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[Use of immunomocorrection in the combined treatment of laryngeal papillomatosis in children].

Original immunological studies allowed the authors to design a combined treatment of laryngeal papillomatosis (LP) with administration of immunomodulators and cytostatics. Surgery was performed on demand. Thymic hormone preparation (T-activin, thymalin, thymogen) and prospidin served as immunomodulators and cytostatic, respectively. To create lymphotropism, prospidin was delivered by means of electrophoresis following subcutaneous introduction of 8--16 U lidase. Sensitivity of patients to thymalin was tested in vitro by thymalin-induced changes in the number of CD2--DR+ lymphocytes. Adjuvant modalities were age-adjusted dibasol as inductor of interferon genesis and adaptogens (eleutherococcal fluid extract, B and C vitamins). Such treatment was given to 39 children. Remission duration increased 1.6--2.6-fold, 6 of 7 children with primary LP achieved persistent remission. Positive changes in immunological indices occurred in 84% of children. The above treatment outcomes support the efficacy of the method in childhood LP.

Adjuvants, Immunologic↗

Mammalian DNA ligases. Serological evidence for two separate enzymes.

Mammalian cells contain two DNA ligase activities with different chromatographic properties, referred to as DNA ligase I and II. The major ligase activity present in calf thymus cell extracts, DNA ligase I, has been purified 1000-fold. After repeated injections of this enzyme with complete Freund's adjuvant into a rabbit, antibodies were induced that inhibit DNA ligase I from calf, human, mouse, and rabbit tissues. This antiserum did not affect DNA ligase II from the same sources to a detectable extent, even at a concentration 10-fold higher than that required for 98% inhibition of DNA ligase I. These data strongly indicate that the two mammalian DNA ligase activities are due to two separate enzymes, and not to two forms of the same enzyme. Both enzymes are present in the nuclear fraction, but are also found in the cytoplasmic fraction. Rapidly dividing cells (mouse ascites tumor cells and calf thymus) contain higher amounts of DNA ligase I than other cells (calf liver and spleen, human placenta, and rabbit spleen), while no such correlation was observed for DNA ligase II.

Animals↗

New preparative schedule and further characterization of a thymocyte specific growth factor from calf thymus.

Purification of a thymocyte specific growth factor is described. A formic acid extract of calf thymus was acetone precipitated, extracted with acidic methanol and precipitated with ether. With an assay based on the stimulation of DNA synthesis in thymocyte cultures the crude extract was purified by several steps of gel filtration and ion exchange chromatography. The stimulating activity had an apparent Mr of 1,600 and a pI of 5.6-5.9 and was devoid of reactive amino groups. It behaved amphoteric and was sensitive to pronase. We propose that the activity resides in an N-terminal-blocked peptide without biochemical relationship to defined thymic differentiation hormones or established growth factors.

Animals↗

Thymostimulin therapy in patients with measles meningoencephalitis.

Four children with measles meningoencephalitis were treated with thymostimulin, a calf thymic extract. All patients were comatose when therapy was started. In all but one a good and sometimes rapid clinical improvement was observed. In the responsive patients no neurological or EEG sequellae were noted over a follow-up period of 1-4 years. The depression of cell-mediated immunity, present in some patients before treatment, normalised at the end of therapy.

Child↗

Expression and modulation of the Lewis x antigen (CD15) on the T cell line Molt-4.

The T cell lines Molt-4 and H9 exhibited a characteristic distribution of the cell adhesion molecule Lewis x (CD15, lacto-N-fucopentanose III) showing an unusually broad peak by flow cytometry ranging from cells without CD15 to cells with high expression. The cytokines IL-1, IL-2, IFN-beta, IFN-gamma, and TNF-alpha, known to activate T cells, did not affect CD15 expression. However, phorbol myristate acetate and the thymic peptide extract Thymex-L were able to enhance both the number of CD15-positive cells and the median fluorescence. The effects of both inducers were dose- and time-dependent. An additive or synergistic effect was not seen. These data suggest that phorbol esters and distinct thymic peptides can modulate the expression of the cell surface antigen CD15.

Adjuvants, Immunologic↗

[Immunostimulation in heart surgery: thymostimulin. Preliminary data].

