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Biomedical subjects

G Fierlbeck

Publications and source records attributed to G Fierlbeck.

At least 55 records · Page 3Linked to original sources
PubMed1994

Chemotactic activity of substances derived from antibody-loaded tumor cells on granulocytes.

Chemotactic activity of granulocytes attracted by tumor cells loaded either with anti-ganglioside monoclonal antibodies (mAb) or with antibody-glucose oxidase conjugates (mAb-GO) was investigated. The melanoma cell line SK-Mel-28 which expresses the ganglioside GD3 at high density as well as the neuroectodermal cell line SK-N-LO which expresses GD2 were used for the experiments. In the presence of 50% human AB-serum, antibody-loaded tumor cells induced chemotactic activity on granulocytes, probably due to the generation of C3a/C5a which could be detected in serum incubated with anti-GD3 loaded SK-Mel-28 cells. Both compounds could also be detected in vivo in the plasma of patients suffering from neuroblastoma during therapy with anti-GD2 antibodies. In another set of experiments mAb-GO conjugates generating high amounts of H2O2 in the presence of glucose were bound to these tumor cells. A significant lipid peroxidation could be observed in the simultaneous presence of iron and ascorbate. The lipid peroxidation products were measured as thiobarbituric acid-reactive substances (TBARS) and were also shown to induce chemotactic effects on granulocytes.

ABO Blood-Group System↗
PubMed1994

Activation of cellular cytotoxicity and complement-mediated lysis of melanoma and neuroblastoma cells in vitro by murine antiganglioside antibodies MB 3.6 and 14.G2a.

Mouse monoclonal antibodies against tumour-associated gangliosides GD2 (14.G2a) and GD3 (MB 3.6) were tested to mediate antibody-dependent cellular cytotoxicity (ADCC) with various effector cells or complement-dependent cytolysis (CDC). We also evaluated the immunomodulating potential of interferons in combination with cellular cytotoxicity. Using effector:target (E/T) ratios of 40:1, ADCC with effector cells such as granulocytes or mononuclear blood cells was not detectable against melanoma cell lines GR, SK-MEL-28 and G-361 which preferentially express GD3 and bind antibody MB 3.6. Neuroblastoma cell line SK-N-LO, which was used for comparative purposes, mainly expressed GD2 and the tumour cells were killed effectively after labelling with antibody 14.G2a. Granulocytes did not show significant killing of melanoma cells by ADCC, but neuroblastoma cells were killed very efficiently. Peripheral blood mononuclear cells (PBMC) also failed to kill melanoma cells. Interferon-beta slightly stimulated PBMC and increased killing of neuroblastoma cells, but no additive effects with ADCC were detectable. Incubation of target cells with interferons produced no significant differences in susceptibility of the target cells to interferon-activated PBMC cytotoxicity. Despite the lack of effectiveness in mediating cellular cytotoxicity, GD3 antibody MB 3.6 showed strong complement-dependent cytolysis in the presence of human plasma. There were remarkable differences in individual activity and different susceptibility of the melanoma cell lines. We assume that CDC may have more activity against melanoma cells than cytotoxicity associated with various effector cells.

Animals↗
PubMed1994

Anti-proliferative activity of natural interferon-alpha, isotretinoin and their combination varies in different human melanoma cell lines.

Natural interferon alpha (nIFN-alpha) isotretinoin and their combination were tested for their capacity to modulate the proliferation of different human melanoma cell lines. Modulation of cell growth was measured using the MTT-assay. Isotretinoin and nIFN-alpha as single agents inhibited the proliferation in a dose dependent manner in the three cell lines: SK-Mel-30, SK-Mel-28 and MaRi. The combination of isotretinoin and nIFN-alpha led to a marked enhancement of the antiproliferative effect compared with either nIFN-alpha or isotretinoin alone in SK-Mel-30 cells. In contrast, there were no additive effects on growth inhibition of melanoma cell lines SK-Mel-28 and MaRi when nIFN-alpha and isotretinoin was combined. In one melanoma cell line (MaRi) proliferation was actually enhanced by isotretinoin in combination with nIFN-alpha. These results demonstrate the heterogeneous response of human melanoma cell lines to noncytotoxic concentrations of isotretinoin and nIFN-alpha alone and in combination.

Cell Division↗
PubMed1992

Determination of 2'-5'-oligoadenylate synthetase in serum and peripheral blood mononuclear cells before and after subcutaneous application of recombinant interferon beta and gamma.

