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Biomedical subjects

A S Gordon

Publications and source records attributed to A S Gordon.

At least 145 records · Page 8Linked to original sources

The regenerating liver: a site of erythropoiesis in the adult Long-Evans rat.

Erythropoiesis, which is primarily hepatic in the rat during fetal and early neonatal life, shifts almost entirely to the bone marrow in the neonatal-adolescent stage of development. In the adult, extramedullary erythropoiesis has been demonstrated in the liver and spleen under certain pathological conditions when bone marrow red cell production is insufficient. In the present study, erythropoietic foci have been found in young-adult rat liver regenerating 24-72 hr after subtotal hepatectomy. This erythropoiesis is both extravascular and sinusoidal, with some erythroblastic islands noted. The centrolobular hepatic area contains the highest concentration of erythroblasts. Peripheral blood reticulocytosis coincides with the appearance of these cells and this is considered as an indicator of effective erythropoiesis. Liver regenerating after partial hepatectomy produces significant quantities of erythropoietin (Ep) in response to hypoxia. Subtotal hepatectomy may confer upon the adult liver the ability to revert to a fetal-like condition both in its ability to produce Ep and to function as a hematopoietic inductive microenvironment for erythropoiesis.

Age Factors↗

Phosphorylation of the membrane-bound acetylcholine receptor: inhibition by diphenylhydantoin.

Purified postsynaptic membranes can be used as a model system to study the regulation of synaptic membrane proteins. These membranes contain protein kinase activity that phosphorylates the acetylcholine receptor (AChR). We find that diphenylhydantoin (DPH) interacts with these membranes to inhibit phosphorylation of the membrane-bound AChR. DPH appears to alter the availability of postsynaptic membrane proteins for phosphorylation by a synaptic membrane protein kinase. The concentration of DPH that produces half-maximal inhibition of AChR phosphorylation is about 5 x 10(-5) M. This suggests that one of the specific effects of DPH in the nervous system may be related to inhibition of phosphorylation of postsynaptic membrane proteins.

Animals↗

Reticuloendothelial system (RES) hyperfunction and erythropoietin (Ep) production in the regenerating liver.

Hepatic cells in rats were evaluated after subtotal hepatectomy using scintillation scanning with technetium sulfur colloid (TSC), autoradiography, and microstereology techniques. The ability of the liver to accumulate TSC increased during the course of the regeneration as did the labeling of Kupffer and parenchymal cells with tritiated thymidine (3H-tdR). Kupffer to parenchymal cell number ratios and Kupffer cell relative areas were also elevated, attaining peak values at 72 hours post-hepatectomy. This period corresponds to the time of peak erythropoietin (Ep) production in rats with regenerating livers after nephrectomy and exposure to hypoxia. These findings suggest that the Kupffer cell may function as a cellular site of Ep formation.

Animals↗

Studies of nuclear proteins in the skeletal muscle of the cardiomyopathic Syrian hamster.

Nonhistone nuclear proteins (NHNP) were isolated from the skeletal muscle of dystrophic hamsters and their respective paired controls. These proteins were extracted with phenol and fractionated by polyacrylamide gel electrophoresis. One-dimensional gel electrophoresis using either sodium-dodecylsulfate or isoelectrofocusing revealed quantitative changes between the two groups. An improved resolution using a two-dimensional system showed both quantitative and very limited qualitative differences. There are differences in proteins focusing at pH 5.0, molecular weight 55,000, in the dystrophic tissue. In addition proteins from dystrophic muscle focusing between pH 5.0 and 7.0, molecular weight 45,000, and proteins focusing between pH 7.0 and 9.0, molecular weights 35,000--45,000 and 60,000--70,000 were reduced as compared to the controls. There were no detectable differences in the electrophoretic patterns between the two groups of proteins derived from skeletal muscle homogenates. The differences in NHNP appear to be reflections of alterations in the nuclear composition of the dystrophic muscle cell. Some of these differences may represent changes secondary to the muscle disease. However, if NHNP interacting with DNA play a major role in the control of genetic expression, some of the manifestations of hamster dystrophy could be due to a different constitution of NHNP in the skeletal muscle.

Animals↗

Erythropoiesis and artificial blood substitution with a perfluorocarbon-polyol.

