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

The effect of propranolol (non specific blocking agent), acebutolol (beta 1 blocking agent), butoxamine (beta 2 blocking agent) and several beta adrenergic agonists was studied on 3H-thymidine (3H-TdR) incorporation and granulo-monocyte colony formation in agar by human bone marrow. Only butoxamine and propranolol decreased 3H-TdR incorporation by total normal bone marrow cells at concentrations above 10(-6) M for butoxamine and 10(-5) M for propranolol. Autoradiography showed that inhibition of 3H-TdR incorporation by butoxamine was slightly more pronounced on neutrophil precursors than on red cell precursors (neutrophil series LI..53 and erythroblasts .67 compared to control bone marrow cells at 10(-5) M concentration). The development of granulo-monocyte colonies in agar culture was delayed by preincubation with butoxamine at concentrations above 5 X 10(-6) M. Hydroxyurea suicide showed that this was due to a decrease in the number of CFU-C in S phase. beta 2 blocking agents are able to decrease the number of normal hematopoietic cells entering S phase. This effect is seen on both neutrophil and erythroblastic precursors and on granulo-monocyte progenitors. It could be used as a means of protecting bone marrow cells during cancer intensive chemotherapy.

Acute glucose loading studies were performed on seven diabetic patients and 18 control subjects. In two normaldosteronemic insulin-dependent diabetic patients during high sodium intake and insulin withdrawal infusion of hypertonic glucose induced a paradoxical elevation of serum potassium levels, while no such abnormalities were found in two other diabetics despite of lower plasma aldosterone levels. Paradoxical glucose-induced hyperkalemia (PGIH) was abolished during insulin withdrawal by sodium restriction associated with a dramatic increase in plasma aldosterone. PGIH was elicited when given 100 g of glucose orally to further three patients with normaldosteronemic diabetes in whom a complete reversal of PGIH was obtained l glucose-induced hyperkalemia (PGIH) was abolished during insulin withdrawal by sodium restriction associated with a dramatic increase in plasma aldosterone. PGIH was elicited when given 100 g of glucose orally to further three patients with normaldosteronemic diabetes in whom a complete reversal of PGIH was obtained l glucose-induced hyperkalemia (PGIH) was abolished during insulin withdrawal by sodium restriction associated with a dramatic increase in plasma aldosterone. PGIH was elicited when given 100 g of glucose orally to further three patients with normaldosteronemic diabetes in whom a complete reversal of PGIH was obtained also by sodium restriction or by administering a large intravenous dose of desoxycorticosterone. These findings suggested an elevated mineralocorticoid threshold level for the normal cellular regulation of potassium distribution in normaldosteronemic diabetics with PGIH.

The synthesizing activity and ultrastructural appearance of human polymorphonuclears, lymphocytes and platelets obtained from healthy donors were examined after incubation with cis-platinum (cis-Pt). The drug caused a statistically significant inhibition of DNA, RNA and protein synthesis of the lymphocytes, but their ultrastructure appeared unchanged. On the other hand, incubation of polymorphonuclears with cis-Pt did not affect their protein synthesis but caused a decrease in the number of cytoplasmic granules, mitochondrial alterations, and appearance of membrane ruffles. The drug induced neither inhibition of platelet protein synthesis, nor ultrastructural alterations. The selective effect of this drug on the synthesizing activities of human lymphocytes may be of potential value in the treatment of lymphoproliferative and immunological disorders in man.

The distribution of fibroblastic colony forming units (CFU-F) in mouse femoral marrow was investigated using a method which separates bone marrow cells into two regional fractions of varying size. It is shown that the concentration of CFU-F decreases almost linearly from the femoral axis (800-1,000 CFU-F per 10(7) bone marrow cells) to the bone surface (300 CFU-F per 10(7) cells). When irradiated axial or marginal cells were added into cultures as feeder cells, the colony numbers produced by both axial or marginal CFU-F were increased by about 50% and the higher concentration in the axial regions remained. The survival curve for CFU-F in both regions was characterised by a Do value of 1.54 +/- 0.11 Gy and an extrapolation number of 2.60 +/- 0.38. The results are compared to the distributions of haemopoietic stem cells and committed progenitor cells.