The immunodepressive effect of surgical procedures is well known. Immunotherapy with thymic hormones has used a long time to prevent surgical immunitary damage. In cardiac surgery, we can observe a hard immunitary depression caused by the cardiopulmonary bypass (CBP). In this paper we evaluate the response to immunotherapy, with an extractive thymic hormone: thymostimulin at the dosage of 1 mg/kg/day; 20 patients of a group of 40 underwent CBP. Immunological monitoring was obtained with the "multitest CMI", a disposable skin test to evaluate changes of lymphocytes, especially T cells. Results shows a significant increase of response in patients treated with thymostimulin versus control. A larger sample and a deeper immunitary assessment will be provided in the future.

Adjuvants, Immunologic↗

In vitro effect of TP-1 (a calf thymic extract) on suppressor T-cell function of patients with autoimmune chronic active hepatitis.

Concanavalin A-activated T-lymphocyte suppression of IgG production was found to be significantly impaired in patients with untreated active autoimmune chronic hepatitis when compared to normals or patients with inactive disease. When the dose-response effect of TP-1, a calf thymic extract, on in vitro suppressor cell activity was assessed, lymphocytes from six out of eight patients with previously reduced suppressor cell function showed a significant improvement, while over a similar range the suppressor cell activity of most normal controls declined. These results support the possibility that defective immunoregulation in patients with autoimmune chronic active hepatitis may be related to a deficiency in thymic hormone levels.

Adjuvants, Immunologic↗

Thymosin therapy in the DiGeorge syndrome.

Reconstruction of the T-cell immune defect in patients with the DiGeorge syndrome has been accomplished in the past by fetal thymus transplantation. Because of the risk of fatal graft-versus-host reaction with fetal thymus transplantation in patients with abnormal T-cell immunity, we have examined the effects of a thymus tissue extract, thymosin fraction 5, on the in vitro and in vivo immune function in children with the DiGeorge syndrome. T-cell numbers were increased with thymosin F5 in vitro in three of five patients. T-cell number and function was improved in three of four patients treated with thymosin F5 in vivo. Spontaneous improvement in the immune function of these patients cannot be excluded. These results suggest, however, that further trials with thymosin F5 therapy may be indicated in patients with the DiGeorge syndrome.

DiGeorge Syndrome↗

T-dependent immunity in aged humans. I. Evaluation of T-cell subpopulations before and after short term administration of a thymic extract.

T lymphocytes, T lymphocyte subpopulations and delayed hypersensitivity reactions to recall antigens were studied in 20 aged subjects clinically unaffected by disorders of the immune system. T-cells evaluated by the sheep rosette test and absolute T-cell number were within normal range. T-cell subsets were studied by the high affinity rosetting test and by the sheep rosette test after pre-incubation with theophylline; such methods have been shown by others to discriminate between T-cells with helper or suppressor activity. We did not observe an imbalance of such subpopulations. Skin reactivity to recall antigens (Candida and SK-SD) was depressed in several cases. Since a decline in serum levels of thymic hormones has been reported in the ageing and it is suggested that this could account for the T-dependent immunity defect, we treated these patients with a bovine thymic extract (thymostimulin, TP-1) 1 mg/kg/day for three consecutive days. Immunological tests were performed again after this therapy but no modifications were observed. We may conclude that the aged subjects studied in this paper present normal relative and absolute number of T-cells and T subpopulations, whereas the function of T-cells, as assessed by skin reactivity to recall antigens is often depressed. Short term therapy with TP-1 at the above mentioned dosage was ineffective in modifying the parameters analysed.

Aged↗

Morphometric analysis of peritumoral lymph nodes in patients operated on for uterine cancer, locally treated with a thymic extract.

By means of a morphometric analysis, the authors have evaluated the structure and dimensions of the lymph node functional areas (cortical, medullary, paracortical, histiocytosis of the sinuses, germinal centres) in regional nodes of women with carcinoma of the uterus in the 1st and 2nd stages. Twenty patients were treated 8 days before surgery with a dose of 1.5 mg kg-1 body weight of thymic hormone directly into the uterine portio. Ten patients, on the other hand, were injected with physiological saline solution. The quantitative and qualitative results show that in peritumoral lymph nodes of women treated with thymostimolin there is a marked increase, statistically significant (P less than 0.001), of the paracortical zone and of the number of germinal centres.

Female↗

Enhancement of phytohemagglutinin-induced lymphoproliferative response by indomethacin, Thymex L or their combination in lung cancer patients.

