Function of natural killer cells in immune defence against human leukaemia.

Although progress has been made in the management of acute leukaemias, most patients who fail to respond to front-line therapies with cytostatic agents and stem cell transplantation, or who relapse after an initial response die from progressive disease. Novel treatment modalities exploiting donor-derived natural killer (NK) cells generate an alloreactive graft-versus-leukaemia response and eliminate the residual malignant clones in transplanted patients. NK cells are components of the innate immunity playing an important role in the surveillance of human tumours. Recognition of malignant cells depends on a dynamic balance between antagonistic functions of an array of NK activating and inhibitory receptors. The natural cytotoxicity receptors (NCRs) are NK cell-specific and together with the NKG2D receptor are responsible for NK cell activation and tumour cell killing. The killer immunoglobulin-like receptors (KIRs) recruit phosphatases and can antagonise the activating signals and prevent the cytolytic NK cell programme. Understanding of the integration of these multiple signals at the molecular level is central for exploring the cytolytic function of NK cells. This review describes molecular mechanisms of NK receptor-ligand interactions controlling target cell recognition and addresses the potential of NK cells for the specific elimination of leukaemic clones with the goal of advancing immunotherapy of leukaemia.

Dietary transfer of fluoranthene from an estuarine oligochaete (Monopylephorus rubroniveus) to grass shrimp (Palaemonetes pugio): Influence of piperonyl butoxide.

The objective of this study was to determine the potential for dietary transfer of sediment-associated fluoranthene from tubificid oligochaetes (Monopylephorus rubroniveus) to grass shrimp (Palaemonetes pugio). Grass shrimp, either in the presence or absence of sublethal waterborne concentrations of the metabolic inhibitor, piperonyl butoxide (PBO), were fed fluoranthene-dosed oligochaetes for 5-days. All grass shrimp bioaccumulated fluoranthene; however, bioaccumulation was 3X higher in the presence of PBO. Trophic transfer coefficients (TTCs) were 0.02 and 0.01 in the presence and absence of PBO, respectively. Following the 5-day accumulation period, shrimp in both treatments were allowed to depurate for 3 days. Depuration rates were significantly higher in PBO-exposed shrimp. These results demonstrated that sediment-associated fluoranthene can be transferred through the diet from oligochaetes to grass shrimp, and the presence of PBO enhanced fluoranthene bioaccumulation. However, the comparatively low TTCs suggest that biomagnification of fluoranthene in estuarine food webs is low.

Activated natural killer cells from patients with acute myeloid leukemia are cytotoxic against autologous leukemic blasts in NOD/SCID mice.

Natural killer (NK) cells are implicated in the surveillance of hematological malignancies. They participate in the immune response against residual acute myeloid leukemia (AML) after hematopoietic stem cell transplantation with partial HLA class I disparity. However, the role of NK cells in autologous leukemia-specific immunity remains poorly understood. We studied the function of NK cells in AML patients at diagnosis. Following isolation, CD56+CD3- cells exhibited a high proliferative potential in vitro in response to interleukin (IL)-2. The polyclonal population of activated AML-NK cells expressed normal levels of the activating receptor NKG2D and the major natural cytotoxicity receptor NKp46. AML-NK cells were highly effective with respect to interferon-gamma production, cytotoxicity against HLA class I-deficient K562 erythroleukemia cells in vitro and retardation of tumor growth in vivo in K562-bearing NOD/SCID mice. Importantly, when AML blasts were injected into NOD/SCID mice, a single dose of adoptively transferred autologous AML-NK cells significantly reduced the AML load by 8-77%. Recognition of AML blasts may be related to the observed upregulation of ligands for NKG2D and natural cytotoxicity receptors in vivo. We conclude that AML patient-derived NK cells are fully functional, in support of exploring the benefit of AML immunotherapy with IL-2-stimulated autologous NK cells.

Function of natural killer cells in immune defence against human leukaemia.

