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Biomedical subjects

H Bessler

Publications and source records attributed to H Bessler.

At least 19 recordsLinked to original sources

Immunomodulatory effect of peripheral benzodiazepine receptor ligands on human mononuclear cells.

Immunomodulatory effect of ligands active at the peripheral benzodiazepine receptor (PBR) was examined in human peripheral blood mononuclear cells (PBMC). Ro5-4864, PK11195 and diazepam suppressed phytohemagglutinin (PHA) and concanavalin A (ConA) induced proliferation of PBMC. All three ligands inhibited interleukin-3-like activity (IL-3-LA) secretion, while the production of interleukin-2 (IL-2) was inhibited by Ro5-4864 and diazepam only. The selective central benzodiazepine ligand clonazepam did not affect the cellular immune functions examined. Our results indicate an in-vitro immuno-suppressive activity of peripheral and mixed, but not central type benzodiazepine ligands.

Adjuvants, Immunologic

SEM observations on the mechanism of platelet release from megakaryocytes.

Normal human bone marrow megakaryocytes were examined with the scanning electron microscope (SEM) to clarify the mechanism of platelet release. Several types of megakaryocytes were dtected according to their surface appearance, i.e. with wrinkles, ridges, villous formations, round blebs and cells with platelets still attached to the cell membrane. These observations are consistent with the concept that bleb formation is at least one of the mechanisms for platelet liberation.

Blood Platelets

pH-induced platelet ultrastructural alterations. A possible mechanism for impaired platelet aggregation.

After the observation that lavages with alkaline solutions exert a beneficial effect on the bleeding tendency and increase platelet aggregation in patients with intragastric hemorrhage, studies were undertaken to find a relationship between changes of pH and platelet morphology. Transmission and scanning electron microscopy showed that at a pH lower than 7.4, normal human platelets change their internal structure as well as their shape, becoming spheres deprived of pseudopodia. On the other hand, a pH higher than 7.4 induces transformation of platelet internal organelles similar to that caused by thrombin. At an alkaline pH, the platelets develop multiple pseudopodia that facilitate their attachment to each other. These findings may explain the increased platelet aggregation in alkaline medium demonstrated in one of our previous works.

Blood Platelets

The surface ultrastructure of Gaucher cells.

The Gaucher cells of seven patients with Gaucher's disease were examined by both transmission and scanning electron microscopy. The ultrastructure of the cells, as seen by transmission electron microscopy, did not differ from that reported in the literature. The surface structure varied not only in the different patients but also in the same individual. The cells were oval or round, most of them with a rough surface due to presence of microvilli, ruffles, ridges, and blebs of various numbers and shapes. In two patients the Gaucher cells showed phagocytosis. The appearance of the surface ultrastructure of the Gaucher cells supports the accepted view that they are related to the cells of the reticuloendothelial system.

Adolescent

Increased RNA and heme synthesis in mouse erythroid precursors by parathyroid hormone.

The in vitro effect of parathyroid hormone (PTH) on RNA and heme synthesis by embryonic mouse liver erythroid precursors was examined. PTH produced a dose-dependent effect on RNA synthesis. A maximal increase of 60 +/- 16% (p less than 0.02) was observed with 1.0 U PTH/ml, whereas with higher concentrations a significant decline was found. Furthermore, PTH stimulated heme synthesis after 24 h of incubation. The maximal enhancement of 32 +/- 7% (p less than 0.01) was observed with 0.5 U PTH/ml, a lower effect was obtained with 1.0 U PTH/ml, while 2.0 U PTH/ml caused a pronounced decrease of heme synthesis. These data indicate that PTH affects directly the erythroid precursors by a mechanism similar to that of erythropoietin. The inhibitory effect on the RNA synthesis observed with large doses of PTH may explain at least one of the causes of the anemia reported in patients with primary hyperparathyroidism.

Animals

The role of hemin in the regulation of heme synthesis by fetal mouse liver erythroblasts in culture.