The interferon-inducible enzyme, 2'-5'-oligoadenylate synthetase, was estimated in healthy donors and in patients before and after subcutaneous application of recombinant interferon beta and gamma. Tests were carried out with lysates of peripheral blood mononuclear cells, using an established radioenzymatic assay, and in serum samples, using a new radioimmunoassay. Both test systems substantially yielded the same results: after a single injection of interferon beta (1-5 x 10(6) IU), 2'-5'-oligoadenylate synthetase increased in a dose-dependent manner reaching maximal catalytic concentrations in most patients after 24-48 hours (leukocytes) and 48-72 hours (serum). In contrast, interferon gamma (2-4 x 10(6) IU) caused only a small induction of 2'-5'-oligoadenylate synthetase. However, daily application of interferon gamma for 7 days led to a distinct time-dependent increase of 2'-5'-oligoadenylate synthetase activity concentration during this observation period. Characteristically, even during daily application, the 2'-5'-oligoadenylate synthetase activity concentration dropped just 48-72 hours after the first injection of interferon beta. The determination of 2'-5'-oligoadenylate synthetase proved to be useful for optimizing and monitoring subcutaneous therapy with interferon. The new radioimmunoassay which allows the determination of this enzyme in serum is superior to other methods used in the past.

2',5'-Oligoadenylate Synthetase↗
PubMed1992

[Condylomata acuminata in children--detection of HPV 6/11 and 2. Local therapy with interferon-beta hydrogel].

Four cases of genital warts in children (girls) are reported. HPV 6/11-DNA was identified in two cases, and HPV 2-DNA in one. In one case no virus identification was possible. The clinical features of the HPV 2-induced genital warts showed the typical morphology of condylomata acuminata. The mode of transmission of the virus, in absence of sexual contact, could not be explained. The HPV 2-associated genital warts might have been transmitted by autoinoculation from warts on the hands. Topical treatment with IFN-beta-hydrogel was applied over 8 weeks, either as single-agent therapy (1 case) or as adjuvant therapy after removal of the condylomata (3 cases). No remission was seen with the single-agent therapy. In one case the genital warts reappeared after adjuvant therapy, but in the other two cases no recurrence was seen.

Administration, Topical↗
PubMed1992

[Intralesional therapy of melanoma metastases with recombinant interferon-beta].

In ten patients with metastasizing melanomas, discontinuous intratumoral treatment with recombinant interferon beta (rIFN-beta) was administered into 19 cutaneous or palpable subcutaneous metastases. Among the 16 metastases treated with 5 x 10(6) IU per injection, 8 showed partial or complete remission. No recurrence was observed during the 4-9-month follow-up period. There was no regression in 3 metastases treated with 3 x 10(6) IU rINF-beta per injection. No systemic antineoplastic effects were observed in any of the cases. The IFN-beta serum levels were measurably increased following intratumoral application. Local treatment led to a significant increase in (2'-5')oligoadenylate synthetase in the mononuclear blood cells and in the serum. Side-effects of the treatment were moderate; there was a temporary increase in transaminases, a decrease in thrombocytes and influenza-like symptoms. The results show that IFN-beta has a dose-dependent antitumour effect on malignant melanomas.

Adult↗
PubMed1991

[Condylomata acuminata--topical and systemic interferon therapy].

An open study was carried out to test the effect of systemic administration of interferon (IFN) gamma and local application of IFN beta as monotherapy and adjuvant treatment. The topical application of IFN beta gel had no effect as monotherapy and when it was given as adjuvant therapy the rate of recurrence was not significantly reduced. IFN gamma was given for monotherapy in two different doses (100 and 200 micrograms per s.c. injection). The response rate to the cyclic treatment was 45% in the group (20 patients) receiving a dosage of 100 micrograms, and 57% in the group (26 patients) receiving a dosage of 200 micrograms. Patients with a duration of the disease longer than 18 months and patients with immune deficiency did not respond to the monotherapy. A group of 15 patients with resistant genital warts received adjuvant treatment with IFN gamma over 7 days after surgical treatment. In patients with inconspicuous immune status it was possible to reduce the recurrence rate.

Condylomata Acuminata↗
PubMed1990

[Giant condyloma (Buschke-Löwenstein) of the vulva].

Diagnosis, therapy and biological behaviour of the Buschke-Löwenstein tumour of the vulva are described. Surgical treatment is accompanied by an antiviral therapy with interferon. Viral genesis of HPV 6 and/or HPV 11 is probably the cause of this intermediate tumour a type between condyloma and invasive squamous cell carcinoma.

Aged↗
PubMed1990

Treatment of psoriasis and psoriatic arthritis with interferon gamma.