Although progress has been made in the management of acute leukaemias, most patients who fail to respond to front-line therapies with cytostatic agents and stem cell transplantation, or who relapse after an initial response die from progressive disease. Novel treatment modalities exploiting donor-derived natural killer (NK) cells generate an alloreactive graft-versus-leukaemia response and eliminate the residual malignant clones in transplanted patients. NK cells are components of the innate immunity playing an important role in the surveillance of human tumours. Recognition of malignant cells depends on a dynamic balance between antagonistic functions of an array of NK activating and inhibitory receptors. The natural cytotoxicity receptors (NCRs) are NK cell-specific and together with the NKG2D receptor are responsible for NK cell activation and tumour cell killing. The killer immunoglobulin-like receptors (KIRs) recruit phosphatases and can antagonise the activating signals and prevent the cytolytic NK cell programme. Understanding of the integration of these multiple signals at the molecular level is central for exploring the cytolytic function of NK cells. This review describes molecular mechanisms of NK receptor-ligand interactions controlling target cell recognition and addresses the potential of NK cells for the specific elimination of leukaemic clones with the goal of advancing immunotherapy of leukaemia.

Ras oncogenes amplify lymphokine (interleukin 3, granulocyte-macrophage colony-stimulating factor) induction by calcium ionophore.

Interleukin 3 (IL-3) expression in PB-3c mastocytes is transiently induced in vitro by treatment with the drug A23187, a calcium ionophore, or constitutively following ras-dependent transformation in vivo. While the mechanism of oncogenically induced IL-3 expression is not clear, A23187-mediated lymphokine mRNA accumulation is primarily the result of calcium-dependent mRNA stabilization. We investigated whether the expression of various ras alleles influenced IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA induction by A23187. It was found that activated forms of ras potentiated ionophore-mediated lymphokine mRNA accumulation. This enhancement involves a post-transcriptional mechanism, as ionophore-induced lymphokine mRNAs are significantly more stable in ras oncogene-expressing lines than in the control line. We propose that one way by which ras genes exert their oncogenic potential is by extending the half-life of short-lived growth factor mRNAs.

Glycine-cysteine substitution at codon 13 of the N-ras proto-oncogene in a human T cell non-Hodgkin's lymphoma.

Tumor-derived DNA from a non-Hodgkin's (T cell) lymphoma patient, assayed by NIH3T3 transfection followed by inoculation of cells into nude mice, was found to contain an activated N-ras proto-oncogene. The mode of activation was determined by hybridization with N-ras-specific oligonucleotide probes detecting mutations at codons 12, 13 and 61. A transversion in codon 13 (GGT----TGT) resulting in replacement of glycine13 by cysteine13 in ras p21 protein was found. The mutation was detected in DNA from mouse tumors induced by transfected NIH3T3 cells and in DNA from patient tumor lymphoblasts. The patient was heterozygous for this mutation. These data identify the first base of codon 13 as a novel mutation site in ras genes and indicate that cysteine at position 13 of the ras p21 is a transforming substitution.

Effect of flt3 ligand on in vitro growth and expansion of colony-forming bone marrow cells from patients with aplastic anemia.

To determine the value of flt3 ligand (flt3L) in stimulating hematopoiesis in human hypoproliferative bone marrow disorders, we examined its in vitro effect on bone marrow cells from patients with aplastic anemia (AA). Growth response to flt3L, alone and in combination with other hematopoietic growth factors, was investigated in clonogenic methylcellulose assays, in long-term liquid and stroma cultures. Bone marrow cells were derived from 13 AA patients with persisting in vitro growth defect after immunosuppressive treatment and from nine normal bone marrow donors. In methylcellulose cultures, flt3L stimulated formation of hematopoietic colonies only weakly, whereas it had an additive effect when combined with erythropoietin (Epo), stem cell factor (SCF), interleukin-3 (IL-3), interleukin-11 (IL-11), or granulocyte colony-stimulating factor (G-CSF). Flt3L was less effective than SCF and did not further enhance the number of hematopoietic colonies formed in response to SCF-containing combinations of multiple cytokines. In long-term liquid suspension cultures, flt3L was less mitogenic than SCF but its effect on the maintenance of progenitors was superior that of SCF and of IL-3, IL-11, and G-CSF. The total number of clonogenic AA cells increased as much as four-fold during the first culture week and FACS analysis demonstrated expansion of the CD34+CD38+ progenitor cell subset. Despite this enhancement, survival of AA cells remained significantly poorer than that of normal cells, in which the primitive subset of CD34+CD38- cells was maintained up to 4 weeks when flt3L was used as a single factor. Both in normal and AA cultures, flt3L promoted differentiation of cells of the myeloid lineages. In cultures of bone marrow stroma, flt3L had almost no effect on growth and survival of AA progenitors, while in cultures of normal cells the number of colony-forming cells increased up to 10-fold. Although flt3L does not overcome the proliferative defect of AA precursors, we conclude that the ligand is capable of in vitro stimulation and expansion of the reduced progenitor cell pool in AA, when used in appropriate culture conditions. The in vitro effects of flt3L on AA cells differ in many aspects from those of the structurally related cytokine SCF, suggesting a benefit in use of a combination of these two early-acting growth factors.

