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Biomedical subjects

G Ghyka

Publications and source records attributed to G Ghyka.

At least 19 recordsLinked to original sources

Intralesional human leukocyte interferon treatment alone or associated with IL-2 in non-AIDS related Kaposi's sarcoma.

Patients with classical European Kaposi's sarcoma were treated by intra- and peritumoral injections of human alpha leukocyte interferon (IFN) (12 cases) or, alternatively, with IFN and naturally synthesized IL-2 (8 cases). All the patients were HIV negative with tumors which had been present for at least six months. In each patient, one tumor received 1 ml (50,000 IU) IFN alone or alternatively associated with 1 ml IL-2 twice a week for 4-6 weeks; another nodule situated 10-12 cm away was considered as a 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; the untreated one was not. These data strongly suggest that IFN is the factor responsible for the involution and final cure of these Kaposi tumors treated by perilesional inoculations. Association with IL-2 (and certainly also other interleukins) increases the beneficial clinical activation of the tumor involution. Histological examination showed that important histopathological changes occur in the treated nodules: complete disappearance of the Kaposi's aspect, fibrosclerous modifications progressively replacing the fibroblasts characteristic of Kaposi's sarcoma, abundant infiltrations of leukocytes, especially lymphocytes and necrotic patches, often with hemorrhagic centers. IL-2 association seems to especially induce this last type of histological phenomenon.

Acquired Immunodeficiency Syndrome

[Immunomodulator effects of 2 kinds of interferon alpha on the in vitro synthesis of systemic and articular interleukin 1 in rheumatoid polyarthritis].

The authors have studied the synthesis of interleukin 1 by articular and circulating macrophages and the effect of two types of interferon alpha (IF) on this synthesis in 20 patients with untreated rheumatoid arthritis (RA). The articular and especially systemic interleukin levels in the RA patients are significantly higher than those of the test subjects. Interferon modifies in a very different way the production of interleukin 1 in the patients and in the test subjects. This is linked with the in vitro experimental conditions as well as the increase in the IL1 levels in the patients. The authors discuss the perspective therapeutics offered by this modulation of interleukin production by interferon.

Adjuvants, Immunologic

Anti-phospholipase C antibodies inhibit the lectin-induced proliferation of human lymphocytes.

A novel approach was used to assess the role of phosphoinositide hydrolysis in the mitogenic action of phytohemagglutinin (PHA) or concanavalin A (ConA). The treatment of human peripheral blood leukocytes (PBL) with monospecific antibodies against phospholipase C (PLC) produced a dose-dependent inhibition (up to 100%) of PHA (10 micrograms/ml) or ConA (25 micrograms/ml) proliferative effects. Thus, the activation of membrane-bound PLC is a sine-qua-non condition for lectin-induced proliferation of T lymphocytes. The key-role of PLC versus protein kinase C (PKC) is stressed by the fact that the inhibition of PKC with Hidaka's compound H-7 (40 microM) produced only a partial blockade (about 25%) of lectin mitogenic effect.

Antibodies

Passive hemagglutination and complement fixation reactions in the early diagnosis of Mycoplasma pneumoniae infections.

Complement fixation (CF) and passive hemagglutination (PHA) tests (the latter with a M. pneumoniae antigen coupled by glutaraldehyde onto red blood cells) were performed in 263 patients with various infectious diseases (mostly in the 1st and 2nd week after onset) and non-infectious ones. CF reaction proved to be inappropriate for the early etiological diagnosis of mycoplasma infections, since the high titers were distributed undifferentially among the various patient groups and many sera (38%) showed anticomplementary activity. A PHA titer of at least 1/128 (preferably of 1/512) points to the presence of a M. pneumoniae infection, especially if clinical, radiological and laboratory data suggest a nonbacterial or mixed pneumonia. The diagnosis is often early enough to orientate the etiological therapy towards macrolides and tetracyclines. The PHA reaction recommended is specific, sensitive, reproducible and easy to perform.

Complement Fixation Tests

Highly active effect of alpha interferon in blocking the cutaneous delayed hypersensitivity.

