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Biomedical subjects

E M Lemmel

Publications and source records attributed to E M Lemmel.

At least 37 records · Page 2Linked to original sources

[Immunomodulating therapy in chronic polyarthritis with thymopentin. A multicenter placebo-controlled study of 119 patients].

In a multicenter, placebo-controlled and randomized double-blind trial 119 patients with rheumatoid arthritis were treated with thymopentin, an immunoregulating drug. The data of 107 patients were complete enough to be evaluated: 51 were given intravenous injections over ten minutes of 50 mg thymopentin three times weekly, 56 were similarly treated with a placebo solution. Significant improvement of five among nine clinical criteria were obtained with thymopentin after the third week of treatment. The response rate (improvement of a clinical parameter by at least 40%) was significantly greater for all clinical parameters in the thymopentin group. Regression to a functionally more favourable class (Steinbrocker's classification) occurred in seven thymopentin-treated, but in none of the placebo-treated patients. The improvement gradually subsided over four weeks after the end of treatment. There were no changes during the trial with respect to immunological, biochemical or haematological findings. Except for one systemic allergic reaction there were no side effects.

Adjuvants, Immunologic↗

Results of a multicenter placebo-controlled double-blind randomized phase III clinical study of treatment of rheumatoid arthritis with recombinant interferon-gamma.

In a multicenter placebo-controlled double-blind randomized clinical study, 91 patients with rheumatoid arthritis were given 28 days' treatment with recombinant interferon-gamma (50 micrograms daily for 20 days, then 50 micrograms each second day up to day 28, given by subcutaneous injection). The aim of the study was to provide a methodologically clear demonstration of the efficacy of treatment with interferon-gamma, using criteria that could be handled by statistical tests. Evaluatable documentation was available for 79 patients, of whom 40 were treated with the active compound. The principal criterion for the statistical evaluation of the therapeutic success was improvement of the Ritchie "joint pain index" or Lansbury "joint pain index" by at least 30% within 28 days. The chi-square test showed superiority of the interferon arm over the placebo arm with an error probability of alpha less than 1%. In addition, efficacy of interferon-gamma was demonstrated in respect of practically all parameters investigated. The frequency of side-effects, including febrile reactions, was the same for the active compound and the placebo. During interferon treatment the daily maximum body temperature was raised by 0.3 degrees C on average, but was below 37.2 degrees C at all times.

Adolescent↗

Azimexone and cysteine hydrazide in the treatment of allergic encephalomyelitis.

In the course of allergic encephalomyelitis (EAE) in chickens, azimexone suppressed the production of the specific IgM immunoglobulins. Moreover, it decreased the level of haptoglobin and sialic acid but stimulated the activity of antitrypsin. It was also observed to reduce the production of the plasmatic cells in the spleen. L-cysteine hydrazide hydrochloride decreased the level of sialic acid in EAE; intensified the activity of trypsin inhibitor and exerted no effect upon the level of antimyelin antibodies.

Animals↗

Results of a phase-II clinical trial on treatment of rheumatoid arthritis with recombinant interferon-gamma.

In an open, non-randomized clinical trial conducted at multiple centres, 49 patients with rheumatoid arthritis were treated with recombinant interferon-gamma for 20 days. The study was carried out in two sub-studies. In the first, the total daily dose of interferon-gamma was 50 micrograms; in the second, 100 micrograms. Of the 49 cases, 40 were evaluable for statistical analysis; 24 of these patients (60%) responded to therapy, according to the criteria of a successful outcome laid down in the study protocol, and were classified as responders. In responders, the clinical parameters investigated improved with both dosages. The lower dosage differed from the higher one in having a markedly lower incidence of side-effects. The results lead to the conclusion that a randomized double-blind phase-III clinical trial should be performed.

Adult↗

The influence of thymus hormones on the NK cells activity.

The influence of thymus hormone preparations on NK cell activity was studied. The following preparations were used: crude extract from calf thymus (TFX), its fraction V (TFX V) and synthetic pentapeptide (TP-5) fragment of native hemopoietin. It was shown that all preparations under study activate NK cells in vitro. The weakest effect was observed in the case of TFX, while both TFX V and TP-5 showed equally good stimulatory properties. The obtained results are discussed. The weak effect of the crude TFX is probably caused by the fact that it contains only 15% of fraction V which is responsible for affinity to the immune system.

Cell Line↗

Cyclophosphamide in allergic encephalomyelitis in chickens.