Several studies showed that thymic factors and prostaglandin synthesis inhibitors enhance in vitro lymphoproliferative response (LPR) to mitogens in cancer patients. In this study we investigated whether indomethacin and thymic extract (Thymex L), applied in combination, may in a synergistic pattern influence phytohemagglutinin-induced LPR in lung cancer patients. The results demonstrate that the use of the investigated agents enhances LPR to a similar level in hyporeactive patients before, as well as after, therapy. However, this drug combination exerts an additive effect on LPR, but only in patients who underwent cytoreductive radiation therapy, indicating the potential usefulness of this drug combination as an adjuvant treatment of these patients.

Adjuvants, Immunologic↗

Leukaemia-associated antigen in serum of patients with acute lymphoblastic leukaemia.

A antigen (HThy-L) previously found in extracts of human thymocytes and leukalphaemic cells was detected in sera from four patients with E-rosette-positive untreated acute lymphoblastic leukalphaemia (A.L.L.) and one patient with previously treated acute myelogenous leukaemia (A.M.L.) The disappearance HYth-L angignaplhaemia with treatment was coindent with a decrease in the number of leukaemic blast cells in the peripheral blood. HThy-L antigen was not detected in the sera of the remaining twenty-one patients with E-rosette-negative A.L.L. and seven patients with A.M.L..

Adolescent↗

Heterogeneity of immunological patterns in Langerhan's histiocytosis and response to crude calf thymic extract in 11 patients.

Response to treatment with daily intramuscularly administered crude calf thymic extract (Suppressin) in 11 patients with Langerhan's histiocytosis (L.H.) is reported. In ten patients, T-lymphocytic subsets were studied before starting immunotherapy: OKT3 positive and OKT4 positive cells were reduced in four patients; OKT8 positive cells were reduced in two patients; three patients were normal. After immunotherapy, one patient entered complete remission, four patients had stationary disease, and six had marked clinical progression. Subsequently eight patients underwent conventional chemotherapy, and only three entered complete remission. This study has demonstrated the heterogeneity of immunological patterns in L.H. and justifies the necessity for investigations on the immunoregulatory mechanism of L.H.

Child↗

Serial immunologic and histopathologic studies in the treatment of necrotizing fasciitis with combined immunodeficiency by a bovine thymic extract (thymostimulin).

A 25-day-old Chinese female baby developed necrotizing fasciitis (NF) with indurated erythematous patches with superficial necrosis over two thirds of the back. Skin cultures of the lesions yielded Streptococcus pyogenes, enterococcus, Pseudomonas aeruginosa, and Candida species. The patient had lymphopenia with low T cells and T cell subsets. The lymphoproliferative response to mitogen and macrophage migration (MIF) production were also poor. Her lymphocytes were unable to produce IgG in vitro. Also, IgG bearing cells were not demonstrable. The initial lymph node biopsy demonstrated an absence of follicular formation and depletion of lymphocytes in both thymic-dependent and thymic-independent areas. Five weeks after bovine thymic extract (Thymostimulin) treatment, a second lymph node biopsy demonstrated germinal centers containing IgG bearing cells. Three weeks later, a third lymph node biopsy showed germinal centers with cuffs of lymphocytes. Differentiation of the cortex and medulla of the node was demonstrated. IgG was also detectable in an in vitro Ig synthesis study. The total T cells, T cell subsets, lymphoproliferative response MIF production also increased gradually after Thymostimulin treatment. This investigation demonstrated the therapeutic effectiveness of Thymostimulin in NF with underlying combined immuno-deficiency, both serious and frequently fetal diseases, by the histologic and immunologic reconstitution of T and B cell function.

Adjuvants, Immunologic↗

Ivermectin, levamisole and thymic extract for chemotherapy and immunostimulation of visceral leishmaniasis in hamsters and mice.

The anti-leishmanial activity of ivermectin, pentostam or combination of pentostam with either levamisole or thymic extract was tested against Leishmania donovani infection in hamsters and mice. In vitro peritoneal macrophage-parasite interaction, the effect of splenic cells on the interaction of macrophages and parasites, spleen weight, parasite burden in spleen tissue as well as the antibody titers using micro-ELISA were used as parameters for evaluating the efficacy of these chemotherapeutic regimens. Treatment with ivermectin and immunoenhancement with pentostam combined with levamisole gave best results in both animal models. Furthermore, regimens used in this work were all active in reducing phagocytosis of promastigotes by macrophages in vitro.