Synergy of growth factors during mobilization of peripheral blood precursor cells with recombinant human Flt3-ligand and granulocyte colony-stimulating factor in rabbits.

The potential of recombinant human (rh)Flt3 ligand (FL), alone or in combination with other recombinant growth factors, to mobilize peripheral blood precursor cells (PBPCs) was examined in an animal model. Adult outbred New Zealand White rabbits received subcutaneous injections daily for 14 days in a standardized protocol; whole blood cell counts and colony-forming unit-granulocyte/macrophage (CFU-GM) colonies were measured 3 times weekly during the injection period and for an additional observation period of 14 days. Two animals in each group were treated as follows: 200 or 500 microg/kg FL, 10 microg/kg granulocyte colony-stimulating factor (G-CSF), 10 or 75 microg/kg stem cell factor (SCF), 10 microg/kg G-CSF + 500 microg/kg FL, 10 microg/kg G-CSF + 75 microg/kg SCF + 500 microg/kg FL. Both G-CSF and FL induced a sustained and dose-dependent increase in the leukocyte count to a maximum of 5-fold. They were additive in combination, leading to a tenfold increase in white blood cell counts. No consistent pattern was observed for platelet counts or red blood cells. No toxic side effects were seen. Both G-CSF and FL mobilized CFU-GM in a dose-dependent fashion to a 59-fold increase for G-CSF and 116-fold for FL. Maximum mobilization occurred on day 4 with G-CSF and on day 11 with FL. G-CSF + FL in combination acted synergistically, inducing a 503-fold increase of CFU-GM over baseline. The addition of SCF to this combination did not alter leukocyte counts or CFU-GM mobilization. Our results indicate that FL is a potent and safe agent for the mobilization of PB-PCs and is synergistic with G-CSF.

The membrane-bound isoform of stem cell factor synergizes with soluble flt3 ligand in supporting early hematopoietic cells in long-term cultures of normal and aplastic anemia bone marrow.

The hematopoietic growth factors stem cell factor (SCF) and flt3 ligand (flt3L) are produced within the hematopoietic microenvironment in a membrane-bound and soluble isoform. To elucidate the relevance of the two isoforms in the network of early-acting cytokines, we examined the interaction of membrane-bound SCF with the soluble forms of SCF and flt3L in long-term cultures of human bone marrow cells. Feeder layers of the murine SCF-deficient Steel stromal cell line transfected with human cDNA stably expressing SCF as a transmembrane molecule were used to support growth of mononuclear cells and CD34+ progenitors derived from normal human bone marrow or from hypoplastic marrow of patients with aplastic anemia (AA). The output of nonadherent progenitor cells representing colony-forming units (CFU) and high-proliferative potential colony-forming cells (HPP-CFC) was scored weekly in secondary methylcellulose cultures; the number of colonies derived from long-term culture-initiating cells (LTC-IC) was determined in nonadherent and adherent cells at 5 weeks. Membrane-bound SCF expressed in the stromal layer was more effective than soluble SCF and soluble flt3L in maintaining clonogenic progenitors. Furthermore, the transmembrane form of SCF effectively synergized with both exogenously supplied factors, although the effect of flt3L was superior to the effect of soluble SCF. In cultures of normal bone marrow cells, addition of flt3L enhanced the total number of CFU and HPP-CFC-type progenitors, primarily of the granulocyte/macrophage lineage, by six- to ninefold after 3 weeks and of LTC-IC-derived colonies by 13-fold after 5 weeks of culture. In cultures of AA cells, both the number and the survival rate of clonogenic precursors were severely impaired even in the presence of flt3L, which, however, yielded a two- to sixfold enhancement of CFU and HPP-CFC numbers at 1 to 2 weeks. In comparison with the hematopoietic function of human Dexter-type stroma cultures, murine feeders expressing high levels of membrane-associated human SCF were equivalent in supporting hematopoiesis during the initial 3 to 4 culture weeks when supplemented with flt3L. These results demonstrate that soluble flt3L interacts with membrane-bound SCF in supporting the long-term growth of bone marrow progenitor cells. The hypothesis that SCF and flt3L function synergistically during the very early stages of human hematopoiesis is thereby reinforced.

