Biomedical subjects
Publications and source records attributed to L Dénes.
In the therapeutically important range (100-200 micrograms/ml), suramin was found to increase the phagocytic activity of human monocytes (measured by the uptake of Saccharomyces cerevisiae and sensitized sheep red blood cells) in vitro. Suramin itself was a chemotactic signal for monocytes and increased the chemiluminescence of neutrophil granulocytes. Suramin seems to act via the ATP-binding P2 receptors of human phagocytes.
The authors review the experiences obtained during investigation of a patient with Klatskin tumor and whose clinical syndromes were developing as of virus hepatitis. In the first two weeks of the illness the clinical symptoms, the chemical laboratory findings and among the virus investigations the positive (experimental) Non-A Non-B hepatitis virus antigen suggested the existence of virus hepatitis. Later the laboratory investigations and the symptoms showed on obstructive icterus. The subsequent performed investigations as ultrasonography and PTC--showed the Klatskin tumor, which was proven by the operation performed and histology. The patient is free from the complaints more than 1 year after the operation, moreover recidivation or metastasis was not indicated by the investigations performed in the latest time.
Swiss male mice were immunosuppressed by cyclophosphamide, cisplatinum, vincristine and methotrexate. The ability of the thymopoietin (TP) fragments TP-3, TP-4 and TP-5 to restore antibody production and phagocytosis was studied. Impaired antibody production after vincristine treatment was partially or totally restored by TP-3, TP-4 or TP-5. Only TP-3 or TP-5 interfered with the antibody-production-damaging effect of cisplatinum. The same effect of methotrexate could not be influenced by any of the TP fragments. The phagocytic capacity of peritoneal macrophages was reduced by vincristine, methotrexate and cyclophosphamide treatment. In this respect, TP-3 protected the function of macrophages against vincristine and cyclophosphamide treatment. TP-4 was active in the case of damage caused by vincristine and methotrexate, and TP-5 interfered with the phagocytosis-inhibiting effect of methotrexate. Each TP fragment seems to have a specific target orientation within the immune system. This also means that the proper TP fragment should always be chosen for combination therapy with various types of cytotoxic drugs.
Suramin administration inhibits virus replication and produces impaired immunoregulation. Delayed type hypersensitivity (DTH)-reaction was inhibited by Suramin (200 mg/kg, i.p.) injection in guinea-pigs immunized with BCG vaccine. Suramin-inhibited DTH-reaction was restored to normal level after 4 days of treatment with thymopoietin 32-34 (TP 3) and TP5 (1 mg/kg, i.p.), TP3 greater than TP5. TP3 produced the strongest restoration when applied together with Suramin, but a single treatment with TP3 or TP5 oligopeptide inhibited the development of DTH-reaction. TP3 with Suramin treatment might be advantageous to eliminate defective side effects of Suramin on immune system and TP3 with indirect inducing action on IL-2, IFN-gamma production may be useful in therapy of AIDS patients.
