Biomedical subjects

S Orbach-Arbouys

Publications and source records attributed to S Orbach-Arbouys.

At least 37 records · Page 2Linked to original sources

PubMed1994

In vivo eradication of Friend virus as an experimental HIV-model, by combination of zidovudine, acriflavine and an ellipticine analogue. Possible application to the treatment of human pre-AIDS?

Simultaneous administration of zidovudine, acriflavine and celliptium to Friend virus-injected mice eradicates the virus, as evidenced by the impossibility of the treated-mouse serum, when injected to virgin recipients, to induce spleen foci formation. An adapted preliminary protocol given to patients in whose p 24 antigen was present in the blood, lead to a considerable reduction of that marker. The cures lasted 3 weeks, and were repeated after 3-week intervals. Since p 24 antigen returns to pre-treatment levels at the end of the interval, research should concentrate on the maintenance of the effect during the interval.

AIDS-Related Complex↗

PubMed1994

Changes in the level of blood suppressor CD8+CD57+ lymphocytes, when HIV-1 p24 antigen reappears in the blood.

Using the marker Leu2 + Leu7 + to detect the CD8 suppressor cells (CD88+CD57+), we have observed that their blood level, which increases after primoinfection, during the latent period, increases still further just before and when the p24 antigen returns and is present in the blood. Its ratio over cytotoxic CD8+ cells remains high during the AIDS period, though the absolute number decreases.

Acquired Immunodeficiency Syndrome↗

PubMed1993

The in vivo effect of ellipticine analogues on the blood concentration of Friend virus: a murine model for studying anti-HIV drugs.

The viremia of a mouse carrying a murine retrovirus, the Friend virus, was taken as a model for screening drugs which could be active on the human HIV retrovirus. Ellipticine and two of its analogues injected ip at appropriate doses drastically reduced the viremia of the Friend virus-injected mice, as measured by transfer of their serum on day 8 of the treatment to secondary recipients and numeration, in the spleens of the latter, of the foci the remaining virus had induced. Since phase I and II trials have already been published (for leukemia treatment), the efficacy of those drugs on HIV-1 positive AZT-resistant patients can be tested directly.

Acquired Immunodeficiency Syndrome↗

PubMed1992

The bactericidal capacity of peripheral blood monocytes from HIV positive patients may collapse very soon after the infection.

The activity of peripheral blood monocytes from HIV positive patients was measured by the intensity of the chemoluminescence those cells emit when they ingest a foreign particle. In most patients (84%) that value was impaired. Such an alteration may occur very early in the course of the disease. The anti-p24 antibody titer was correlated with monocyte phagocytic potential as measured by the chemoluminescent value thus indicating the need for adequate monocyte activity in order to obtain antibody formation. The severity of opportunistic infections that HIV positive subjects may develop is a clear indication that their immune systems are abnormal. The most frequently affected cells are those which bear the viral receptor, the CD4 antigen. Those cells are mainly the helper T cells and monocytes. The monocytes are the immune system phagocytic cells which actively control infections, in part by the release oxidative radicals. Those radicals can easily be measured by the chemoluminescence (CL) the cells emit when they ingest a foreign particle. This study examines the CL emitted by peripheral blood monocytes from HIV-positive and control subjects while they phagocytose opsonized zymosan in vitro and correlates these values with other laboratory parameters.

Blood Bactericidal Activity↗

PubMed1992

Retrospective study correlating clinical infectious history and peripheral blood T-cell subpopulations in cancer, GvH and HIV+ patients.

The CD4+ CD8- inducer helper cell and the CD4- CD8+ cytotoxic/suppressor cell absolute numbers were measured in the peripheral blood of patients with various pathological conditions: with leukemia-lymphomas or solid tumors, patients with bone marrow grafts suffering from GvH, HIV-1 asymptomatic carriers, ARC and AIDS patients. The study was carried out during observation periods when they were not suffering from opportunistic infections and were untreated. In all the groups a decrease of the CD4+ CD8- cell absolute number was observed. In the leukemia-lymphoma and solid tumor bearing patients the CD4- CD8+ absolute value was lower than normal, while in the GvH- and HIV-infected patients, it was significantly higher. The clinical follow-up of each group indicates that GvH, ARC and AIDS patients developed infection in 40-68% of the cases, ie the only groups at risk of infection are those in which the CD4- CD8+ absolute values are high: we suggest that the balance CD4+ versus CD8+ should be considered rather the absolute CD4+ when discussing appropriate use of immuno-regulators.

