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Biomedical subjects

G Rassner

Publications and source records attributed to G Rassner.

At least 91 records · Page 5Linked to original sources
PubMed1994

[Position and recommendations of the Malignant Melanoma Committee of the German Society of Dermatology on diagnosis, treatment and after-care of malignant melanoma of the skin. Status 1993/94].

The Melanoma Committee of the German Dermatological Society has prepared this position paper on prognostic factors, classification and clinical staging of cutaneous malignant melanoma and has recommended guidelines for diagnosis, treatment and follow-up. The aim is to achieve a consensus procedure for dealing with this tumour.

Aftercare↗
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

[Significance of cutaneous microangiopathy for the pathogenesis of dermatitis in venous congestion due to chronic venous insufficiency].

Skin damage due to chronic venous insufficiency is preceded by severe microangiopathy of skin. With increasing clinical symptoms like edema, hyperpigmentation, induration, ulcer and atrophy blanche number of nutritive capillaries and transcutaneous oxygen-tension decreases, transcapillary, and interstitial leakage increases and cutaneous vascular reserve disappears. These congruent results were found by means of capillaroscopy, fluorescence-videomicroscopy, transcutaneously measured oxygen partial pressure and Laser Doppler Fluxmetry. Most of capillaries are elongated and tortuous, especially in ulcer stage they look glomerular. Compared to pin-shaped capillaries glomerular capillaries contribute less to nutrition because of functional AV-shunts. As dilated capillaries are already seen in skin areas without any trophic skin changes, cutaneous microangiopathy seems to be first consequence of venous hemodynamic disturbances which then is followed by skin disease. As severe microangiopathy still remains after healing of ulcer, it explains frequent recurrencies.

Blood Flow Velocity↗
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↗
PubMed1993

Epidermolysis bullosa acquisita: efficacy of high-dose intravenous immunoglobulins.

A 16-year-old boy had a 6-year history of a generalized bullous eruption that was resistant to multiple therapies. Findings of immunofluorescent split-skin studies and electron microscopy were consistent with a diagnosis of epidermolysis bullosa acquisita. Treatment with cyclosporine and prednisolone decreased new blister formation. Additional therapy with high-dose intravenous immunoglobulins was successful in controlling the patient's disease.

Adolescent↗
PubMed1992

Demonstration of proteases in basal cell carcinomas. A histochemical study using amino acid-4-methoxy-2-naphthylamides as chromogenic substrates.

BACKGROUND: Proteases are reported to play an essential part in the proliferative, invasive, and metastasizing behavior of malignant tumors. The aim of the current study was to determine the activity and localization of proteases in basal cell carcinomas (BCC) histochemically. METHODS: Various proteases were identified histochemically in frozen sections of BCC. The following amino acid-4-methoxy-2-naphthylamides (MNA) were used as chromogenic substrates:alanine-MNA for the detection of aminopeptidase M (APM), glycyl-proline-MNA for dipeptidyl peptidase IV (DPP IV), lysyl-proline-MNA and lysyl-alanine-MNA for dipeptidyl peptidase II (DPP II), glycyl-arginine-MNA for dipeptidyl peptidase I (DPP I), and carbobenzoxy (CBZ)-arginyl-arginine-MNA for cathepsin B. RESULTS: APM activity was high in the peritumorous connective tissue, whereas the tumor epithelium and epidermis had negative results. DPP IV showed a highly positive reaction in both tumor epithelium and surrounding connective tissue. Cathepsin B and DPP I reacted strongly in the tumor epithelium but not in the peritumorous connective tissue. CONCLUSIONS: The marked activity of APM, DPP IV, DPP I, and cathepsin B may be related to the proliferation and invasive growth of BCC. The distribution of the activity of APM and DPP IV indicates dynamic interactions between the tumor epithelium and the adjacent connective tissue in the neoplastic process.

2-Naphthylamine↗
PubMed1992

The prognosis of primary and metastasising melanoma. An evaluation of the TNM classification in 2,495 patients.