The regulatory role of exogenous hemin on the heme synthetic pathway was studied in fetal mouse liver erythroblasts in culture. Hemin added to culture medium of 13th day embryo liver cells inhibited, dose dependently, the incorporation of the porphyrin precursors, 59Fe, 14C-2-glycine and 14C-5-aminolevulinic acid (ALA) by 85%, 70% and 45%, respectively. This suggests a multiple effect of hemin on the porphyrin biosynthetic enzymes. Exogenous ALA competed with 14 C-2-glycine as a porphyrin precursor, but the rate of heme synthesis, measured by 59Fe incorporation, remained unaltered. Protoporphyrin mimicked the hemin effect on the inhibition of glycine incorporation into heme, but reduced iron incorporation by only 20%. Erythroblasts, with an inhibited porphyrin biosynthesis, utilized exogenous 59Fe-hemin for hemoglobin assembly and maintained an undecreased level of hemoglobin synthesis. The results indicate that hemin inhibits the porphyrin biosynthesis in fetal mouse liver erythroblasts mainly at the iron incorporation stage.

Aminolevulinic Acid

Effect of prostaglandin A2 on RNA synthesis in embrionic mouse erythroid cells.

Prostaglandin A2 (PGA2) is shown to stimulate RNA synthesis in 12-day embryonic mouse liver cells, thus expressing an erythropoietin-like effect. This effect was found to be dose-dependent. There was no significant difference between the results observed with patients' plasma before and after dialysis and with or without addition of PGA2. Although the baseline activity of RNA synthesis in the presence of uremic plasma is less than that with normal plasma, the almost equal potentiation of RNA synthesis in erythroid cells incubated with both normal and uremic plasma obtained with PGA2 favors a direct, and not an erythropoietin-mediated, effect of this substance.

Animals

SEM observations on Sendai virus-induced fusion of embryonic mouse erythroblasts.

The events of fusion of 11- and 16-day embryonic mouse liver erythroblasts induced by Sendai virus (SV) were followed with the scanning electron microscope (SEM). Erythroid precursors incubated with the virus showed numerous 'pores' on the cell membrane. The cell fusion began with the appearance of a fine 'meshwork' structure between the adjacent cells, followed by a gradual formation of a common cell membrane and terminated with the appearance of polykaryons, in which the nuclei were easily recognized when located in the vicinity of the polykaryon membrane. There was no difference in the process of fusion between erythroblasts at identical and those at different stages of maturation.

Animals

Role of the spleen and lymphocytes in regulation of the circulating platelet number in mice.

The role of the spleen in the regulation of the circulating platelet number was studied in mice. The increased 75Se-Met incorporation found after removal of the spleen indicates that postsplenectomy thrombocytosis is due to enhanced platelet production. The increased thrombopoietic activity observed in the plasma of splenectomized mice proves the presence of a humoral factor which mediates this process. Administration of spleen lymphocytes to control mice caused mild thrombocytopenia and prevented postsplenectomy thrombocytosis in splenectomized animals. Moreover, culture medium obtained from peripheral blood and spleen lymphocytes contained a substance which induces thrombocytopenia when injected into control mice. The mechanism by which the spleen and lymphocytes affect the amount of circulating platelets is discussed.

Animals

Erythroid precursor fusion induced by Sendai virus.

The ultrastructural events of the interaction of Sendai virus (SV) with fetal mouse erythroid precursors, and SV-induced fusion of erythroid precursors at different maturation stages are described. SV was shown to affect the erythroid nuclei causing interruption of the nuclear membrane, enlargement of the nucleolus and nuclear fusion. SV induced fusion also between dividing and non-dividing cells.

Animals

Effect of a low dose of vincristine on platelet production in mice.