The studies concerned the effect of cyclophosphamide on immunological and biochemical indices of MBP-induced encephalomyelitis. Unlike isoprinosine, cyclophosphamide was observed to exert irregular effect. Contrary to the expected, the results obtained in some experimental systems show increased level of the parameters tested-IgG, antitrypsin and sialic acid. A suggestion has been put forward that the reason of the above phenomenon may be attributed not only to the type of drug applied but also to different course of treatment with regard to various affinity of the drug (different doses) to functionally different lymphocytes (suppressor, helper).

Animals↗

Modulation of immunological reactivity in the course of allergic encephalomyelitis by isoprinosine.

It was observed that in the course of allergic encephalomyelitis (EAE) in chickens. Isoprinosine reduced the production of the specific IgA and IgM antibodies against encephalic antigen. Its influence on IgG production was slight. It was also found that isoprinosine reduced the antitrypsine activity in EAE. Its effect upon the level of antibodies and biochemical indices of inflammation was particularly pronounced on days 28-35 after immunization, i.e. at the time of the most intensive microscopic inflammatory changes in the brain. Histological analysis revealed an inhibition of plasmatic cells reproduction in the spleens of chickens receiving isoprinosine. No effect of the drug on the GvH reaction in chickens was found.

Animals↗

Measurement of the respiratory burst in human monocytes and polymorphonuclear leukocytes by nitro blue tetrazolium reduction and chemiluminescence.

We compared measurements of chemiluminescence (CL) assessing the rate of production of oxygen intermediates at a given instance, and of nitro blue tetrazolium (NBT) reduction detecting total superoxide produced during the assay period, for the assessment of the respiratory burst of both human monocytes (M phi) and polymorphonuclear leukocytes (PMN). In the CL experiments, opsonized and non-opsonized zymosan was used to stimulate peripheral blood M phi and PMN. Opsonized zymosan yielded an earlier and 2-fold higher peak response than non-opsonized zymosan. The stimulatory action of zymosan in CL varied with the time of incubation and depended on the concentration of cells and zymosan. No light generation was observed in the absence of viable cells. In contrast to NBT reduction, incubation of PMN with dextran sulfate did not result in increased light generation but rather in a quenching of the response in CL. Opsonized zymosan also yielded a higher level of NBT reduction than non-opsonized zymosan. Comparing NBT reduction with CL in 21 healthy individuals, with 2 X 10(5) M phi and 2.5 X 10(5) PMN for NBT and 5 X 10(5) PMN for CL tests, we found that NBT brings about spontaneous oxidative metabolism, possibly reflecting the intracellular compartment, the chemiluminescent response of resting cells being only marginal. The data suggest higher sensitivity of the CL method. These results provide useful comparative data for 2 established methods used to document the respiratory burst in phagocytic cells.

Adolescent↗

Studies on the mechanism of PMN activation III. by lymphokines.

The influence of a guinea pig lymphokine preparation on the oxidative metabolism of human and guinea pig granulocytes of various sources was investigated. A dose-dependent increase of the oxidative burst following lymphokine challenge was observed. It occurred in unstimulated guinea pig peripheral polymorphonuclear leukocytes (PMN) and in prestimulated PMN obtained from the peritoneal cavity after glycogen injection as well. The lymphokine effect on the oxidative metabolism is not species-restricted because the guinea pig lymphokine preparation elicits an oxidative burst in human PMN, too. The increase caused by lymphokines is nearly of the same order of magnitude as that obtained with zymosan.

Animals↗

Reduction of the immunosuppressive action of chemotherapeutics in patients with mammary carcinoma by Azimexon.

Patients treated by aggressive cytostatic treatment exhibit marked deficiencies in cell-mediated immunity. Our investigations were performed in order to find out whether these immunosuppressive effects could be diminished by supportive treatment with the new synthetic immunomodulating compound BM 12.531, INN: AZIMEXONE. After inducing remission in ten patients with metastasizing breast cancer by a combination chemotherapy given for about one year, leucocytes, T- and B-lymphocytes and reactivity of peripheral lymphocytes to different mitogens were determined at weekly intervals before (8 X), during (8 X while on 100 mg i.v. weekly, then 4 X while on 400 mg i.v. weekly) and after (4 X) treatment with AZIMEXONE. Chemotherapy-induced immunosuppression could be markedly diminished during the administration of AZIMEXONE. A significant increase in the peripheral leucocyte count and mitogen-induced lymphocyte transformation could be achieved without any marked influence on the percentages of T- and B-cells. No severe side-effects of AZIMEXONE were observed.

