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Biomedical subjects

C Peschle

Publications and source records attributed to C Peschle.

At least 217 records · Page 12Linked to original sources

Fluctuations of BFUe and CFUe cycling after erytrhoid perturbations: correlation with variations of pool size.

The pool size of erythroid burst-(BFUe) and colony-forming units (CFUe) has been evaluated in normal or hypoxia-induced polycythemic mice at sequential times after either transfusion or administration of purified erythropoietin (Ep). The present investigations were focused on the in vitro tritiated thymidine (3H-TdR) suicide index of the erythroid precursors in these two experimental models. After transfusion an early but transient decline of the DNA sythesis index was observed in the BFUe pool, whereas this parameter showed a later, more prolonged decrease within the CFUe population. Symmetric patterns were documented after Ep injection: an early, transient elevation of the 3H-TdR sensitivity at the BFUe level and a late, more persistent rise within the CFUe compartment. In all experiments no modification of this indes was observed within the pool of the CFUe. These fluctuations of BFUe and CFUe cycling were temporally consistent with modifications of their respective pool size, as previously reported. Thus, variations of the pool size may be at least partially mediated by the cycling activity. Furthermore, early fluctuations of BFUe proliferative rate indicate that, after erythroid perturbations, this pool may initially be sensitive to and regulated by modifications of Ep activity. Later, however, compensatory mechanisms allow the BFUe to escape from this early Ep influence, thus leading its cycling activity and pool size to return to normality and stabilize.

Animals↗

Early fluctuations of BFU-E pool size after transfusion or erythropoietin treatment.

The kinetics of erythroid burst-(BFU-E) and colony-forming units (CFU-E) have been evaluated in marrow and spleen of normal or polycythemic mice, respectively, after transfusion or administration or purified erythropoietin (Ep). Ep injection induces an early but temporary rise of BFU-E number, versus a later but more prolonged expansion of the CFU-E pool. Symmetric patterns are observed after transfusion, i.e., an early but transient depletion of the BFU-E population, versus a later but more persistent decrease of the CFU-E number. It is suggested that the size of the BFU-E compartment is Ep-dependent in the "early" phase after erythroid perturbation. Later on, however, compensatory mechanisms allow the BFU-E pool to "escape" from the early Ep influence, thus allowing its size to return to and stabilize in the near normal range. It is further suggested that the BFU-E may represent an early target cell of Ep stimulus.

Animals↗

Paraproteinemic variety of pure red cell aplasia: immunological studies in 1 patient.

A case of adult pure red cell aplasia (PRCA) with a serum IgG inhibitor to erythropoiesis and an IgG lambda M component is presented. The study of lymphocyte populations revealed a slight but definite decrease of E and EA rosettes, with dissociation between E rosettes and PHA blastic transformation of blood lymphocytes and increase of membrane IgM-bearing lymphocytes. The relationship between PRCA and paraproteinemia is discussed: it is suggested that the serum M component may derive from an immunological unbalance between T and B lymphocytes. Since a survey of the literature reveals 5 similar cases, it is suggested that paraproteinemia may be the hallmark of a particular variety of chronic PRCA 'type 1'.

Aged↗

Role of the hypophysis in erythropoietin production during hypoxia.

Hypophysectomized or sham-operated male rats were exposed to hypoxia (0.42--0.40 or 0.37--0.35 atm for 6, 12, or 24 hr) applied 2 wk to 7 mo after surgery. Erythropoietin (Ep) levels in rat serum were evaluated on the basis of the exhypoxic polycythemic mouse assay. Ep activity evoked by hypoxia was significantly lower in hypophysectomized rats than in sham-operated controls. Progressive increase of the EP response to hypoxia correlated with extension of the time interval between hypophysectomy and hypoxia from 2 wk to 2--4 mo apparently mediated by the simultaneous inverse decline of red cell mass (RCM) values, i.e., of the "relative plethora" induced by a low O2 demand associated with relatively high RCM values. However, after 3--7 mo hypoxic Ep activity was still lower than in sham-operated controls. In these ablated animals the relative plethora became negligible or absent; accordingly, the Ep response apparently had reached plateau levels. These studies indicate that hypophysis (hypophyseal and target hormones, with the exception of estrogens) modulates Ep production under hypoxic conditions, possibly via a permissive enhancement of renal Ep activity.