An attempt was made to reproduce the in vivo situation of the hemopoiesis in genetically anemic mice in vitro. Cultures of the bone marrow cells from W/Wu, Sl/Sld and control (+/+) mice revealed that all of the hemopoietic stem cells in these mice could be maintained in vitro as well. Similar results were also obtained with the spleen cell cultures. Since these anemic mice have near normal levels of committed progenitor cells, and pluripotent stem cells in Sl/Sld mice, and a subnormal level of functional blood cells sufficient for the survival of the mice, there should be a slow and constant hemopoiesis, under normal conditions. Such a slow but steady production of hemopoietic cells appears to be well reproduced in vitro.

Interferon production and lymphocyte transformation were obtained in human lymphocytes from different donors, in response to Chlamydia trachomatis. Two interferon peaks were observed respectively on the 2nd and 5th days after infection. The early peak contains principally alpha-interferon, while the late peak is a mixture of alpha and mostly gamma-interferon.

We have investigated the mechanism of glucan-mediated increase of splenic (SPL) and decrease of bone marrow (BM) hemopoiesis in B6DF1 mice. To determine the involvement of macrophages in these phenomena, B6DF1 mice were treated with silica 24 hrs prior to glucan injection and then tested for BM and SPL CFU-GM and CFU-S activities. Silica treatment reduced significantly augmentation of SPL, but not the decrease of BM CFU-GM proliferation, indicating that the former phenomenon is macrophage dependent, whereas the latter is not. Since no change in BM or SPL CFU-S proliferation was observed after silica treatment, it appears that macrophages are not involved in glucan-caused alterations of CFU-S. Athymic mice (not possessing mature T cell functions) also exhibited decreased BM and increased SPL CFU-GM proliferation after glucan treatment; however, the SPL CFU-GM augmentation in athymic mice was not as dramatic. Hence, although glucan's action did not appear to be completely dependent on mature T-cells, these cells appear in some way to act with macrophages to enhance the proliferation of SPL CFU-GM after glucan treatment.

The carbohydrate composition of 18 monoclonal IgM (Waldenström macroglobulinemia) was determined by gas-liquid chromatography. Two populations occurred with mean sugar contents of 7.3% (12 IgM and 10% (6 IgM). A value of 7.2% was obtained for 8 IgM prepared from 8 normal sera. On the basis of mean molar ratios established for each monosaccharide residue, structural models for oligosaccharide units are proposed. The number of complex glycan chains (N-acetyllactosaminic type) is higher in the 10% population, which would correspond to IgM with a mean sedimentation constant of 18.3So20, W. On the other hand, the 7.3% population has a lower content of "mature" chains and its sedimentation constant would be inferior: 17S)20, W.

Phosphodiesterases from blood cells and serum can be subdivided in several groups according to substrate specificity, optimum pH and effects of inhibitors: 1) Acidic phosphodiesterase activities were not inhibited by EDTA, represented the whole p3'T hydrolysing activity, but only a part of the activity hydrolysing the other substrates (p5'T was not hydrolysed at acidic pH). This acid phosphodiesterase activity was high in white blood cells and platelets but very low in serum. 2) Neutral phosphodiesterase activity was prevalent in leucocytes when BpP and BMP were used as substrates. 3) Alkaline phosphodiesterase activity was characterized by substrate specificity at optimum pH and distribution in cells and serum: in serum there are phosphodiesterases hydrolysing all checked substrates (p3'T excepted) at optimum pH 9.0, whereas in blood cells alkaline phosphodiesterase activities are very low for all substrates (excepted for p Phi Pn and p5'T). In each cell and serum we have determined, for all phosphodiesterase activities, the linearity of activity of versus time and versus protein concentration, the effect of substrate and effector concentration and the heat stability.