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Biomedical subjects

G Ghyka

Publications and source records attributed to G Ghyka.

At least 37 records · Page 2Linked to original sources

Human leukocyte interferon treatment associated with IL-2 in the non-AIDS related Kaposi's sarcoma.

Patients with classical European Kaposi's sarcoma have been treated by intra- and peritumoral injections of human alpha-leukocyte interferon (IFN) (12 cases) or alternatively with IFN and naturally synthetized IL-2 (8 cases). All the patients were HIV negative their tumour appearing at least six months before. In each patient one tumour received 1 ml (50,000 IU) IFM alone or associated, alternatively with 1 ml IL-2, twice a week during 4-6 weeks, whereas another nodule situated 8-10 cm apart was considered as control and remained uninjected. The clinical follow-up revealed that in the same patient in the same anatomical area the treated nodule was cured in all the investigated cases while the untreated nodule was not. These data undoubtedly prove that IFN is the responsible factor for the involution and final cure of the Kaposi tumours treated by perilesional inoculations. Association with IL-2 (and certainly also other interleukins) increases the beneficial clinical effect activating the tumour involution. The histological examination showed that important histopathological changes occur in the treated nodules, i.e., complete disappearance of the Kaposi's aspect; fibrosclerous modifications progressively replacing the abundant fibroblastic cells characteristic of Kaposi's tumour; abundant infiltrations of leukocytes especially lymphocytes; necrotic patches often appearing along with hemorrhagic centers. IL-2 association seems to frequently induce especially this last type of histological phenomena.

Adult↗

Immunoelectrophoretic study of Sendae virus envelope antigens with hyperimmune sera prepared in different laboratory animals.

At similar HAI titers rabbit sera reveal a larger number of fractions (ten) in immunoelectrophoretic analysis of Sendai virus envelopes than do guinea pig sera, which only yield three distinct fractions. These differences are observed in both rocket and crossed immunoelectrophoresis, and are more marked in the latter. The number of fractions revealed does not differ in relation to the antigen used for hyperimmunization (intact Sendai virus, Triton-disrupted virus or envelope fractions extracted by Triton or Tween-ether). Solubilized Sendai virus envelopes obtained by Tween-ether or Triton treatment contain host antigens in their structure, the same as intact virus.

Animals↗

Immunoelectrophoretic study of the host antigens of Sendai virus cultivated in different substrates (embryonated hen eggs and KB cells). Note I. Analysis of chorioallantoic membrane host antigens.

The immunoelectrophhoretic analysis of two preparations of the same virus cultivated in different substrates (Sendai/egg and Sendai/KB) demonstrate that virus envelopes contain: a) identical virus-specific antigens (but also some virus antigens with only partial immunochemical identity, or even non-identity); b) antigens incorporated by the virus from the host cell, during assembly and release. The latter differ according to the host, and some of them are only partially identical with the corresponding antigens of the host cell, which suggests that host cell glycoproteins are incorporated into the virus envelope after certain virus-induced modifications.

Animals↗

Immunoelectrophoretic study on the host antigens of Sendai virus cultivated in different substrates (embryonated hen eggs and KB cells). Note II. Analysis of KB cell host antigens.

It could be demonstrated by immunoelectrophoretic analysis that the host antigen incorporated in the envelopes of Sendai virus cultivated in KB cells (Sendai/KB) is characteristic of these cells and does not occur in the envelopes of the same virus grown in the embryonated hen egg (Sendai/egg). This host antigen appears from the first passage in KB cells and is constantly maintained over subsequent passages. The glycoproteins released by Triton X-100 disruption from Sendai/KB envelopes have a concomitant antigenic specificity for both virus and host. In the case of Sendai/egg virus, exclusively virus-specific macromolecules are also released.

Antigens↗

The effect of human alpha leukocyte interferon (IFN) on the frequency of sister chromatid exchanges (SCE) in the KB cell line.

Concentrations of 50, 500 and 5,000 iu/ml of natural human alpha leukocyte interferon (IFN) were added into the culture medium of KB cells, 4 h after serial passage, in the presence of 5-bromo-desoxyuridine (Brdu) at 10 micrograms/ml. Similar cultures without IFN were set up as controls. After 72 h of incubation, the harlequin technique (differential staining of sister chromatids) was applied in order to discriminate among the metaphases of different generations and to appreciate the frequency of sister chromatid exchanges (SCE) in the second generation cells. The incidence of sister chromatid exchanges was slightly increased following IFN treatment but no dose-effect relationships were observed. At the same time, cell cycle kinetics estimated as replication index (RI) and average generation time (AGT) was not modified in IFN-treated cells as against the controls.