The effect of a single low dose (0.1 mg/kg) of vincristine (VCR) on platelet production was investigated in C57B1 mice. A parallel increase of circulating platelets and (75Se)-selenomethionine (Se-Met) uptake was observed. The total megakaryocyte count decreased insignificantly 6 hours after VCR injection, followed by an increase after 18 hours. Plasma taken from mice 24 hours after VCR injection was tested for thrombopoietic activity. The post-VCR plasma caused a significant thrombocytosis, increased Se-Met uptake and increased protein synthesis of the platelets, indicating an active overproduction of platelets. These results suggest that the thrombocytosis induced by a low dose of VCR is mediated by a thrombopoietin-like substance.

Animals

Increased protein synthesis by human platelets during phagocytosis of latex particles in vitro.

A three-fold increase of protein synthesis by human platelets during in vitro phagocytosis of polystyrene latex particles was detected. During the first two hours of incubation, the percentage of phagocytizing platelets and the number of latex particles per platelet increased; by the end of the third hour, the first parameter remained stable, while the number of latex particles per cell had decreased. Vincristine (20 mug/ml of cell suspension) inhibited platelet protein synthesis. This effect was both time- and dose-dependent. The drug also caused a decrease in the number of phagocytizing cells, as well as in their phagocytotic activity.

Blood Platelets

In vitro DNA and RNA synthesis by human platelets.

In vitro incorporation of [Me-3H] thymidine and [5-3H] uridine into human platelets was demonstrated. Thymidine incorporation was inhibited by three specific inhibitors of DNA synthesis: hydroxyurea, cytosine arabinoside and daunomycin. The effect was dose-dependent. Uridine uptake by platelets was found to be inhibited by specific inhibitors of RNA synthesis such as actinomycin D, rifampicin and vincristine, the effect of actinomycin D being dose dependent. The drug also led to a time-dependent inhibition of protein synthesis when preincubated with platelets. The platelet RNA profile on polyacrylamide gel was demonstrated to be similar to that of embryonic mouse erythroblast RNA. Synthesis of all three fractions, 28 S, 18 S and 4 S, was inhibited by actinomycin D. These findings show that human platelets are capable of DNA and RNA synthesis, and that these activities play a role in controlling protein synthesis in these cells. Detectable amounts of DNA have been found in whole human platelets, and in isolated mitochondria derived from these cells. Isolated platelet mitochondria incorporated [3H] thymidine and [3H] uridine into their macromolecules. These activities were inhibited by daunomycin and by both rifampicin and actinomycin D, respectively. These results support the assumption that DNA and RNA synthesis found in intact cell preparations takes place most probably in platelet mitochondria.

Blood Platelets

Chloramphenicol induced inhibition of platelet protein synthesis: in vitro and in vivo studies.

Chloramphenicol (CAP), an antibiotic which causes various blood dyscrasias, was shown to inhibit in vitro protein synthesis of human blood platelets. The effect is dose- and time-dependent, it is reversible after incubation for 2 h, and is comparable with the suppression achieved by cycloheximide (CXM). Electron microscopic examination revealed swelling and destruction of mitochondria. Administration of CAP to dogs produced a progressive inhibition of platelet protein synthesis as shown by a reduction in the rate of [3H]leucine incorporation into protein. The maximal inhibitory effect of the antibiotic was reached 0.5-4.0 h after its administration, when minimal leucine incorporation values of 9-40% of the control were measured. The suppressive effect of CAP was followed by an overshoot in the incorporation of [3H]leucine, up to a maximum of 602% of the value at zero time of the experiment.

Animals

Erythropoietic events in cultured embryonic mouse spleen.

The events of erythropoiesis in cultured embryonic mouse spleens isolated on the 12th day of gestation were compared with those occurring in spleens of corresponding gestational days in vivo. It was found that the development of erythroid precursors in the cultured spleen depended on the presence of erythropoietin in the culture medium. A progressive increase in the number of erythroid precursors, with a marked shift to mature cells, was observed in spleens cultured with erythropoietin. Although the origin of the hemocytoblasts in the spleen isolated in the earliest stage of its development remains obscure, the present study provided evidence that erythropoiesis in the embryonic mouse spleen was indigenous to this organ and did not result from colonization of erythroid precursors originating in the liver.

Animals