Rats were perfused with Fluosol-43, a perfluorotributylamine-pluronic F-68 emulsion, to produce hematocrits of about 6% and the mechanisms of blood cell replacement were studied. The packed RBC volume and number of RBCs per cubic millimeter increased gradually as the time after perfusion was completed until reaching the preperfusion level at about 1 week. The WBCs per cubic millimeter, which were not as severely depleted because of their vast storage compartment, increased to preperfusion levels by 24 hr and continued to increase through 7 days. Plasma did not show significant Ep activity until 48 to 72 hr after perfusion was concluded. Thus, although 90% of the RBCs were removed, elevated erythropoietin activity was not detected immediately because the perfluorocarbon compound replaced the capacity of the RBCs as an oxygen and carbon dioxide carrier.

Animals↗

Erythropoietic response of hypertransfused neonatal rats suckled by anemic mothers.

Twelve-day-old hypertransfused neonatal rats nursed for four days by a twice-bled mother exhibited higher 48-hour RBC-59Fe incorporation than control neonates nursed by a normal mother. Erythroprotein (Ep) in plasma of 12-day-old hypertransfused neonates suckled for four days to twice-bled mothers was initially equivalent to approximately 0.5 IU/day. This calculation was based on the observation that reticulocytosis induced in these animals was similar to that produced in neonates of the same age injected intraperitoneally with 0.5 IU Ep for four days while nursing from normal mothers. The reticulocyte maturation curve was shifted to the left in 12-day-old hypertransfused neonates suckled by anemic mothers, and in 12-day-old normal neonates rendered anemic by bleeding, while nursing from normal mothers. This left-shift of the reticulocyte maturation curve was also evident in 12-day-old hypertransfused neonates injected with Ep. Decreases in relative percentages of nucleated RBC was evident in spleens of 12-day-old neonates nursed by anemia mothers and spleens of 12-day-olds injected with Ep. Significant reduction in nucleated RBC were noted in both spleen and marrow of 12-day-old anemic neonates. These results suggest: (1) Ep, present in increased amounts in the anemic mother, is transmitted through milk to nursing neonates thereby stimulating erythropoiesis in these animals; (2) Ep may not stimulate stem cell differentiation towards the e4ythroid compartment but rather acts on already differentiated erythroid cells by influencing their rate of maturation.

Anemia↗

Effect of phenylhydrazine pretreatment on splenectomized Rauscher leukemia virus-infected mice.

The protective effect of phenylhydrazine pretreatment seen in Rauscher leukemia virus-infected intact mice is not observed when splenectomized mice are used. Such mice succumb to infection even earlier than viral potency controls. Since phenylhydrazine is known to increase both splenic erythropoiesis and hematopoietic stem cell numbers, the results suggest that these two events may be involved in phenylhydrazine prophylaxis.

Animals↗

Chromosomal evidence for the transplantability of the Shay chloroleukemia.

Chloroma cells, which were shown to contain the X and Y chromosomes, were used to induce Shay chloroleukemia (SCL) in female recipients. Karyotype analyses of leukemic myeloblasts which appeared in the peripheral blood of the female recipients during blast crisis demonstrated invariably the presence of the X and Y chromosomes. These results directly demonstrate that transmission of SCL is the result of donor cell colonization and therefore SCL can be considered a true transplantable leukemia. Reports by other workers of viral association with this disease are discussed in light of our results.

Animals↗

The effects of maternal phlebotomy and orally-administered erythropoietin (Ep) on erythropoiesis in the suckling rat.

Erythropoiesis was stimulated in 2- to 5-day-old neonatal rats suckled by phlebotomized mothers. This was established by increases in: hemoglobin levels, mean corpuscular hemoglobin concentration and percentages of peripheral reticulocytes. The oral administration of cow milk containing 4 IU human erythropoietin (Ep) to 10-day-old normal neonates for 4 days induced a reticulocytosis. Significant amounts of Ep appeared in the plasma of 1-day-old rats nursed by mothers bled 3 days prior to delivery as compared to nondetectable levels in 1-day-old control rats of normal mothers. The data suggest that Ep is transmitted to neonatal rats via maternal milk, and escapes inactivation, at least to some extent, in the process of absorption from the gastrointestinal tract with consequent stimulation of erythropoiesis in these animals.

Administration, Oral↗