In a placebo-controlled double-blind randomized study, 24 patients with psoriatic arthritis were given 28 d of treatment, and in an open study, 56 patients were treated for 9 months. We treated patients with 100 micrograms IFN gamma per subcutaneous injections, which were given daily for the first 2 weeks and then 3 times per week. The principal criterion for evaluation of therapeutic success on arthritis was improvement of the Ritchie joint pain index by at least 25% in the double-blind and 30% in the long-term study. In the double-blind study, the interferon arm was superior to the placebo arm with a statistically significant, one-side error probability of less than 5% in the chi-square test. In the long-term study, IFN gamma caused an improvement in a portion of patients in the first 3 months of therapy. No further improvement was observed after the third month, and patients classified as responders in the first months showed a deterioration of the disease by continuing treatment. The humoral inflammatory parameters did not normalize during therapy. Regression of the skin manifestations could not be observed. IFN gamma is evidently capable of inducing a psoriasis on the injection site. Investigations of IFN gamma serum levels, IFN antibodies, 2'-5' A synthetase levels in serum, and mononuclear blood cells and NK cell activity under long-term therapy showed no explanation for the loss of efficacy after 3 months treatment.

Arthritis, Psoriatic↗
PubMed1990

Psoriasis induced at the injection site of recombinant interferon gamma. Results of immunohistologic investigations.

Recombinant human interferon gamma used for treatment of psoriatic arthritis was found to induce expression of HLA-DR, but not HLA-DP or HLA-DQ, on keratinocytes at the site of injection. Some patients showed an improvement of their joint symptoms, but the cutaneous manifestations remained unaffected. In 10 of 42 patients, punctiform psoriatic foci could be induced at the site of injection of interferon gamma. For this presentation, we selected a female patient with psoriatic arthropathy and type II diabetes mellitus in whom psoriasis was induced at the site of application of interferon gamma, but not after subcutaneous injection of insulin or placebo. We conclude that interferon gamma is an important lymphokine in the development of psoriasis.

Abdomen↗
PubMed1990

[Virus-induced papilloma of the conjunctiva. Detection of HPV 6a DNA].

By means of hybridization of nucleic acid, we detected DNA specific for papilloma virus, type 6a, in a caruncle papilloma of a 45-year-old female patient suffering from genital warts. These findings show that papilloma viruses, which are usually responsible for genital warts, may also induce conjunctival papilloma.

Condylomata Acuminata↗
PubMed1989

Lysis of neuroblastoma cells by the ADCC-reaction: granulocytes of patients with chronic granulomatous disease are more effective than those of healthy donors.

Granulocytes from healthy donors lyse human neuroblastoma cells in the ADCC-reaction using antibody MAb 14.18 directed to ganglioside GD2 present on the surface of most neuroblastoma cells. Addition of catalase, superoxide dismutase and azide do not impair this process. Granulocytes from patients with chronic granulomatous disease (CGD) kill neuroblastoma cells even better than those collected from healthy donors. These results indicate that reactive oxygen intermediates (ROI) are not involved in killing of neuroblastoma cells using MAb 14.18, and that granulocytes from patients with CGD may compensate for defects in generation of reactive oxygen intermediates by more effective oxygen-independent killing mechanisms. One patient with CGD was treated with interferon-gamma. During and after treatment, generation of ROI could not be detected and neuroblastoma cell killing was not significantly altered.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1989

Immunohistology of genital warts in different stages of regression after therapy with interferon gamma.

Twenty patients with papillomavirus-induced genital warts received pulsatory treatment with interferon gamma by subcutaneous injections in the abdominal skin. The condylomata regressed completely in 11 of the 20 patients analyzed. Sequential biopsies taken from genital warts and nonlesional skin were investigated by immunohistological techniques with the use of monoclonal antibodies against differentiation and HLA antigens to evaluate immunological effector mechanisms of condylomata regression. In all responders regression was shown to be associated with increasing dermal and epidermal infiltrates of activated CD4 and CD8 T lymphocytes, as well as with aberrant expression of HLA-DR and/or DY antigens on keratinocytes. Thus alteration of HLA class II antigen expression on keratinocytes in the presence of T lymphocytes is an important criterium for regression of genital warts.

Condylomata Acuminata↗
PubMed1989

[Condylomata acuminata gigantea with detection of HPV-6-DNA. A case report with adjuvant systemic IFN-gamma therapy].

A case history of a 65-year-old man with giant condylomata (Buschke-Loewenstein tumour) of 30 years' duration is presented. The lesions were histologically confirmed, there were no signs of metastatic spread. HPV 6a DNA has been identified in Buschke-Loewenstein tumours and in different types of papilloma. After surgical removal in several sessions and treatment with gamma interferon by subcutaneous injection into the abdominal skin the patient has remained almost free of lesions.

Aged↗