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S Slavin

Publications and source records attributed to S Slavin.

At least 235 records · Page 13Linked to original sources
PubMed1991

Immunoglobulins A, G, and M to cytomegalovirus during recurrent infection in recipients of allogeneic bone marrow transplantation.

Occurrence and significance of specific IgA and IgM to cytomegalovirus (CMV) in recurrent CMV infection was evaluated in 21 allogeneic T lymphocyte-depleted bone marrow transplantation (BMT) recipients who had been previously CMV seropositive. Of 17 patients with CMV infection, viruria was detected in 94%, CMV-specific IgA in 88% and IgM in 76%, and a fourfold rise in IgG in 65%. The median time between BMT and detection of viruria was 69 days, of IgA 70, of IgM 62, and of IgG 88 days. The IgM and IgA responses lasted for 14 and 30 days (median time), whereas high IgG titers persisted. Twelve patients developed CMV disease; in these the appearance of viruria, IgA, and IgM preceded the rise of IgG (P less than .02). CMV-specific IgA and IgM are valuable diagnostic tools in BMT recipients with recurrent CMV infection.

Adolescent↗
PubMed1991

New developments in bone marrow transplantation.

A better understanding of the immunobiology after transplantation and of the available recombinant cytokines that enhance hematopoietic reconstitution following autologous and allogeneic bone marrow transplantation is likely to result in safer application of bone marrow transplantation. Residual tumor cells escaping chemotherapy or chemoradiotherapy given in the course of autologous and allogeneic bone marrow transplantation are still a barrier to complete eradication of malignancy. Recent experiments in animal models of human disease suggest that minimal residual disease can be controlled by an innovative therapy consisting of the administration of cytokines such as recombinant human interleukin-2 and interferon-alpha. Moreover, graft versus leukemia-like effects are induced in conjunction with autologous and allogeneic bone marrow transplantation by administration of allogeneic immunocompetent lymphocytes and recombinant interleukin-2 following bone marrow transplantation and especially by combined administration of allogeneic lymphocytes and recombinant interleukin-2. Similar approaches are currently being investigated in humans with encouraging preliminary results. Overall, our data suggest that eradication of the last tumor cell is neither feasible nor necessary for achieving operational cure. Control of minimal residual disease by activation of anticancer effector cells today seems closer than ever and we are optimistic that further advances in immunotherapy will be applicable to clinical practice in the near future.

Animals↗
PubMed1991

Recombinant human superoxide dismutases: production and potential therapeutical uses.

In many pathological situations, tissue damage is caused by cellular generation of superoxide free radicals (O2-). These active species are generated during post-ischemic reperfusion of organs, in hyperoxic tissue, during acute and chronic inflammation and during exposure to ionizing radiation. Exogenous superoxide dismutase (SOD) was shown to significantly prevent such damage. The genes for human cytosolic Cu/ZnSOD and mitochondrial MnSOD were cloned and introduced into an E. coli expression system. The proteins were expressed in high yields and purified to homogeneity, yielding pharmaceutical-grade materials. These enzymes were used in a variety of in vivo animal models for the demonstration of their protective effects against oxidative damage. Comparative pharmacokinetic studies in rats have revealed that the half-life of Cu/ZnSOD was 6-10 min., while that of MnSOD was 5-6 hours, thus indicating that MnSOD may be superior to Cu/ZnSOD for the treatment of chronic diseases. Indeed, MnSOD was found to be effective as an anti-inflammatory agent in the rat carrageenan induced paw edema acute inflammation model. Both enzymes were also effective in ameliorating post-irradiation damage in mice exposed to whole-body or localized chest X-ray radiation.

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

Immune response to polio vaccination in bone marrow transplant recipients.