Cell Division↗

S-phase detailed analysis in KB cells by bromdeoxyuridine labelling.

A method based on the sequential BrdU incorporation followed by differential spiralization of the chromosomes was used for analysis of S-phase in KB cells when Brdu was added to the cultures for 19, 24 and 26 hours before fixation. The S-phase was subdivided into three subphases, each recognisable by a specific incorporation pattern at metaphase: late-S (LS), middle-S (MS) and early -S (ES). Two other intermediary subphases, mid-early S (mES) and mid-late S (mLS) have also been distinguished but their accurate identification is generally difficult. A high degree of asynchrony in KB cells population was observed as well as a wide variability concerning the duration of S-phase (BrdU = bromdeoxyuridine).

Bromodeoxyuridine↗

The role of tumor angiogenesis factor (TAF) in the tumor growth. Pathological aspects.

This work was carried out on control and immunosuppressed A2G mice inoculated with murine tumour cells (Ehrlich ascites) and human ones (KB cell line). The growth of the tumours was conditioned by the growth of the fibrovascular stromas as a response of the host organism to the TAF secretion. This process is a nonimmunological response, the differences between control and immunosuppressed mice being of no statistical significance.

Angiogenesis Inducing Agents↗

Study of host antigens in the envelopes of different myxo- and paramyxoviruses cultivated in the embryonated hen egg.

By immunoelectrophoretic analysis it was shown that different viruses--such as myxo- (influenza A0PR8) and paramyxoviruses (Sendai, SV5, NDV, mumps)--cultivated in the same host cells (chorioallantoic membranes) incorporate similar host antigens into their envelopes. The amount of host cell antigens incorporated into the virus envelopes differs from one virus to another. The fact that incorporation of host cell antigens occurs only after a virus-induced modification seems to be a general characteristic of enveloped viruses such as myxo- and paramyxoviruses.

Animals↗

Study of cell surface antigens induced by herpes simplex virus. Note I. Identification of the antigens by means of protein A-containing staphylococci.

A rapid, easy-to-perform and specific technique for the visualization of herpes simplex virus (HSV)-induced cell surface antigens is described. The technique consists in the incubation of HSV-infected cells with hyperimmune HSV antiserum and formation of rosettes with FITC-labelled Cowan strain staphylococci containing protein A. The "nonspecific background" of the reaction can be estimated by comparison with the rate of bacteria binding by control cells not incubated with HSV antiserum.

Antigens, Surface↗

Intralesional human leukocyte interferon treatment in the non-AIDS related Kaposi's sarcoma.

Twelve patients with classical European Kaposi's sarcoma have been treated by intra- and peritumoral injections of human alpha leukocyte interferon (IFN)--Ginterferon ("V. Babeş Institute", Bucharest). All the patients were HIV negative their tumour appearing at least six months before. In each patient one tumour received 1 ml (50,000 IU) IFN twice a week during 6-7 weeks whereas another nodule considered as control remained uninjected. After treatment biopsies of both the IFN-treated and the untreated nodules were performed in 8 patients and histological examinations were carried out. The clinical follow-up revealed: The skin colour progressively changed from purple red to dark reddish or even brown in all the IFN-treated tumours and only in 3 of the untreated ones (p less than 0.001). The consistency of the nodules decreased in all the treated tumours and only in 2 of the untreated ones (p less than 0.001). The tumour thickness decreased in 9 of the treated tumours and in none of the untreated ones (p less than 0.001). The surface of the lesions decreased in 4 of the treated nodules but not in the untreated ones (p less than 0.05). The IFN-inoculated tumours were gradually cured even in the four cases in which during the treatment some other tumour progressed or even new lesions appeared. The histological examination showed that: all the IFN-treated tumours were either predominantly sarcomatous or predominantly angiomatous. The typical Kaposi aspect disappeared totally in 2 of the cases examined, and in 3 a fibrosclerotic massive change was obvious.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

Diagnostic value of serum interferon level in systemic lupus erythematosus.