AIDS-Related Opportunistic Infections↗

PubMed1992

Hepatotoxicity induced by a single ip injection of ruthenium red.

Ruthenium red (RR) has been used as a marker in morphological observations of the glycocalix because it interacts with polyanionic mucopolysaccharides. This fact may explain its agglutinating effect on rat blood red cells following a single 20 mg/kg intraperitoneal injection, which increases with time post-injection. This study was performed to determine whether such an effect was due to a direct effect of the RR on the blood cells, to interference with coagulation, or to the non-specific general toxicity of this dye. Male rats were injected with 20 mg/kg RR ip and the enzymatic and coagulation parameters, plus the liver morphology were examined. Alanine aminotransferase (ALAT) activity was increased at 30, 60 and 120 min, and aspartic aminotransferase (ASAT) activity was increased 60, 120 and 480 min after RR injection. The prothrombin time (PT) and partially activated thromboplastin time (PTT) were significantly decreased, particularly after 60-120 min. The liver had an external granular appearance with clear signs of congestion and oedema, and showed degenerative changes very soon after RR injection. A single administration of RR induces serious functional and structural changes in the liver. Such a toxicity, and these changes must be taken into consideration, particularly with regard to neurological studies.

Animals↗

PubMed1991

Increased phagocytic activity of peripheral blood monocytes after intravenous injection of phospholipase A2 to monkeys.

One of the expressions of the activity of phagocytic cells such as monocytes or macrophages is a burst of increased oxidative activity on stimulation. The free oxygen radicals liberated, mainly O2- and H2O2, lead to chemoluminescence, which is thus a measure of activation. Chemoluminescence also depends on arachidonic acid metabolism, and this depends on phospholipase A2 (PLA2). We modified monocyte activity in monkeys by injecting them i.v. with this enzyme and observed that 30 min after injection, the phagocytic activity of peripheral blood monocytes and the chemoluminescence they emitted was greater than that of controls. We suggest that PLA2 may act as an in vivo immunomodulator in mammals.

Adjuvants, Immunologic↗

PubMed1990

Enhanced production of interleukin 1 by mouse peritoneal macrophages after aclacinomycin administration.

The peritoneal cells of mice injected with aclacinomycin (ACM), an oncostatic drug of the anthracyclin family, were found to secrete more interleukin (IL-1), after two successive 24-h periods of in vitro LPS stimulation than those of control mice. This measured IL-1 production is one of the signs of enhanced macrophage activity. The cells of ACM-injected mice also contained more intracellular IL-1 than those of controls. In contrast, macrophages from ACM-injected mice only increased their IL-1 production after the first 24-h incubation with PMA, and not after the second 24-h incubation. The response to ACM was dose- and time-dependent. We have also compared the IL-1 production by macrophages from mice injected with other anthracyclins, at doses equimolar to that of 4 mg/kg ACM and we have observed that adriamycin, 4'-epiadriamycin and aclacinomycin had similar activity, while THP-adriamycin an daunorubicine were slightly more active. Exploitation of this increased IL-1 production by macrophages could be beneficial in the design of tumor treatment protocols.

Aclarubicin↗

PubMed1990

Pulmonary toxicity of oxygen.

Prolonged exposure to hyperoxia in order to compensate for inefficient ventilation can lead to progressive pulmonary damage and death. Since pulmonary macrophages control bacterial and viral penetration, we studied the effect of hyperoxia on pulmonary alveolar macrophages from newborn and adult rats, kept in air or in a 95% normobaric oxygen atmosphere. The viability of pulmonary alveolar macrophages in bronchoalveolar lavages of newborn rats after 3 d in oxygen was significantly lower than that of newborn rats after 3 days in air. The functional capacity, as measured by the phagocytosis of Candida was similarly affected and these observations mays explain why infections develop. Adult rat macrophages were not sensitive to hyperoxia.

Animals↗

PubMed1990

Phospholipase A2, an in vivo immunomodulator.