Aziridines↗

Control of the production of oxygen intermediates of human polymorphonuclear leukocytes and monocytes by beta-adrenergic receptors.

The control by beta-adrenergic receptors of the production of oxygen radicals by zymosan-stimulated human polymorphonuclear leukocytes (PMN) and monocytes (M phi) was studied in vitro by means of chemiluminescence. In addition we asked whether PMN and M phi exhibit differential sensitivity to beta-adrenergic stimulation. For beta-adrenergic stimulation we applied fenoterol ranging from 10(-5) to 10(-9) M x 2.7. We found a dose-dependent suppression of the production of oxygen radicals, the ID50 being approximately 10(-6) M both for PMN and M phi. By assessment of lactic dehydrogenase release a cytotoxic effect of the drug could be ruled out. When incubated together with the beta-adrenergic antagonist propranolol at 10(-6) and 10(-7) M the suppression effect of fenoterol could be reversed in dose-dependency. Preincubation with fenoterol revealed that the inhibitory action on M phi persisted, in contrast, no such suppression could be verified with PMN. Our findings indicate the control of the production of oxygen intermediates of human PMN and M phi by beta-adrenergic stimulation. Furthermore, selective functional modulation of resting PMN and M phi by beta-adrenoceptors is suggested. These effects may be of importance in vivo, in particular since fenoterol was applied in pharmacological doses.

Fenoterol↗

[The Crithidia luciliae immunofluorescence test for detection of antibodies to double-stranded DNA (author's transl)].

For measurement of antibodies of double-stranded DNA (ds DNA) the Crithidia luciliae immunofluorescence test (C1-IFT) was compared with the Farr precipitation technique in diagnosis and management of systemic lupus erythematosus (SLE). The C1-IFT proved to be less sensitive in SLE patients without clinical disease activity, but the sensitivity of the test in those with active disease was comparable to that of the Farr test. In 76.9% of the patients' sera identical test results were obtained by both assays. In some sera antibodies were detected only by the C1-IFT. Positive test results in patients with diseases other than SLE were found more often with the Farr test. Thus, The C1-IFT seemed to be more specific for diagnosis of SLE. Measurement of titers using the C1-IFT provides a simple method to survey SL E disease activity. It allows to analyze the immunoglobulin classes of the reacting antibodies and their complement fixation ability in vitro. All three major immunoglobulin classes (IgG, IgM, IgA) were found to be present in the sera with high antibody titers, complement fixation in the C1-IFT could predominantly be detected is sera with high antibody titers.

Antibodies, Antinuclear↗

Studies on the mechanism of PMN activation. II. By triggering the alternative pathway of complement activation.

By means of cobra venom factor (CVF) it is demonstrated that the stimulation of hexosemonophosphate shunt (HMPS) of human polymorphonuclear leukocytes (PMN) by zymosan (Z) and dextran sulfate (DS) is caused by at least two models of activation: (a) via activation caused by phagocytosis, (b) via activated alternative pathway of complement activation (APC). Active factors of APC presented with phagocytizable objects strongly enhance activation of PMN. The effect of APC can be observed in serum-containing as well as in serum-free cultures. It can be demonstrated that in serum-free cultures the factors of APC participating in the activation of PMN are supplied by monocytes. By use of synthetic hexapeptide (HP) representing the COOH-terminal sequence of human C3 further evidence is provided that factors of APC are able to activate the PMN.

Complement Activation↗

Increased respiratory burst activity of monocytes and polymorphonuclear leukocytes in psoriasis.

We studied the respiratory burst activity of peripheral blood monocytes and polymorphonuclear leukocytes (PMN) in eleven patients with psoriasis and eleven healthy controls, using zymosan particles to activate the phagocytes in vitro. The activation of the phagocytes was measured in a luminol-enhanced chiluminescence (CL) assay. We found a significantly higher respiratory burst activity of both monocytes and PMN in patients with psoriasis compared with the control subjects. The percentages of monocytes in psoriatics did not differ from those of the controls. The higher amount of zymosan-induced CL activity generated in the patient group was unrelated to the age of the individual. Our data indicate increased metabolic reactivity of both monocytes and PMN in psoriasis.

Adult↗