In all the patients with systemic lupus erythematosus (SLE) tested in the active phase of the disease the serum interferon (IFN) level increases above the normal value (20 I.U./ml) reaching in some cases 80-160 I.U./ml. The detection of this increased level of IFN is useful to discriminate if some diseases such as glomerulonephritis or hemolytic anemias develop as part of a systemic auto-immune disorder since in such pathologic conditions lacking auto-immune mechanisms the serum IFN level is not increased. The detection of the serum IFN level proved to be a useful test in the follow-up of the clinical evolution as well as for the efficiency of the immunosuppressive therapy since in all the investigated cases IFN level decreased to normal after Cortisone administration concomitantly with the clinical remission of the disease. The above described data support the assumption that in the pathogeny of auto-immune diseases, SLE in our case, there are some initial cell-mediated auto-immune phenomena such as cell-mediated auto-cytotoxicity leading to a massive activation of the CTL and NK cells and consequently to the over-production of some lymphokines such as IFN.

Autoimmune Diseases↗

Interferon efficiency in the treatment of herpetic dermatites. II. Comparison between human leukocyte interferon (Ginterferon) and a recombinant interferon (Roferon).

The comparative efficiency of a recombinant interferon-Roferon (R-IFN) and a human, naturally synthetized interferon-Ginterferon (G-IFN), applied as ointments in the treatment of herpetic dermatites, was studied in a blind trial. It was found that R-IFN in doses of 20,000 IU/g has practically similar results as G-IFN in doses of 10,000 IU/g therefore half the dose of the former product. Thus both preparations reduced significantly the mean duration of a herpetic dermatitis attack and both proved more efficient on smaller lesions (less than 2 sq.cm) than on larger ones (over 2 sq.cm). Likewise with both preparations the reduction of the healing period was more marked when administered in the first 2-3 days after onset. It was also found that the arrest of new vesicle appearance after two days of treatment is a reliable clinical criterion for the estimation of IFN capacity to block effectively viral multiplication in the host's epithelial cells. Finally the efficacy of both R-IFN and G-IFN proved similar whatever the localization of disease (oral or genital) or in their capacity to prevent relapses or the appearance of bacterial complications.

Clinical Trials as Topic↗

An experimental model comparing the antineoplastic and the immunosuppressive effects of some cytostatics.

An experimental model evaluating comparatively the antineoplastic and the immunosuppressive effects of some cytostatics (cyclophosphamide and vinblastine) is described in the present paper. Different cytostatic doses were intraperitoneally administered in mice which were 24 hours later grafted with a suspension of human tumoral KB cells. The xenograft acceptance was macroscopically and microscopically recorded 21 days later. By the Reed and Muench method and also by graphical extrapolation the LD50 (lethal dose for 50% animals) and the TD50 (the immunosuppressive dose enabling 50% animals to accept the xenografts) could thus be determined for both cyclophosphamide and vinblastine. The number (percent) of the tumour bearing animals three weeks after grafting was considered as an indicator of the cytostatic dose at which the immunosuppressive effect exceeded the antineoplastic effect. The in vitro effect of the same drugs on the KB cells was tested by inoculating different cytostatic doses in the cell cultures and counting at different time intervals the adherent as well as the nonadherent cells. The in vitro drug toxicity on the KB cell cultures was also determined by the trypan blue exclusion test. Both cyclophosphamide and vinblastine proved to be in vitro highly potent cytostatics i.e. when directly acting on the KB cells. This effect was dose correlated for both the considered drugs. However our in vivo experiments have shown that none of the observed effects when considering the direct action of the cytostatic on the cultured cells could not safely be extrapolated in vivo. Our results have an obvious practical importance when considering the therapeutical approaches in the neoplastic diseases. They demonstrate that the increase in cytostatic dose is not directly correlated to the antineoplastic effect since it reaches a limit at which the immunosuppressive effect highly exceed the tumour growth inhibition effect. The described experimental model could also be used in comparative estimations of the biological effects of different cytostatic drugs possibly referred to a standard immunosuppressive reagent as an antilymphocyte antiserum.

Animals↗

Interferon level in human normal sera.

Interferon (IFN) level in the sera of normal humans was determined by their protective effect on a KB cell culture against the cytopathic effect (CPE) induced by vesicular stomatitis virus. The technique revealed all the three known types of IFN. In the investigated population 15 of 37 sera (40%) were found to protect against the CPE at 1/10 dilution, 11 of 37 (30%) still protect at 1/20 dilution, and 7 of 37 sera (19%) still protect at a dilution of 1/40. No serum was found to have detectable IFN levels at 1/80 dilution. We can thus consider that the normal serum level ranges up to a 1/20 dilution i.e., up to 20 IU/ml. The above titers are slightly higher than the normal IFN level reported by other investigators in other human populations, although no clear reasons can be given to account for the differences.

Adult↗