Following a small outbreak of poliomyelitis which occurred in the summer of 1988 in Israel, two sequential doses of inactivated polio vaccine (IPV) were administered to 42 bone marrow transplant (BMT) recipients (aged 2-50 years) who were 6-96 months (median 16 months) after transplantation. Prior to vaccination, only 68-80% patients (n = 42) had protective (greater than or equal to 4) antibody levels against the three serotypes of poliovirus, compared with 92-96% (n = 25) before BMT (p = 0.02 for types 1 and 3). After the second dose of IPV, 89-98% (n = 27) of the recipients had protective antibody levels. The pre-vaccination antibody titers were lower than before BMT (p = 0.006, 0.0007 and 0.0008 for types 1,2 and 3, respectively). After the first dose of IPV, antibody titers rose in the 42 patients (p = 0.002, 0.043 and 0.002 for types 1, 2 and 3, respectively) and following the second dose, a further increase in antibody levels was noted. Regression analysis revealed that graft-versus-host disease, pre-BMT polio antibody titers, age and type of transplantation (allogeneic versus autologous) were significant explanatory variables for the specific antibody levels, while the time lapse between BMT and vaccination, and primary disease proved of no significance. Vaccination against poliovirus after BMT is advocated, as it reinstates and raises the lost specific humoral immunity.

Adolescent↗
PubMed1991

Effect of exogenous recombinant human granulocyte and granulocyte-macrophage colony-stimulating factor on neutrophil function following allogeneic bone marrow transplantation.

Functional activity of peripheral blood granulocytes was assessed in seven patients and in their normal donors following allogeneic bone marrow transplantation (BMT). Functions studied included superoxide generation (O2-), intracellular killing of Staphylococcus aureus, phagocytosis, and killing of Candida albicans. Neutrophils were tested following preincubation with 300 pM granulocyte-macrophage colony-stimulating factor (GM-CSF), 1.2 nM granulocyte colony-stimulating factor (G-CSF), or buffered solution (diluent) as control. Our data indicate that following BMT, both recipients and their normal donors show GM-CSF- and G-CSF-induced increases in: 1) O2- production in response to fMet-Leu-Phe (fMLP), 2) killing of S. aureus, and 3) phagocytosis of C. albicans. In two patients that showed low candidacidal activity, GM-CSF and G-CSF markedly enhanced the cytotoxic activity of the cells. Our studies indicate that GM-CSF and G-CSF increase "oxygen-dependent" oxidative activities in neutrophils from BMT recipients and their normal donors and enhance the antimicrobial activity of the cells.

Adult↗
PubMed1991

Transient elevation of serum lactic dehydrogenase following autologous bone marrow transplantation.

Transient elevated levels of serum lactic dehydrogenase (LDH) were reported immediately following autologous bone marrow transplantation consecutively in 15 patients. Isoenzyme 2 was the predominant elevated isoenzyme of LDH, suggesting that the source of LDH is either hemolysis of RBCs, which occurs during freezing and thawing of bone marrow in the bags and in vivo following infusion of residual dimethyl sulfoxide.

Adolescent↗
PubMed1991

The effect of in vitro T lymphocyte depletion on generation of IL2-activated cytotoxic cells.

The effect of immunocompetent lymphocyte depletion on precursors and effector cells of IL2 activated non-MHC restricted cytotoxic cells (LAK) generated from bone marrow (BM) or peripheral blood was investigated. Lymphocyte depletion was carried out by using Campath-1, a monoclonal rat anti-human lymphocyte antibody recognizing CDW52, that binds human complement and is used routinely in clinical bone marrow transplantation (BMT). The results indicate that LAK precursors derived from BM cells are sensitive to Campath-1 treatment, while a variable degree of sensitivity was demonstrated in LAK precursor cells derived from peripheral blood. In contrast, effector LAK cells generated in vitro were shown to be resistant to treatment with Campath-1 and complement. We hypothesize that if indeed IL2-dependent non-MHC restricted cytotoxic cells play a role in vivo in the immediate post-BMT period, a T lymphocyte depletion procedure such as the Campath-1 may have the capacity to reduce, at least temporarily, the graft-versus leukemia effects mediated by such anti-tumor effector mechanisms.

