the treatment of condylomata acuminata. The first part was an open study of different IFN-beta preparations, which showed that intramuscular injection was the most suitable mode of administration of IFN-beta. In the double-blind placebo section 22 patients were given injections of 2 X 10(6) units IFN-beta or placebo for 10 consecutive days and followed up for 3 months. In 9 of the 11 in the IFN-beta group and 2 in the placebo group lesions disappeared from about 5 weeks after completion of the course of injections. After 3 months 8 of the non-responders were given a course of IFN-beta and all responded to treatment. None of those who had responded has had a recurrence, the disease-free period now being 12 months. Changes in (2'-5')oligo A synthetase levels in white blood cells confirm that intramuscular injections of IFN-beta produce a systemic response.

2',5'-Oligoadenylate Synthetase↗
PubMed1984

Antiviral activity of a thymic factor in experimental viral infections. I. Thymic hormonal effect on survival, interferon production and NK cell activity in Mengo virus-infected mice.

A partially purified thymic factor, thymostimulin (TS), significantly increased the survival rate of adult, immune-intact mice infected with the neurotropic Mengo virus. TS treatment was begun after virus inoculation by daily i.p. injections. In untreated C57BL/6 mice, LD50 was reached with 1 X 10(4) PFU, but 10-fold more virus (i.e., 1 X 10(5) PFU) was needed to reach LD50 in TS-treated animals. TS effect on survival, though, could be observed with several virus doses (1 X 10(3) to 1 X 10(6) PFU) (p less than 0.001). A significant effect on survival was also observed with outbred ICR mice (p less than 0.005). Serum interferon (IFN) levels in the Mengo virus-infected mice were relatively low (average peak 300 U/ml), but were significantly increased (two- to ninefold) in the TS-treated mice. Peak serum levels were reached earlier in TS than in control animals (24 hr and 72 hr, respectively). Both acid-labile and acid-stable type I IFN production were augmented by TS in the Mengo virus-infected mice. Natural killer activity was also enhanced by TS, in particular on the second day after virus inoculation. In addition, MP-virus was used as a second, unrelated virus challenge. This virus caused a nonlethal infection, with relatively high levels of serum IFN (average peak 10,000 U/ml). TS increased IFN levels (two- to eight-fold) also in this challenge system. In conclusion, TS causes a nonspecific enhancement of endogenous production of IFN and has a significant effect on the survival of lethally infected mice. The data indicate a potential application of thymic factors for the treatment of viral infections.

Animals↗
PubMed1984

Thymic hormonal effect on recovery from early and late CCNU induced immunosuppression.

The alkylating agent 1(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) caused a prolonged suppression of antibody response to sheep red blood cell challenge in mice. Two phases of suppression could be observed, an early (first three weeks after CCNU administration) and late phase (4-10 weeks). The late immunosuppression was more severe than the early one. Treatment by the thymic extract thymostimulin (TP-1R) caused a complete recovery of antibody response, with overshoot, during early phase, but only partial recovery during late phase. It is suggested that the known CCNU induced damage to stem cells, manifested at late phase, reduces the responding pool for the restorative effect of thymostimulin.

Animals↗
PubMed1984

Postsurgical adjuvant treatment of malignant melanoma patients by the thymic factor thymostimulin.

37 patients with cutaneous malignant melanoma (MM) were randomized, after surgical removal of tumor, to either no further treatment or to adjuvant treatment by the thymic factor thymostimulin (TS; Tp-1 Serono). 26 patients were with primary (stage I) MM (tumor thickness greater than 1.25 mm), and 11 patients with local or regional disease spread (stage II MM). Randomization was done separately for each disease stage. Life table analysis of the results indicates that significantly (p less than 0.01) more patients were free of disease at one year on study if treated by TS than if left untreated. Probability of survival was also better (p = 0.05) in the TS-treated group at 15 months on study. No side effects, toxic or allergic, were observed under TS treatment.

Adult↗
PubMed1983

Thymic hormonal activity on human peripheral blood lymphocytes, in vitro. IV. Proliferative response to allogeneic tumor cells in healthy adults and cancer patients.

A mixed lymphocyte tumor culture (MLTC) assay was used in order to assess thymic hormonal activity on human T-lymphocyte function. Peripheral blood mononuclear cells (PBMC) from 55 healthy subjects and 54 immunodeficient cancer patients were incubated with the thymic extract TP-1, cultured with allogeneic tumor cells (Raji lymphoma or IgR3 melanoma cells) under limiting stimulation conditions and their proliferative response measured by 3H-thymidine incorporation. Mean proliferative response in the cancer group was lower than in the healthy group. TP-1 caused a significant enhancement of mean proliferative response, comparable in the healthy and cancer groups, under all the conditions tested. Analysis of response in the individual cases disclosed a wide scatter of TP-1 effects, including some cases of TP-1 induced suppression. A significant negative correlation between TP-1 effect and level of proliferative response in control was found: enhancement of proliferative response by TP-1 became progressively greater as control proliferative response became progressively lower. A similar pattern was noticed in the cases of TP-1 induced suppression. The negative correlation was similar for the healthy and cancer groups. These results cannot be interpreted in terms of restoration of deficient immune functions, but are compatible with an indirect, regulatory effect of TP-1 on proliferative response, exerted to a comparable degree in the healthy and immunodeficient situations. The possibility that thymic factors regulate normal immune functions, not merely restore deficient functions to normal, may have interesting clinical implications.

Cell Division↗
PubMed1983

Thymic hormonal activity on human peripheral blood lymphocytes, in vitro. V. Effect on induction of lymphocytotoxicity.

Thymic hormonal effect on lymphocytotoxicity induced in vitro and its target specificity were tested using peripheral blood mononuclear cells (PBMC) of healthy subjects. PBMC were treated by the thymic extract TP-1, a similarly prepared spleen extract (SE) or medium only (1 h, 37 degrees C) and then induced to express cytotoxic activity by exposure to allogeneic tumor cells in mixed cultures or by Con A stimulation. The cytotoxicity developed after several days in culture was assayed on 51Cr labelled tumor cells. TP-1 caused a significant mean enhancement of cytotoxicity induced and assayed on Raji lymphoma cells (mean % specific lysis, 31.5 +/- 2.9 without TP-1 and 53.7 +/- 3.6 with TP-1; n = 42; p less than 0.01). The scatter of individual responses to TP-1 was wide, however, and included also some cases of TP-1 induced suppression. Similar wide scatter of TP-1 effects with emphasis on TP-1 induced enhancement was observed with other tumor cell lines or with Con A as inducers. Usually, SE had no effect on induced cytotoxicity. Target selectivity (specificity) of induced cytotoxicity was tested by induction and assay on several tumor cell lines with crossing over, as well as by cold competition assay. When target selectivity was present, it was not masked by TP-1 induced enhancement. Moreover, in some cases, target selectivity became more pronounced after TP-1 treatment. However, TP-1 enhanced also Con A induced non-specific cytotoxicity. No effect of TP-1 on natural killer cell activity of fresh PBMC could be demonstrated. It is suggested that both selective cytotoxicity (T-cell dependent) and non-selective one maybe modulated directly by TP-1 and indirectly by TP-1 modified secondary interactions in culture. This profound regulatory effects could be demonstrated in the PBMC of immune-intact healthy adults.

Cell Line↗