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

The in vitro clonogenic survival of human fibroblasts with a genetically defined glutathione (GSH) deficiency was studied after irradiation with X-rays in oxygen or in oxygen free argon. Genetically related fibroblasts without GSH deficiency were used as a control. The oxic survival curve of both cell lines was similar. In comparison to the oxic survival curve, the anoxic survival curve of GSH deficient cells indicated an oxygen enhancement ratio (OER) approximately 1.5. An OER approximately 2.9 was calculated in comparing the oxic and anoxic survival curves of the control cell line. The results were discussed in support of the theory according to which oxygen and GSH compete for radiation induced radicals in key molecules, the former irreversibly fixing and the latter repairing the radiation damage.

Liver scanning with 99mCi 99Tc sulphur-colloid was practiced in 50 patients: 30 suffering from malignant tumors, 10 from hepatic cirrhosis and 10 from pyrexia of unknown origin. Liver radioactivity was recorded by a gamma-camera connected to a computer, 1 frame each 10 seconds for 15 minutes. The spectral analysis of the radioactivity counts taken in different region of interest, showed evidence of a periodic fluctuation, with a period value around 1 minute. Comparative ultrasonographic dynamic study showed evidence of the same phenomena in 16 examined patients. The period of pulsation was found different in each of the following groups: normal liver, cirrhotic, metastatic and infectious diseases.

The influence of six antitumor drugs of natural origin (rubomycin, bruneomycin, olivomycin, mitomycin C, vinblastine, and vincristine) on five transplantable tumor models (sarcoma 37, sarcoma 180, Ehrlich tumor, RL-67 and TAVS) was investigated. Each tumor was transplanted subcutaneously and intramuscularly, bilaterally, on one animal. Marked differences in the sensitivity between subcutaneous and intramuscular form of Ehrlich tumor and more slightly of TAVS were established. The used experimental regimen held out possibilities for saving labor, animals and substances as well as for the study of potential antitumor substances of natural origin at maximum equalized biological conditions.

Myosin was isolated from heart ventricle, soleus and gastrocnemius of freshly slaughtered swine. ATPase activities (mu moles Pi/mg/min) were found to be higher in heart muscle (Ca++ activated = .39 +/- .04; EDTA activated = .59 +/- .06) than in ST soleus (Ca++ activated = .23 +/- .02; EDTA activated = .48 +/- .05) or FT gastrocnemius (Ca++ activated = .32 +/- .03; EDTA activated = .52 +/- .04). The results suggest that the myosin of swine cardiac muscle is different from the myosin of skeletal muscle, or at least, the rate of hydrolysis of ATP on the myosin sites is different between these tissues. There is a difference in relationship of ATPase between heart and skeletal muscle in swine compared to that seen in other mammalian species.

Long-term hemopoiesis was established in bone marrow cell culture in vitro. This culture was shown to support the recovery proliferation of hemopoietic stem cells completely in vitro after irradiation. Hemopoietic stem cells were stimulated into proliferation in culture when normal bone marrow cells were overlayed on top of the irradiated adherent cell colonies. These results indicate that proliferation and differentiation of hemopoietic stem cells in vitro are also supported by stroma-hemopoietic cell interactions.

Colonies were obtained from peripheral blood lymphocytes (PBL) grown in soft agar in the presence of PHAM or PHAp mitogens. One out of 130 PBL was able to generate a colony. Colony cells were mass harvested and assayed for surface markers and cytotoxic potential. Most of the colony cells (83%) form spontaneous rosettes with sheep-red blood cells (RBC) and bear the human T lymphocyte antigens (HTLA) (92%). A significant amount of colony cells able to bind autologous RBC was detected (24%). The capacity of PBL and colony cells to bind Ox-RBC sensitized with rabbit anti-Ox-RBC IgM (EAM complexes) was measured: only 15% of colony cells compared to 49% of the PBL formed EAM rosettes. The capacity of cells to bind the Fc portion of antigen-complexed IgG was investigated by two rosette assays: using Chicken or Ox-RBC sensitized with a rabbit anti-Chicken-RBC or Ox-RBC IgG (Chicken EAG or Ox-EAG complexes). The percentage of colony cells forming Chicken EAG rosettes was low (3.6%) compared to PBL (12%). This percentage was significantly increased with PHAp, and not PHAM stimulation (11%). Using Ox-EAG complexes, we confirmed the low percentage of EAG rosettes in colony cells under PHAM stimulation (4.7%) compared to PBL (21%). A significant cytotoxic capacity (spontaneous or antibody dependent) was found in colony cells after PHAM stimulation. This method of culture is able to generate clones of T cells and conserve T cell subsets and cytotoxic potential usually found in a T purified population. In further studies, it will be interesting to investigate if each clone possesses specific markers and cytotoxic potential and is able to maintain this differentiation step in long term culture.

The anti-leukemic effectiveness (GvL activity) and anti-host response (GvH response) of several allogeneic donor marrows were compared in lethally irradiated normal and Rauscher leukemia SJL/J recipients. Although both types of effects could be demonstrated, the degree of GvL activity did not parallel the severity of GvH response. The level of GvL activity of the donor marrow also appeared to be independent of sensitivity of the donors to the leukemia inducing Rauscher virus (RLV), as a high level of leukemia recurrence was found using marrow from RLV-resistant RF/J donors, while a lesser degree of recurrence occurred with the use of RLV-sensitive DBA-2J marrow. Analysis of the possible influence of major (MHC) and Minor (MiHL) histocompatibility loci suggested that GvL activity may be independent of the H-2 locus, and that the "a" alleles of the H-4 and H-13 loci may not be contributing to GvL effect. Likewise the "a" alleles of the H-7 and H-12 loci did not appear to affect the severity of GvH response. The possibly that GvL activity may be independent of th MHC, but governed by MiHL possibility different from those regulating GvH response might explain why in this and previous studies GvL activity could only be demonstrated following allogeneic marrow transplantation but did not appear to correlate with severity of GvH response.

Enhanced nucleocytoplasmic RNA transport has been demonstrated by incubating normal rat liver nuclei in presence of cytosols originating from the poorly differentiated, fast-growing hepatoma HW-165, in the linear phase of tumor growth. The effect of hepatoma HW-165 cytosol was reduced or suppressed in presence of small amounts of normal liver cytosol: on the other hand, several polypeptides of molecular weight 20,000 to 40,000 daltons were hardly detectable in hepatoma HW-165 cytosol, both arguments indicating that potentially regulatory proteins should be absent or present in reduced concentration in hepatoma HW-165 cytosol. No modification of RNA release was observed in presence of cytosols originating from the thymus of RNA virus (BL/F)-infected rats, whatever be the time after inoculation. Attempts were made to use the nuclear restriction assay, supplemented with plasma or serum of various origins, as a biochemical marker of neoplasia. In a first series of assays, including 80 cancer patients and 12 healthy controls, the RNA transport activity was stimulated by the serum of patients bearing various tumors (lung cancer, cancer of the respiratory tract, uterine cervix...), except in a few cases of mammary carcinoma, where values equivalent to or lower than the controls were obtained.