Animals↗
PubMed1990

The use of parabiosis for investigating the mechanism of transplantation tolerance in bone marrow chimeras induced by total lymphoid irradiation.

The mechanism of transplantation tolerance in total lymphoid irradiation (TLI)-induced semiallogeneic bone marrow chimeras without clinical evidence of graft-versus-host disease (GVHD) was investigated using the technique of surgical parabiosis. When held in parabiosis with normal BALB/c mice, BALB/c---- (BALB/c x C57BL/6)F1 (BALB----F1) chimeras survived 7-9 days, significantly (P less than 0.001) shorter than the 12-19 day survival of normal F1 hybrids kept in parabiosis with normal BALB, and in contrast to indefinite (greater than 200 days) survival of syngeneic BALB parabiotic partners. When C57 skin grafts were placed on BALB mice held in parabiosis with BALB----F1 chimeras, C57 skin grafts survived 50-60 days, in contrast to 10-14 days in normal BALB recipients (P less than 0.001). Lethal GVHD, induced in sublethally irradiated F1 recipients by 10(7) BALB spleen cells, could not be delayed or prevented by cotransfer of 10(7) to 30 x 10(7) tolerant BALB spleen cells obtained from stable BALB----F1 chimeras. GVHD reactivity of BALB spleen cells isolated from BALB----F1 chimeras tolerant of C57 could not be recovered by depletion of Lyt2 cytotoxic suppressor cells. Taken together, in the absence of suppressive capacity by suppressor cells, these data support functional clonal deletion as the primary mechanism responsible for the maintenance of unresponsiveness to host alloantigens in TLI-induced semiallogeneic chimeras, since no protection against induction of GVHD could be documented in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Characterization of effector cells of graft vs leukemia following allogeneic bone marrow transplantation in mice inoculated with murine B-cell leukemia.

It is now widely accepted that immunocompetent lymphocytes in allogeneic bone marrow grafts exert an antileukemic effect that contributes to the cure of leukemia. Graft vs leukemia (GVL) effects independent of graft vs host disease were investigated in allogeneic bone marrow chimeras tolerant of host and donor alloantigens. The role of Thy1.2, L3T4 and Lyt2 T lymphocytes as effector cells of GVL were investigated in (BALB/c x C57BL/6)F1 mice inoculated with murine B-cell leukemia and subsequently conditioned with total lymphoid irradiation and cyclophosphamide (200 mg/kg). Mice were reconstituted with C57BL/6 bone marrow cells depleted of well-defined T-cell subsets or enriched for stem cells by the soybean agglutination method. Detection of residual tumor cells, an indicator for efficacy of GVL, was carried out by adoptive transfer of peripheral blood or spleen cells obtained from treated chimeras into secondary naive BALB/c recipients at different time intervals following bone marrow transplantation. Treatment of the primary marrow inoculum with monoclonal anti-Thy1.2 or anti-Lyt2 abolished the GVL effects and all secondary BALB/c recipients developed leukemia within 60 days. On the other hand, the treatment with monoclonal anti-L3T4 did not influence the effect of GVL and all treated recipients remained without leukemia. The data suggest that T cells may mediate GVL effects in the absence of graft vs host disease and in circumstances where tolerance to conventional alloantigens is elicited. Effector cells of GVL across the major histocompatibility complex (MHC) in the murine B-cell leukemia tumor model system appear to be Thy1.2+ Lyt2+ L3T4-. Induction of GVL effects by allogeneic cells tolerant of host MHC suggests that these effects may be independent of graft vs host disease.

Agglutinins↗
PubMed1990

Interstitial pneumonitis after total body irradiation: effect of partial lung shielding.