Arachidonic acid (AA) can be released from membrane phospholipids by the action of phospholipase A2 (PLA2). There is evidence that unsaturated fatty acids, particularly AA, released from membrane phospholipids are required to activate the respiratory burst of macrophages. The data reported here indicate that peritoneal macrophages harvested 30 min after i.p. injection of PLA2 can phagocytose Candida albicans more efficiently and emit more chemoluminescence (CL) than normal cells when stimulated by zymosan. PLA2 injection also enhances the CL of peritoneal cells from mice already stimulated by immunomodulators such as trehalose dimycolate (TDM), bestatin, or oncostatic drugs such as aclacinomycin (ACM). CL is not sensitive to potassium cyanide (KCN), but is inhibited by catalase, superoxide dismutase (SOD), nordihydroguaiaretic acid (NDGA) and high doses of indomethacin (10(-3) M). In vivo PLA2 treatment stimulates the synthesis of both cyclooxygenase and lipoxygenase derivatives of AA metabolism (PGE2, 6-keto, PGF1 alpha TXB2 and LTC4). Inhibitors of AA metabolism (NDGA, indomethacin) modulate the production of free oxidizing radicals in this experimental model, partly because of their effect on AA metabolism, as determined by the measuring immunoreactive products. However, this work indicates that the effects of these inhibitors, which have been extensively used in CL studies, should be interpreted with caution, since their specificity for AA metabolism is relative.

Adjuvants, Immunologic↗

PubMed1990

Allo-activated CD4+ and CD8+ lymphocyte subsets: new ultrastructural findings based on computer-assisted image analysis.

Primary allo-stimulation induces substantial and differentiated modifications in the development of cytoplasmic organelles of peripheral T-lymphocyte subsets. The present computer-assisted image analysis provides evidence that the CD4+ subset undergoes significant increase in organelle density after stimulation, while the CD8+ subset exhibits a post-stimulation organelle development proportional to the cell size. Each immunological subset contains two distinct patterns of cytoplasmic organization, here defined as type I (containing a few cytoplasmic organelles) and type II (with well-developed synthesis and storage organelles). On the basis of these findings cytologic parameters could be ascribed to a heterogeneous proliferation of functionally distinct T-cell clones in CD4+ and CD8+ subsets.

CD4-Positive T-Lymphocytes↗

PubMed1989

Enhanced activity of peritoneal cells after aclacinomycin injection: effect of pretreatment with superoxide dismutase on aclacinomycin-induced cytological alterations and antitumoral activity.

Peritoneal macrophages from mice injected with aclacinomycin (ACM) (4 mg/kg, i.p.) showed increased functional activity, as assessed by increased antitumoral activity in vitro and in vivo and zymosan-triggered chemoluminescence. They also showed ultrastructural signs of activation (increased number of cytoplasmic organelles), and atypical alterations (giant vacuoles and giant lysosomes containing heterogenous myelinoid bodies, lipofuscine-like substance, cytoplasmic debris, and a fine granular material). As these atypical alterations could be due to the generation of superoxide following ACM injection, superoxide dismutase (SOD) was injected 1 h prior to ACM administration. Neither the morphological characteristics of activation, nor the enhanced metabolic and antitumoral activities induced by ACM were affected by SOD pretreatment, but the atypical alterations were inhibited in a dose-dependent manner. Heat-inactivated SOD did not prevent their appearance. The atypical alterations were not found in peritoneal macrophages from talc or lipopolysaccharide-injected mice, but they were present in Adriamycin-treated mice and were also prevented by SOD pretreatment, indicating that the alterations are due to anthracycline treatment. Finally, [125I]SOD was phagocytized by peritoneal macrophages in vitro and in vivo and not by L1210 tumoral cells, explaining why the atypical alterations induced by ACM were no longer seen after SOD pretreatment. The unchanged direct oncostatic activity of ACM following SOD pretreatment suggests that this combination may have some wider perhaps clinical, potential.

Aclarubicin↗

PubMed1989

4'-O-tetrahydropyranyl adriamycin (THP-ADM)-induced modifications of murine peritoneal macrophages.

4'-O-tetrahydropyranyl adriamycin (THP-ADM) is a newly synthetized anthracyclin reported to be an efficient oncostatic drug in animals and in humans and which is less cardiotoxic than adriamycin (ADM). Since part of the efficiency of anthracyclins may be due to their immunoregulatory activity, we investigated to what extent THP-ADM had such properties and we observed that THP-ADM stimulates free oxygen radical secretion by murine peritoneal macrophages. They could thus help the control of infections cancer patients have a tendency to develop. Peritoneal macrophages of THP-ADM-treated mice have an in vitro cytostatic activity towards P815 tumor cells higher than normal cells and when stimulated with LPS they secrete more IL-1, an important effector of the immune response.

Animals↗

PubMed1988

Enhanced activity of murine peritoneal cells after aclacinomycin injection: characteristics of the enhanced respiratory burst.