Umbilical cord blood from preterm human fetuses is rich in committed and primitive hematopoietic progenitors with high proliferative and self-renewal capacity.

Human umbilical cord blood (CB) has been recognized as a source of hematopoietic stem cells for transplantation. While hematopoietic properties of neonatal CB from full-term pregnancies have been well characterized, little is known about CB from early gestational ages. We analyzed the content and the growth properties of primitive and committed hematopoietic progenitors in preterm CB from second trimester (week 16-28; n = 17) and early third trimester (week 29-34; n = 17) in comparison with term CB (n = 18). The frequency of CD34+ and CD34+CD38- cells was significantly higher in preterm than in term CB (mean, 2.51% and 0.56% vs 0.88% and 0.13%;p < 0.002). The number of colony forming units (CFU) in preterm CB was about twofold higher (230 +/- 6 vs 133 +/- 14/ 10(5) mononuclear cells; p < 0.05) and correlated with the content of CD34+ progenitors (r = 0.73). Long-term culture initiating cells (LTC-IC) were enriched about 2.5-fold (6.7 +/- 2.9 vs 2.6 +/- 1.2/10(5) cells; p < 0.05). Progenitors from preterm CB could be expanded in stroma-free liquid cultures supplemented with hematopoietic growth factors as efficiently as progenitors from term neonates. In short-term cultures containing erythropoietin (Epo), interleukin (IL)-1, IL-3, and IL-6, or granulocyte- (G-) and granulocyte-macrophage colony-stimulating factor (GM-CSF) together with stem cell factor (SCF) or Flt3 ligand (FL), expansion of CFUs was six- to eightfold at week 1. In long-term cultures containing thrombopoietin (TPO) and FL, an approximately 1000-fold expansion of multilineage progenitors was observed at week 10. In summary, we show that preterm CB compared with term CB is richer in hematopoietic progenitors, and that precursors from preterm CB can be extensively expanded ex vivo. This may have implications for the development of transplantation and gene transfer strategies targeting circulating fetal stem cells.

Stable transduction with lentiviral vectors and amplification of immature hematopoietic progenitors from cord blood of preterm human fetuses.

Umbilical cord blood (CB) from the early gestational human fetus is recognized as a rich source of hematopoietic stem cells. To examine the value of fetal CB for gene therapy of inborn immunohematopoietic disorders, we tested the feasibility of genetic modification of CD34(+) cells from CB at weeks 24 to 34 of pregnancy, using lentiviral vector-mediated transfer of the green fluorescent protein (GFP) gene. The transduction rate of CD34(+) cells was 42 +/- 9%, resulting in GFP expression in 23 +/- 4% of colonies derived from colony-forming units (CFUs) and 11 +/- 1% from primitive long-term culture-initiating cells (LTC-ICs). Cell cycle analysis demonstrated transduction and GFP expression in cells in the G(0) phase, which contains immature hematopoietic progenitors. Transduced fetal CD34(+) cells could be expanded 1000-fold in long-term cultures supplemented with megakaryocyte growth and development factor along with Flt-3 ligand. At week 10, expression of GFP was observed in 40.5 +/- 11.7% of CFU-derived colonies. While prestimulation of CD34(+) cells with cytokines prior to transduction increased the efficiency of GFP transfer 2- to 3-fold, long-term maintenance of GFP-expressing CFUs occurred only in the absence of prestimulation. The GFP gene was found integrated into the genomic DNA of 35% of LTC-IC-derived colonies initiated at week 10, but GFP expression was not detectable, suggesting downregulation of transgene activity during the extended culture period. These results indicate that human fetal CB progenitors are amenable to genetic modification by lentiviral vectors and may serve as a target for gene therapy of hematopoietic disorders by prenatal autologous transplantation.

Allogeneic peripheral blood precursor cell transplants in rabbits.