The potential beneficial effects of partial lung shielding were investigated in 44 patients conditioned by whole body radiotherapy as part of the conditioning for bone marrow transplantation (BMT). The first 23 patients were irradiated with fractionated total body irradiation (TBI) to a total dose of 12 Gy. In the second series of 21 patients a 50% transmission lung shield was utilized following 6 Gy TBI. This treatment was combined in the second group with four fractions of 1.5 Gy total lymphoid irradiation (TLI), given in 2 d. The rate of idiopathic interstitial pneumonitis (IP) was 26% in the first group, compared to none in the second.

Adolescent↗
PubMed1990

Effect of cyclosporine A and methylprednisolone on the graft-versus-leukemia effects across major histocompatibility barriers in mice following allogeneic bone marrow transplantation.

The effect of post-transplant immunosuppressive agents used in anti-GVHD prophylaxis on leukemic relapse was tested using a murine model of originally spontaneous, subsequently transplantable and non-immunogenic B cell leukemia (BCL1). (BALB/c x C57BL/6)F1 mice inoculated with 10(7) BCL1 cells were conditioned by total lymphoid irradiation (TLI) (1600 cGy), cyclophosphamide (200 mg/kg) or total body irradiation (TBI) 750 cGy and reconstituted with C57BL/6 (C57) bone marrow cells (30 x 10(6] or 10 x 10(6) bone marrow cells with additional 2 x 10(6) donor-type spleen cells, respectively. Mice were treated by cyclosporine A (CSA) 20 mg/kg i.p., or methylprednisolone (MP) 10 mg/kg i.p. for 10 days each and one group of controls received no post-transplant therapy. Stable chimerism was documented in all recipients with greater than or equal to 90% donor-type C57 cells in the peripheral blood. Eighty-nine percent of the mice treated by CSA following conditioning with TLI developed leukemia within 70 days, whereas none of the MP-treated mice and none of untreated chimeras showed any evidence of leukemia for more than 150 days. Adoptive transfer experiments using 10(5) spleen cells obtained from recipients conditioned with TBI were done to monitor residual leukemic cells following different post-transplant treatments. Eight-five percent of recipients of spleen cells obtained from mice treated with CSA developed leukemia in contrast with 33% and 25% when spleen cells were obtained from mice treated with MP or untreated controls, respectively (p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

The use of recombinant cytokines for enhancing immunohematopoietic reconstitution following bone marrow transplantation. II. The influence of lymphokines on CFU-GM colonies from human untreated, ASTA-Z or Campath-1M treated bone marrow.

Patients undergoing bone marrow transplantation (BMT) are subjected to the risk of pancytopenia in the immediate post-BMT period. Recipients of bone marrow (BM) autografts purged in vitro by chemical agents such as mafosfamide (ASTA-Z) are even more likely to develop a delayed engraftment. In a previous study in mice, we showed earlier immunohematopoietic reconstitution after syngeneic marrow grafting with BM cells precultured with single or combined cytokines. In this work we determined optimal culture conditions for the use of single and various cytokine combinations in order to activate progenitor cells following in vitro cultures of untreated, ASTA-Z purged or T cell-depleted human BM preparations prior to BMT. The best single cytokine for enhancing CFU-GM was found to be GM-CSF (0.1 mg/ml) which produced an increase of up to 8-fold over controls after 3 days' incubation. Addition of recombinant human interleukin 3 (rhIL3) (0.1 mg/ml) to rhGM-CSF had an additive effect. The same enhancing effect of in vitro CFU-GM by both cytokines was observed following ASTA-Z purging of BM cells obtained from patients undergoing autologous BMT. Similarly, depletion of lymphocytes from BM using the monoclonal rat anti-human lymphocyte antibody Campath-1M and human complement did not diminish the beneficial influence of rhIL3 and rhGM-CSF. When combined with rhGM-CSF and rhIL3, rhIL1 and rhIL2 had no appreciable enhancing effect on CFU-GM and occasionally even reduced it. We suggest that enhancement of differentiation of hematopoietic progenitor cells may be accomplished by in vitro incubation of BM cells without continuous administration of cytokines in vivo following BMT.

Antineoplastic Agents↗