Adjuvants, Immunologic↗

[Evaluation of the effectiveness of thymomodulin in children with recurrent respiratory infections].

Numerous trials of prophylaxis of recurrent respiratory infections in children have been performed, even though the only controlled trials providing incontrovertible results were the ones carried out with levamisole and thymostimulin through intramuscular administration. We have experimented a calf-thymic extract administered by oral route (thymomodulin). During the summer we enrolled 40 children aged between 3.5, and 9 years who had suffered from RRI during the previous winter. The patients were randomly divided in two groups and respectively treated with thymomodulin or with placebo; 21 children were given the thymic extract and 19 the placebo. The trial was carried out according to a double-blind schedule for a period of four months, from the beginning of October '84. At the end of the trial we assessed the catharral bouts observed during the research period by the family doctors and the parents evaluation on the clinical state. The difference between the two groups is statistically highly significant both with reference to the reduction of the total number of catharral bouts and to the general clinical state according to the parents opinion. The research clearly demonstrates the protective effect of the thymomodulin, probably due to the "restorative" effect on some immunological functions, temporarily compromised during the infection bouts.

Child↗

Effectiveness of thymostimulin and study of lymphocyte-dependent antibacterial activity in children with recurrent respiratory infections.

Recurrent respiratory infections (RRI) consist of more relapsing acute respiratory infections than the ones expected for the age [> 6 acute respiratory tract infections (RTI) per year if age is > 3 years, and > 8 acute RTI per year if age is < 3 years]. Concerning the pathogenesis of RRI, several investigations report the important role of environmental factors, early socialization and immunological dysfunctions, such as lymphocyte subpopulations alterations, IgG subclass deficiency and phagocytosis and/or opsonization deficit during acute infections. In this framework, we have studied the lymphocyte-dependent antibacterial activity (ABA) among 121 children affected by RRI. Results show a statistically significant alteration of this function in 38 children (31.4%): 19 of them exhibited an absent ABA (group 1), while in the others same function was reduced (group 2). A bovine thymic extract, thymostimulin, was administered to both groups by intramuscular injections (1 mg/kg) for a 3 month cycle. At the end of therapy we observed a statistical significant rise of ABA only in group 1 and among children aged > 3 years. Among the same patients, 33 children (86.8%) improved in terms of reduction of clinical score and better results were seen among children aged > 3 years. These data emphasize the beneficial role of thymostimulin in RRI-affected children, suggesting a transient immaturity of the immune system as one of the possible pathogenetic factor.

Adjuvants, Immunologic↗

Treatment of hepatitis B virus-associated membranous nephropathy with adenine arabinoside and thymic extract.

Previously we found that corticosteroid treatment in the hepatitis B virus (HBV)-associated membranous nephropathy (HBVMN) was not associated with a favorable outcome. To distinguish the differences of the HBV DNA in macrophage, T and B cells among HBVMN patients with or without corticosteroid treatment, serial studies at different time points were investigated. HBV DNA appeared as an "episomal" molecule as with 3.2 kb in macrophage, T and B cells. This molecule disappeared after 12 months among HBVMN patients without corticosteroid treatment. HBV DNA, by contrast, appeared as episomal form even three years later in T cells, with frequent proteinuria among HBVMN patients with corticosteroid treatment. This finding indicates that the use of corticosteroids leads to a potential risk of enhancing HBV viral replication in T cells. We studied 24 HBVMN patients who had previously received corticosteroid treatment and had persistent proteinuria, who were administered combination therapy with adenine arabinoside for two weeks and thymic extract (Thymostimulin) for six months to decrease urine protein loss and obtain seroconversion. These 24 patients had heavy (22 of 24, 91.6%) or mild (2 of 24, 8.4%) proteinuria prior to adenine arabinoside and thymostimulin treatment. All 24 patients demonstrated HBV DNA in mononuclear cells and simultaneously exhibited sera positive with HBsAg and HBeAg. In contrast, after treatment only one case (4.2%) had heavy and two cases (8.4%) mild proteinuria; HBV DNA was demonstrated in macrophage (4 of 24, 16.7%), T cells (9 of 24, 37.5%), and B cells (6 of 24, 25%) as well as serum (24 of 24, 100%) prior to treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