A group of 13 patients with contact dermatitis to various chemical compounds such as potassium dichromate, nickel sulphate, formaldehyde and balsam of Peru, was investigated by patch test and by the agreement between the history of disease and the patch test, the specific allergen involved in each special case could be demonstrated. Two-three days after the first patch test three normal skin areas were chosen. The first area was intradermally infiltrated with alpha-2a Interferon (IFN) (100,000 I.U. in 1 ml), the second area was infiltrated with saline and the third area, considered as control, did not receive any treatment. Once more the corresponding allergen was applied into the skin in a second patch-test. After 48 hours in the IFN infiltrated area, only the delayed contact hypersensitivity become negative thus proving that alpha-2a IFN behaves as an efficient inhibitor of these immune effector reactions. Since the lymphocytes involved in the delayed type hypersensitivity reactions (in our case contact dermatitis) belong to the T helper line, i.e., are CD-4 positive cells we conclude that alpha-2a IFN in vivo is an efficient inhibitor of the activation of these cells. This effect achieved by any CD-4(+) DTH clones does not depend on their antigenic specificity. Some clinical trials are now in progress in our laboratory to turn to account this important biological effect in the clinical practice as an efficient inhibitor in skin contact dermatitis.

Adolescent

Therapeutic effect of intralesional interferon (Roferon) in squamous cell carcinoma.

Recombinant alpha-2 interferon (IFN)--Roferon--100,000 IU/ml was intralesionally administered in 8 cases of squamous cell carcinoma (SCC) three times a week during 4-6 weeks in inoculations of 1 ml each. The therapeutic effect was scored as major--more than 60% reduction of the tumor size, moderate--30-60% reduction of the tumor mass and, nonreactive--less than 30% reduction of the tumor size. Three cases showed a major reduction, three showed a moderate reduction and two patients showed no reduction of the tumor volume. Histopathological examination of the surgically removed tumors after completion of the Roferon administration confirmed the clinical diagnosis of squamous cell carcinoma and revealed that an intense leukocyte, mainly lymphocytes, infiltration can be observed along with necrotic centers, progressively surrounding and reducing in size the tumor islets, thus proving an intense activation of the immune effector reactions against tumor cells.

Carcinoma, Squamous Cell

Correlation of serum interferon with some clinical and humoral signs of systemic lupus erythematosus.

The serum level of total interferon (IFN) was measured in 15 male patients with systemic lupus erythematosus (SLE) in the active phase and in remission, before and during corticotherapy. The values found were correlated with the clinical and humoral signs of disease. The IFN titer was high in the active phase of disease and was correlated with fever, extension of skin rash, polyarthritis, myositis, autoimmune hemolysis, cardiac and cerebral involvement as well as with ESR, reacting protein C, CIC, ANF and the percentage of LE cells. Isolated LE nephropathy without rapidly progressive or advanced renal failure was not associated with high IFN titer.

Adult

Further immunological evidence for the presence of Fc receptors on the surface of HSV-infected cells.

By coupling passive hemadsorption (PHads) reaction with a complement-mediated cytotoxicity test (CT) it is possible to detect the presence on the surface of hamster embryo fibroblasts of Forssman antigens, hindering the demonstration by PHads of the receptors for the Fc-fragment of immunoglobulins (FcR), possibly induced by herpes simplex virus (HSV). These antigens are acetone- and formol-resistant, but they are destroyed by treatment with methanol or ethanol. However, CT with anti-sheep RBC serum performed in HSV-infected monkey kidney cells is always negative, which proves that the attachment of immunoglobulins to these cells occurs exclusively through their Fc-fragments.

Animals

Immunoelectrophoretic characterization of Sendai virus antigens.

Antigens extracted from Sendai virus by solubilization with Triton X-100 (Tx). Tween-20 (Tw) or Triton X-100 and SDS (Tx-SDS) were analysed by rocket, crossed and tandem immunoelectrophoresis. The migration of these antigens through 1% agarose supplemented with guinea pig anti-viral envelope protein anti-serum shows that Tx and Tw antigens consist of three fractions differing in their quantitative ratios, while Tx-SDS exhibits five different fractions. The method proved to be useful for the identification of anti-host antibodies in immune antisera by means of an antigen extracted from the chorio-allantoic membrane of embryonated hen eggs.

Antigens, Viral

Immunoelectrophoretic investigations on Sendai virus envelope antigens in relation to host antigens.

The different antigenic fractions characteristic of egg-cultivated Sendai virus envelopes were studied by immunoelectrophoresis. Virus-specific and host-specific fractions were identified. It was proved that incorporation of the host membrane fragments into the viral envelopes is not a passive phenomenon. During the last stages of its assembly and release, the virus incorporates into the envelopes some host glycoproteins, after an active biochemical processing resulting in a considerable reduction of their molecular weight, while the host antigenic determinants remain almost unaltered.

Animals