This report summarizes a series of experiments undertaken to evaluate the role of mobilized peripheral blood precursor cells (PBPC) for transplantation across a major histocompatibility barrier. Adult outbred red Burgundy rabbits were used as donors, New Zealand white rabbits of the opposite sex as recipients. Conditioning consisted of single dose total body irradiation (TBI) of 10 Gy supported by a short course of cyclosporine to enhance engraftment. Human recombinant G-CSF at a dose of 10 micrograms/kg was used for mobilization of precursor cells. Three methods of PBPC transplants were tested initially in 5 animals each. PBPC were collected and infused at once on day 0; collected initially, cryopreserved for one month, infused on day 0 and followed by 3 additional fresh donations or collected and infused on 6 occasions between days 0 and + 11. 13 animals engrafted, 2 became complete, longterm chimeras. Survival was best in the group given repetitive infusions (39 days median, 12 days to > 180 days, range). 10 additional animals were transplanted as in the last group and the number of transplanted nucleated cells (10.5 x 10(8)/kg median, 7.3 - 15.7 x 10(8)/kg range) and colony forming units CFU-GM (42 x 10(4)/kg median, 12.3 - 176.8 x 10(4)/kg range), were compared with outcome. Median survival of the 10 animals was 29 days (12 - 55 days range; 1 autologous reconstitution). Survival did not correlate with total nucleated cells per kg (r = 0.10; p = 0.79), but there was a trend to prolong survival with higher numbers of CFU-GM per kg (r = 0.47; p = 0.19). These data show that allogeneic PBPCT can engraft across a major histocompatibility barrier, that the high number of CFU-GM per kg might be advantageous, but also that additional methods are warranted to reduce acute GvHD.

Transplantation of G-CSF mobilized allogeneic peripheral blood stem cells in rabbits.

Mobilized peripheral blood precursor cells (PBPC) are used with increasing frequency to restore autologous hematopoiesis following high-dose radio-chemotherapy. The success of this method has aroused interest in the use of mobilized PBPC for allogeneic transplants. This approach would eliminate the need for marrow aspiration and general anesthesia. In this project we tested the feasibility of allogeneic histoincompatible PBPC transplants in rabbits. Adult outbred Red Burgundy rabbits were used as donors, histoincompatible New Zealand White rabbits of the opposite sex as recipients. One individual donor was used for one individual recipient. Conditioning consisted of 10 Gy total body irradiation (TBI). Donor animals were pre-treated with recombinant human granulocyte colony-stimulating factor (rh G-CSF) given s.c. at 10 micrograms/kg daily. Three schedules of PBPC collection and reinfusion were tested in 3 groups of animals, each consisting of 5 donor recipient pairs: (A) PBPC were collected either on days -2, -1 and 0, and infused at once after TBI on day 0; (B) collected and infused on days 0, +2, +4, +7, +9, and +11; (C) collected on 3 consecutive days, cryopreserved for 1 month and infused on day 0 followed by 3 fresh donations on days +4, +8 and +11. The median amount of blood processed from donor animals was 470 ml (312-602) containing about 10 x 10(8) (5-71 x 10(8)) nucleated cells. Recipient animals received a median of 2.7 x 10(8) cells/kg equivalent to 9.6 x 10(4) colony-forming units granulocyte-macrophages (CFU-GM)/kg (data derived from Group C of the animals).(ABSTRACT TRUNCATED AT 250 WORDS)

Successful treatment of refractory acquired pure red cell aplasia (PRCA) by allogeneic bone marrow transplantation.

This case describes a 16-year-old woman treated successfully by a bone marrow transplant from her HLA-identical brother for refractory acquired pure red cell aplasia. Conditioning was as for severe aplastic anaemia with cyclophosphamide 4 x 50 mg/kg and antithymocyte globulin. Complete donor type engraftment at 3 months reversed to full autologous reconstitution at 2 years with normal haemopoiesis. The potential implications on pathogenesis of the disease as well as on treatment of autoimmune disorders by stem cell transplantation are discussed.

Preparation and characteristics of the structure of methoxyamine-modified f2 RNA.

Treatment of phage f2 RNA with [14-C]methoxyamine under non-denaturing conditions resulted in modification of exposed cytosines only. On methoxyamine treatment in the presence of 6 M-guanidine, all cytosines were modified. Under the conditions applied, no modification of adenine base in RNA chain occurred. The structure of modified f2 RNA preparations was studied by melting and sedimentation analysis. The ratio between the modification products (N-4-methoxycytosine and N-4-methoxy-6-methoxyamino-5,6-dihydrocytosine) was determined in RNA preparations modified under non-denaturing and denaturing conditions.

Activity of methoxyamine-modified f2 RNA in initiation and elongation steps of protein synthesis.