After the i.p. injection into normal mice, of 4 mg/kg of aclacinomycin (ACM), a dose which prolongs the survival of tumor-bearing mice, the zymosan-elicited chemoluminescence (CL) of the peritoneal cells (PC) is greater than that of control cells. The volume in which the drug is administered plays an important role in the intensity of the response. ACM also stimulated the CL of PC from tumor-bearing mice. It is known that CL can also be elicited by soluble stimuli such as 4 beta-phorbol-12-myristate-13 alpha-acetate or Ca2+ ionophore A 23187, which, however, act in different ways. The response of ACM cells to these stimuli is also greater than in control cells. The enhanced CL of ACM-treated cells can be inhibited by incubating in vitro the zymosan-triggered PC with superoxide dismutase (300 units/ml) and catalase (2750 units/ml), but not with ethanol (20 microM) or potassium cyanide (100 microM). This indicates the participation of O2- and H2O2 in the CL of ACM-treated cells, whereas mitochondrial respiration does not appear to be involved. Furthermore, the following facts suggest the participation of arachidonic acid metabolism in the control of CL: (a) the in vitro addition of nordihydroguaiaretic acid (7 x 10(-6) M) and indomethacin (10(-3) M) inhibits the CL, while indomethacin (10(-6) M) has the opposite effect; (b) the PC from normal or ACM-treated mice when stimulated with zymosan secrete high amounts of prostaglandin (PG); (c) treated cells secrete the same amounts of PGE2 and 6-keto-PGF1 alpha but the secretion of PGF2 alpha and particularly of thromboxane B2 is greater in treated cells than in control cells and indomethacin (10(-6) M) strongly inhibits PG secretion in all groups; (d) in vitro addition of PGE2 at a concentration of 10(-6) M has an inhibitory effect on the CL emission of control and of treated cells, but it does not have this effect at lower concentrations (10(-8) M). These data suggest that the lipoxygenase pathway of arachidonic acid metabolism may be involved in the triggering of CL of ACM-treated cells, as well as that of normal cells, whereas products of the cyclooxygenase pathway may act as feedback inhibitors.

Aclarubicin↗

PubMed1988

Specific resistance to local graft-versus-host reaction in F1 hybrids pretreated intravenously with parent-strain spleen cells. Role of cytotoxic T lymphocytes directed against receptors for the major histocompatibility complex.

Pretreatment of B6D2F1 hybrids by injection of B6 spleen cells by subcutaneous or intravenous routes induces specific resistance to the local graft versus host reaction provoked by s.c. engraftment of B6 spleen cells. This resistance has been attributed to the presence in the pretreated F1 hybrids of cytotoxic T lymphocytes directed against receptors that recognize the D2 alloantigens (anti-D2-receptor CTL). However, this hypothesis would seem to be challenged, at least partially, by our previously published results showing that a) when tested before induction of GVHR, the anti-D2-receptor CTL are detectable in F1 hybrids pretreated only by the s.c. route but not by the i.v. route; and b) specific resistance to GVHR observed in i.v.-pretreated F1 hybrids is mediated by a nylon-adherent, Thy-1-, radioresistant (2000 rads) suppressor cell of B6 origin that does not manifest any anti-D2-receptor CTL activity. However, these results did not allow us to exclude the possibility of the presence, in the i.v.-pretreated F1 hybrids, of anti-D2-receptor precursor CTL that could be reactivated during the GVHR by the D2-receptors expressed on the proliferating clone of grafted B6 cells, then differentiate to the receptor-specific CTL effectors that control the development of the GVHR. That is why we have studied in the present work the CTL activity developed against D2-receptors after induction of GVHR in either normal or resistant F1 hybrids. Our results show that F1 hybrids protected against GVHR by i.v. pretreatment with B6 cells or by a transfer of nylon-adherent spleen cells from i.v.-pretreated syngeneic F1 mice do not manifest enhanced anti-D2-receptor CTL activity. When considered along with our previous observations, these results favor our hypothesis that anti-D2-receptor CTL are not involved in the specific resistance to GVHR observed in the i.v.-pretreated F1 hybrids.

Animals↗

PubMed1987

Enhanced activity of mouse peritoneal cells after aclacinomycin administration.

We have investigated the activation of mouse peritoneal macrophages by injection of aclacinomycin (ACM). Macrophages from ACM-treated mice have an increased phagocytic activity as measured by Candida ingestion. The microbicidal activity indirectly evaluated by chemiluminescence and superoxide determination in response to stimulation with zymosan and 4 beta-phorbol-12-myristate-13 alpha-acetate is also greater in the cells from treated mice. Direct measurement of the cytostatic function, and of in vitro and in vivo cytotoxicity shows comparable significant increases against L1210 or P815 target cells. The enhanced antitumoral activity could not be attributed to the residual presence of ACM in the peritoneal cells since no drug was detected by high-performance liquid chromatography and since their freeze-thaw lysates incubated with P815 cells did not modify the growth of tumor cells as measured by [3H]-thymidine incorporation. We also checked that the presence of ACM did not influence the intensity of the chemiluminescence. In all tests performed, only i.p. ACM administration could stimulate the peritoneal cells. Since the doses of ACM inducing an increase in macrophage activity are effective on the survival of tumor-bearing mice, the participation of this mechanism in tumor control might be suggested.