The prognostic value of the TNM classifications of the UICC dated 1978 and 1987, was investigated in a population of 2,495 patients who were followed up over the long term. In the case of primary melanoma, Breslow's tumour thickness proved to be the most powerful predictor of patient survival in multivariate analysis, while the significance of Clark's level ranged after that of both localisation of the primary tumour and the sex of the patient. The continuous proportional relationship between tumour thickness and risk of death makes it possible to regrade thickness groups. Grading cutoffs at 1, 2 and 4 millimetres, with no account being taken of depth of invasion, proved to be particularly favourable for a classification in accordance with prognostic criteria. In advanced stages of the disease, the outcome of locoregional and distant metastasis is significantly different; and furthermore in the case of locoregional metastasis, in-transit and satellite metastases exert a significantly better prognosis than regional lymph node involvement. Isolated juxtaregional lymph node metastases occurred primarily or during the course of the observation period in only 19 patients of our group, and, in comparison with visceral metastases, proved to have only an insignificantly better prognosis. For this reason, it would appear meaningful to assign them to a common stage. On the basis of these results, proposals are made for modifications of the TNM classification.

Evaluation Studies as Topic↗
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

[Neuron-specific enolase (NSE)--a suitable tumor marker in malignant melanoma?].

The neuron-specific enolase (NSE) level is elevated in neurons and in numerous cells of the APUD system; melanocytes are also considered to belong to this system. In order to test the relevance of NSE as a tumour marker for malignant melanoma, its concentration in serum was radioimmunologically determined in 89 patients with melanomas: 24 in stage I (primary tumours), 44 in stage II (regional metastases), and 21 in stage III (distant metastases). The average (+/- coefficient of variation) concentrations recorded were 7.4 micrograms/l (+/- 46%) in patients in stage I, 5.8 micrograms/l (+/- 32%) in those in stage II, and 11.0 micrograms/l (+/- 72%) in those in stage III. A threshold value of 11.5 micrograms/l was exceeded in 9 cases, including 8 patients in stage III. Since definitely increased values arose almost exclusively in distant metastases, determination of NSE levels in serum is hardly a suitable tool for early detection of latent metastases.

APUD Cells↗
PubMed1992

[Quantitative analysis of recurrence and spontaneous regression of basalioma parts left in situ].

To some extent, parts of basalomas found remaining in situ following tumour excision tend to spontaneous regression. This is a well-known phenomenon and has significance for the recurrence of incompletely excised tumors. The present study involved a quantitative investigation of the relationship between recurrence and spontaneous regression. Following precisely defined excision of basalomas, the entire exterior of the excised material was examined by contrast microscopy in HE-stained paraffin sections (3-dimensional histology). Whenever tumour outgrowths were found, it was possible to document exactly their type, localization, extent, and depth of invasion. In 66 such cases no follow-up operation was performed, but only a follow-up examination after a minimum of 31 and a maximum of 113 months (average: 60 months). Only 50% of these undisturbed tumour outgrowths resulted in a recurrence during the follow-up period. A very high rate of spontaneous regression (71%) was found among the solid tumour outgrowths, but a significantly lower rate (19%) among the fibrosing tumours. Moreover, regression was dependent on the tumour remnant's mass and the clinical diameter of the tumour removed. It was independent of the depth of infiltration. Although the rate of spontaneous regression of tumour outgrowths persisting after therapy is relatively high, it cannot be predicted in individual cases. It is not possible to be certain that tumour removal has been achieved unless micrographic surgery has been continued until complete absence of tumour is proved. In all procedures that are not subsequently monitored, an unacceptably high rate of recurrence must be expected, especially in the case of fibrosing basaloma. This is commented on at length.

Aged↗
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

Destruction of tumour parenchyma in basal cell carcinoma by tumour-associated neutral proteases: a histochemical study.

Proteolytic activity was demonstrated histochemically in frozen sections of basal cell carcinomas (BCCs). After incubation of tissue sections in 0.1 M phosphate buffer with 0.25 M NaCl the tumour epithelium was almost completely destroyed. The basal and squamous cell layers of the epidermis disintegrated to varying degrees, particularly where they were directly in contact with tumour epithelium. Serine and metalloprotease inhibitors diminished this tissue destruction. Iodoacetate enhanced tumour destruction, urea and potassium thiocyanate even more so. The high proteolytic activity of BCC demonstrated in this study may be an important factor in the proliferative, invasive and destructive behaviour of this tumour.

Basal Cell Carcinoma↗
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↗