1. Messenger activity of phage f2 RNA modified with methoxyamine under non-denaturing conditions was studied in E. coli-free system. The incorporation of amino acids into phage polypeptides was decreased, and the synthesis of phage-specific proteins was diminished. The RNA replicase synthesis was more affected than synthesis of coat protein. The impaired messenger activity of the methoxyamine-modified f2 RNA was due to the blocking of elongation process by modified cytosines present in RNA chain. 2. Specificity of f2 RNA to stimulate ribosomal binding predominantly at the coat protein initiation site was not affected by methoxyamine-treatment, as demonstrated by unchanged binding of f[3H]Met-tRNA and [14C]alanyl-tRNA to ribosomes. 3. Unfolding of f2 RNA molecule on treatment with methoxyamine in the presence of guanidine-HCl resulted in a significant increase of RNA capacity to direct fMet-tRNA binding to ribosomes. Sucrose-density gradient profiles revealed the formation of polysome-like initiation complexes indicating that ribosomes were able to bind at many hitherto inaccessible initiation codons in RNA molecules. fMet-tRNA bound to ribosomes in the presence of unfolded RNA was found to be fully reactive with puromycin.

Clinical symptoms and signs useful in the early diagnosis of ankylosing spondylitis.

Seventy patients between the ages of 18 to 30 with early spondylitis (eAS), with bilateral grade II-III sacroiliitis without syndesmophytes were examined. The control group comprised 32 patients of the same age range with lumbar disc disease (LDD) confirmed by radiculography, without changes in the sacroiliac joints. In both groups the same clinical parameters were evaluated, calculating for each the specificity, sensitivity and Youden index. Statistical analysis was done using Student's t-test and/or the chi-square test. A complex of simple clinical features was isolated suggesting presence of eAS in young subjects with persistent low back pain but without a clear-cut radiological appearance of the sacroiliac joints. The complex included: a history of morning back stiffness, swelling of knee joints, thoracic pain, clinical evidence of limited chest expansion below 5 cm, swelling of joints of lower extremities, positive Mennell's sign, and in laboratory investigations presence of raised ESR and HLA B27-antigen.

Laboratory investigations of the effects of predator sex and size on prey selection by the Asian crab, Hemigrapsus sanguineus.

Laboratory studies have shown that the nonindigenous Asian shore crab, Hemigrapsus sanguineus, readily consumes three species of commercial bivalves: blue mussels, Mytilus edulis, soft-shell clams, Mya arenaria, and oysters, Crassostrea virginica. Although crabs can eat bivalves of a wide size range, they preferred the smaller prey (

[Coexistence of idiopathic spontaneous nocturnal enuresis and migraine in children]. / Wspólistnienie samoistnego mimowolnego maczenia nocnego i migreny u dzieci.

In a 7-year prospective follow-up of 104 children with enuresis in 32 cases (19 boys and 13 girls) coexistence of common migraine was found. Twenty-two children had various other seizure-like disorders, particularly tics, febrile convulsions, pavor nocturnus and fainting, and three had absence attacks. In 20 cases vasomotor disturbances and in 17 abnormal Schellong's test were found. The IQ was normal or high in all cases. Emotional disorders were observed in nearly half the cases. The water-salt test of Decourt was done in 9 cases and it was abnormal in 8 cases. At least two abnormal EEG records were obtained in 26 cases, and in 24 of them seizure activity was demonstrated in the EEG. In the period of follow-up disappearance or very marked improvement of enuresis occurred in all cases and migrainous attacks became less frequent and intense in 27 cases, while in 5 the severity of migraine increased. The author discusses the pathological mechanism of these disturbances calling attention to less good efficiency of the regulatory functions of the centrencephalic activating system and hypothalamus connected with biochemical and bioelectric immaturity.

[Evaluation of the results of treatment of SSPE (subacute sclerosing panencephalitis) with isoprinosine]. / Ocena wyników leczenia SSPE (subacute sclerosing panencephalitis) izoprynozyna.

The period of survival in the group of 36 boys and 18 girls with SSPE, as well as the condition of 13 living persons were examined. 30 children were treated with isoprinosine. A 3 years-long period of survival was significantly more frequent in the group of 18 children with long-term therapy by isoprinosine in comparison to 24 children without isoprinosine administration. The best results were observed in children with subacute course of the illness and many epileptic seizures. The 13 living persons are strongly damaged. One girl is decerebrated and 5 patients are completely helpless. The indications to isoprinosine therapy in SSPE are discussed.