Aclarubicin↗

PubMed1987

Anti-receptor anti-MHC cytotoxic T lymphocytes: their role in the resistance to graft vs host reaction.

Specific resistance to local graft vs host reaction (GvHR) observed in F1 hybrids pretreated s.c., i.p., or i.v. with parent strain spleen cells has been explained as being due to cytotoxic cells induced in these pretreated F1 hybrids and directed against cells bearing receptors that recognize the major histocompatibility complex (MHC) alloantigens of the opposite parent strain (anti-receptor anti-MHC cytotoxic T lymphocytes; CTL). These anti-receptor anti-MHC CTL, however, have never been detected directly in popliteal lymph nodes (PLN), which develop a specific resistance to GvHR. In this paper, we describe the detection of anti-receptor anti-D2 cytotoxic activity in both right and left PLN of B6D2F1 hybrids injected s.c. in the right footpad only with B6 spleen cells. This cytotoxic activity appears 4 days after the injection of B6 cells and diminishes by day 7. It is mediated by a Thy-1+, L3T4-, Lyt-2+ cell of B6D2F1 origin and induced by the injection of either Thy-1+L3T4+Lyt-2- or Thy-1+L3T4-Lyt-2+ B6 spleen cells. The anti-receptor anti-D2 CTL activity is not observed in PLN of B6D2F1 hybrids pretreated i.p. or i.v. with B6 spleen cells. Our results demonstrate that anti-receptor anti-MHC CTL can fully explain the specific resistance to GvHR induced by the s.c. pretreatment of F1 hybrids with parent strain spleen cells. Their role, however, in the resistance to GvHR observed in F1 hybrids i.v. or i.p. pretreated is far from being entirely proven.

Animals↗

PubMed1987

Specific inhibition of hybrid resistance in F1 hybrid mice pretreated with parent strain spleen cells. I. Induction of a nylon-adherent, Thy-1+Lyt-1+2- suppressor cell.

Hybrid resistance, which is observed in certain strain combinations when parent-strain bone marrow cells are grafted into lethally irradiated F1 hybrids, can be specifically overcome by the i.v. injection, 1 wk before the graft, of spleen cells syngeneic with the bone marrow graft. This phenomenon is due to a suppressor mechanism, induced in the spleen of the F1 hybrid by the injection of parent-strain spleen cells and mediated by a nylon-adherent Thy-1+Lyt-1+2- cell population of hybrid origin, because hybrid resistance can be inhibited by the transfer into a normal B6D2F1 of nylon-adherent Thy-1+Lyt-1+2- spleen cells from B6D2F1 mice pretreated with B6 spleen cells 1 wk earlier (B6-pretreated B6D2F1); spleen cells from B6-pretreated B6D2F1 mice not depleted of their nylon-adherent subpopulation cannot restore hybrid resistance when they are injected into a B6D2F1 rendered nonresistant by split-dose irradiation; and spleen cells from normal B6D2F1 mice cannot restore hybrid resistance when they are injected into B6-pretreated B6D2F1 hybrids. The suppressor cells specifically inhibit resistance against bone marrow cells syngeneic with the spleen cells used for pretreatment, because transfer of nylon-adherent B6-pretreated B6D2F1 spleen cells into a normal B6D2F1 does not enhance syngeneic B6D2F1 or parent-strain D2 bone marrow growth, and when injected into normal B6D2F1 hybrids, nylon-adherent spleen cells from B6D2F1 mice pretreated with D2 spleen cells 1 wk earlier (D2-pretreated B6D2F1) are not able to transfer the inhibition of hybrid resistance against B6 bone marrow cells. Moreover, the activity of the suppressor cells depends on the genetic environment of the hybrid host mice, because nylon-adherent B6-pretreated B6D2F1 spleen cells injected into normal B6C3F1 hybrids do not transfer an inhibition of hybrid resistance, and when injected into B6C3F1 hosts previously rendered nonresistant by split-dose irradiation, spleen cells from B6-pretreated B6D2F1 mice can, in contrast, transfer hybrid resistance.

Animals↗