The effects of thymic hormones are focused on the induction of T-cell subpopulations and restoration of the reactivity of an impaired immune system. TP3 and TP4 (corresponding to thymopoietin 32-34 and 32-35) exert a thymic hormone substitution effect. These peptides elicit dissimilar quantitative and qualitative effects. The aim of the present experiments was to investigate: (a) the effect of thymopoietin fragments in mice with unbalanced immune systems caused by experimental manipulation; and (b) the ratio of target cells after treatment. The distribution of Thy1, Lyt1, Lyt2 positivity was determined in a direct complement mediated cytotoxicity test. Autoantibody production was measured by Coombs' test. A count of Lewis Lung Tumour (LLT) metastases was made after two weeks of inoculation. Groups of mice were thymectomized and/or injected with cyclophosphamide (CY) (240 mg/kg) 96 h before tumour cell inoculation. The number of LLT metastases was decreased by treatment with peptides (TP3 = 72, TP4 = 97, TP5[thymopoietin 32-36] = 83.1 in %) and immunosuppression produced by CY was partly restored. After thymectomy, however, only TP3 treatment caused a decreasing effect (97.4%) on CY immunotoxicity independently of thymectomy. Inhibition of autoantibody production was detected with TP3 (5-6 weeks earlier than in mice treated with TP5). The ratio of Thy1+ and Lyt2+ cells was increased by treatment with TP3 and TP4, but the ratio of Lyt1+ cells was decreased by application of TP5. After TP3 treatment of nude mice the Lyt1+/Lyt2+ ratio increased both in bone marrow and spleen. No effect of TP4 was observed on Lyt 1+ cells, but the number of Lyt2+ increased in bone marrow.(ABSTRACT TRUNCATED AT 250 WORDS)
The authors reported the results of a clinical, radiological and immunological study of 147 primary pulmonary cancer cases who were immunostimulated with BCG vaccine over a period of three years between 01.01.76 and 31.12.78. Compared with the same number and stage of cancerous patients treated with the same cytostatic drugs and/or surgically without BCG immunostimulation, the survival rate of the immunostimulated group was higher than that of the control group. The radiological picture did not change during the study time in 45% of the patients, regression was observed in 34%, and progression in 21% in the Stage I vaccinated group, while in the control Stage I group regression was only noticed in 21%, and progression was observed in 50%. In the Stage II vaccinated group regression was noted in 48%, in the control group in 23%. No favourable changes were noted in Stage III groups, neither in the vaccinated nor in the nonvaccinated cases. The more favourable prognosis of the immunostimulated group was reflected in the results of the skin tests and in the cellular and humoral immunological responses too. The modification of the BCG immunostimulated pulmonary cancer patients gives a statistically significant prolongation of survival time and a beneficial improvement of life quality and expectation.
The immunostimulatory action of oligopeptides RGH-0205 (Arg-Lys-Asp), RGH-0206 (Arg-Lys-Asp-Val) and TP-5 (Arg-Lys-Asp-Val-Try) was measured using the B10LP to C57BL skin graft system and the determination of splenic T cell ratio. While thymectomy increased the period between skin grafting and rejection, each of the oligopeptides increased the number of splenic T cells and in some extent restored the rejection capacity of thymectomised C57Bl mice, presumably by restoration of thymic hormone function.
Seventeen peptides, related to thymopoietin pentapeptide, L-arginyl-L-lysyl-L-aspartyl-L-valyl-L-tyrosine (thymopentin) were synthesized by the stepwise strategy in solution. Of these, L-arginyl-L-lysyl-L-aspartic acid and L-arginyl-L-lysyl-L-aspartyl-L-valine, shortened from the C-terminus of the pentapeptide, exhibit significant immuno-stimulating potencies, exceeding those of thymopentin, both in vitro and in vivo immunological tests. Studies on the structure-activity relationships suggest that the potencial active site of thymopoietins is very sensitive to the N- and C-terminal elongations of the peptide chain. For thymic hormones, an active site carrying cumulative chemical signals is proposed instead of well-defined active centers.
Immunological disorders may cause altered motility or attachment of leukocytes. Active adherence of buffy cost cells derived from normal subjects and with autoimmune diseases patients and complement dependency of this process was studied on glass surfaces. The adherence of leukocytes of both normal persons and of SLE and RA patients was decreased in the presence of normal human serum compared to serum-free medium. The effects of native and heat inactivated human sera on leukocytes of SLE and RA patients were compared. Adherence of SLE leukocytes was higher, whereas that of RA leukocytes was lower in unheated serum compared to heat inactivated human serum. Supernatants of leukocytes of SLE, RA patients and control subjects were harvested after incubation in serum-free medium. The C3 levels of supernatants were determined by rocket electrophoresis. Surface attached C3 was detected with immunofluorescence mainly on SLE leukocytes. The cellular effects of supernatants on control leukocytes, were consistent with the changes observed with leukocytes derived from SLE, RA or control patients.
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