Biomedicine / [publiee pour l'A.A.I.C.I.G.]最新文献

It has been suggested that lipid peroxidation is an important factor in the pathogenesis of carbon tetrachloride (CCl4) hepatotoxicity. In the present study, experimental liver injury induced by CCl4 could be prevented by levamisole, an antihelminthic agent and immunomodulator. Despite of exposure to CCl4 tissue levels of thiobarbituric acid (TBA) reacting substances in the liver were not increased in rats pretreated with levamisole. On the other hand, when we administered levamisole, 150 mg p. o. daily given on three consecutive days of each week, to six elderly patients with arteriosclerosis. They all showed a significant decrease in serum TBA reactive substances during the 12 weeks of therapy. This provides evidence that levamisole prevents liver damage by CCl4, and indicate the possibility that levamisole might have an antioxidative effect or may prevent the accumulation of TBA reactive substances.

The mechanism of action of burst-promoting activity (BPA) was investigated. Rabbit bone marrow conditioned medium (BMCM) was used as a source of BPA for bone marrow derived rabbit erythroid progenitors (BFU-e). The addition of 10% BMCM to methylcellulose cultures resulted in an increase in both burst number (60%) and 59Fe incorporation into heme (1,334%). A strong correlation was observed between cell number and 59 Fe incorporation individual bursts. Analysis of cell number in individual bursts cultured in the presence or absence of BMCM demonstrated that BMCM consistently enhanced burst size. When bone marrow cells were incubated for 4 hours in BMCM prior to culture, a three fold increases in the percentage of S-phase BFU-e was observed. These results show that a major mechanism of action of BMCM burst-promoting activity is to enhance proliferation during the early phase of burst formation.

Sixty-six patients with chronic myelogenous leukemia, all with Philadelphia chromosome, have been studied for chromosomic abnormalities associated (CAA) to Ph', as well as for actuarial curve of survivorship. Patients dying from another disease were excluded from this study. Frequency of cells with CAA was measured and appeared strongly higher after blastic transformation than during myelocytic state; probability to be a blastic transformation is closely correlated with this frequency. On the other hand, actuarial curve of survivorship is very well represented by an exponential curve. This suggests a constant rate of death during disease evolution, for these patients without intercurrent disease. As a mean survivance after blastic transformation is very shorter than myelocytic duration, a constant rate of blastic transformation could be advanced: it explains possible occurrence of transformation as soon as preclinic state of a chronic myelogenous leukemia. Even if CAA frequency increases after blastic transformation, CAA can occur a long time before it and do not explain it: submicroscopic origin should be searched for the constant rate of blastic transformation would express the risk of a genic transformation at a constant rate during myelocytic state.

The effect of X-irradiation on growth of T-lymphocyte colony forming units (TL-CFU) from human peripheral blood was investigated. The results indicate that not the number of activated TL-CFU but the number of cell cycles of colony forming cells was reduced by X-irradiation. Therefore we presume that TL-CFU belong to a relatively radio-resistant cell population within the PHA-responsive lymphocytes. Kinetic studies revealed that colony growth following irradiation was delayed mainly during the phase of the first cell cycle. Preculture of the cells for 24 hours after irradiation with 1,200 R in the absence of PHA caused total inhibition of colony growth in the subsequent agar culture. In the presence of PHA no inhibition was observed. This finding appears to reflect a repair mechanism from radiation damage of lymphocytes stimulated by PHA.

Tricyclic antidepressants (imipramine and desipramine) gave rise to an important decrease of sphingomyelinase activity in murine neuroblastoma and human fibroblast cell cultures. It occurred within 1 to 2 hours at a final concentration of 1 or 2 X 10(-5) M in cell culture medium. Other lysosomal enzymes such as acid lipase, arylsulfatases A and B and hexosaminidases were not modified. Low level of sphingomyelinase activity may be related to the amphiphilic characteristics of the drugs: iminodibenzyle which has the same tricyclic core but is devoid of the side chain necessary for amphiphilic properties had no effect. As iminodibenzyle has no therapeutic action, amphiphilic may be requisite to antidepressant properties of tricyclic drugs.

The development of a fast-growing hepatoma (HW-165) in normal euthyroid Wistar rats, was shown to be stimulated by daily injection of a dose of triiodo-L-thyronine (T3) as low as 1.5 microgram/100 g body weight. Administered to thyroidectomized rats, T3 completely restored the frequency of tumor initiation and accelerated the growth of the hepatoma, which had been considerably slowed down in hypothyroid rats. Contrary to other investigators, working on fast-growing Morris hepatomas, we did not observe any significant increase in the T3 level in the serum of hepatoma HW-165-bearing rats. Similarly, the tetra-iodo-L-thyronine (T4) levels were of the same order of magnitude in the blood of both normal and tumor host animals. The mitotic activity was reduced in hepatomas transplanted in hypothyroid rats and increased in tumors of T3-treated animals. These results support the assertion of Short (20) suggesting a relationship between the mitogenic effects of iodothyronines on the normal hepatocyte and on transplanted tumors of hepatic origin.

A high level of antitumoral cytotoxicity was observed in the lymphoid population extracted by perfusion from lung capillaries. The in vitro cytotoxicity against tumor cells was demonstrated with the murine lymphoma YAC-1 cells or with the syngeneic P 77 rat lung fibrohistiocytoma cells. It was demonstrated that this cytotoxic activity had the characteristics of natural killer activity. At the same effector to target ratio the efficiency of this population was higher than in blood or spleen. Since the total number of lymphoid cells arrested in the capillary of the lungs is very high the lungs seemed an immunologically privileged site. A close relationship was observed between this activity in vitro and the rapid elimination in vivo of same tumor cells trapped in lungs (more than 99% after 24 hours).

The serological EBV profile of 2752 pregnant women characterized in most cases a latent EBV carrier state. The pregnancy rarely reactived this latent infection. But mothers with an "active" EBV serology gave birth more frequently than others to still born or defective bodies. In six pregnancies with primary EBV infection, detected early, four presented a pathological delivery. Furthermore the follow up of the EBV profile in 719 mothers revealed a significant relation between defective births and persistent EA antibodies. The role of EBV has yet to be precisely defined but the early detection of anti-EA EBV antibodies should be considered as a risk indicator in the management of pregnancy.

We have examined the reported role of suppressor cells in the regulation of NK activity in mice with naturally low NK activity (infant and aged (C57 X A)F1 hybrids (CAF1) and low responder strain AKR mice). Possible suppressor activity was assayed by mixing, at a 1 : 1 ratio, spleen cells from low activity mice with spleen effector cells from normally active 8 to 10 wk old CAF1 mice. The lytic activity of the mixture was compared with the activity of effector cells diluted with medium alone or diluted 1 : 1 with "non-suppressor" population which served as a control for nonspecific decreases in lysis. The control or "filler" cells employed were suspensions of adult CAF1 thymus, thymus from adult mice exposed to 2,000 R, and adult CAF1 spleen cells cultured for 24 hours, a procedure that depleted NK activity. In no case was the activity observed in the presumed suppressor-effector mixture significantly lower than that observed in the filler-effector cell mixtures. Thus, in infant (1 to 2 wk) and aged (12 to 18 mo) CAF1 mice and in 8 to 10 wk old AKR mice, we found no evidence for specific cell-mediated suppression of natural cytotoxicity.