Animals↗

Kinetics of erythroid and myeloid stem cells in post-hypoxia polycythaemia.

The number of erythroid burst-(BFU-E) and colony-forming units (CFU-E), as well as of myeloid-macrophage colony-forming units (CFU-C), has been evaluated in tibial marrow and spleen of ex-hypoxic polycythaemic mice, at sequential time intervals after the end of hypoxia. In both marrow and spleen, the kinetics of the CFU-E pool is characterized by a sharp fall from above normal to lower than normal values. BFU-E and CFU-C however rise from below normal to higher than normal levels. These results have been correlated with both the erythropoietin (Ep) and the erythropoietic activity curves. It is apparent that Ep levels largely control both the differentiation and the amplification of the CFU-E pool and it is suggested that Ep may act as a 'survival factor' at the CFU-E level and/or increase the flow of cells from BFU-E to CFU-E. The difference in response between CFU-E and BFU-E favours a clearcut distinction between these populations, whereas the similarity between the BFU-E and CFU-C response suggest a close relationship between these two cell populations. It is also of interest that the murine spleen functions as a large reservoir of erythroid microenvironment for hypoxia-induced stress erythropoiesis.

Animals↗

Myocardial contractility after injection of prolonged infusion of magnesium sulphate.

The effect of magnesium sulphate administration on myocardial inotropism has been evaluated by means of the noninvasive indexes of myocardium contractility in 18 patients affected by myocardiosclerosis associated with signs of cardiac impairment of different degree. Magnesium has been administered via either a prolonged infusion (30-50 mg/min) or a single injection (2.5 g/30 sec). It is emphasized that the influence of this agent on systolic time intervals (STI) is dependent upon its route of administration. Thus, prolonged infusion does not modify significantly these parameters, whereas a single injection induces marked variations, i.e., decrease of LVET, increase of PEP, ICT and PEP/LVET ratio, which are all more marked in cases of severe cardiac impairment. In view of the strict correlation established between the STI and the invasive indexes of myocardial contractility, it is suggested that administration of magnesium sulphate via prolonged infusion does not induce a decrease of cardiac performance, while a single injection of this agent leads to this effect.

Arrhythmias, Cardiac↗

Hepatic erythropoietin: enhanced production in anephric rats with hyperplasia of Kupffer cells.

Erythropoietin (Ep) levels were assayed in serum of adult male rats subjected sequentially to (1) administration of colloidal carbon, Zymosan or their vehicles (2) sham operation or bilateral nephrectomy with and without subtotal hepatictomy, and (3) hypoxia (0.45-0.40 atmospheres of air for 6 h starting 1 h after the operation). In anephric rats these agents induced a significant potentiation of hypoxic Ep activity. Since they did not apparently modify the kinetics of exogenous Ep, it is postulated that this phenomenon is mediated by enhanced extrarenal Ep production. Both colloidal carbon and Zymosan induced hyperplasia of the reticuloendothelial system (RES). Moreover, subtotal hepatectomy almost abolished the Ep response to hypoxia evoked by Zymosan. The correlation between hyperplasia of hepatic RES and enhanced Ep production in anephric rats primed with these agents suggests that Kupffer cells constitute a major source for extrarenal Ep. Additionally, it is of interest that colloidal carbon and Zymosan did not significantly modify the renal production of Ep.

Animals↗

Erythropoietin production in the rat: additive role of kidney and liver.

Erythropoietin (Ep) levels were evaluated in serum of neonate, weanling, or adult rats subjected to 1) sham operation, nephrectomy, and/or subtotal hepatectomy and 2) a standard bout of hypoxia (0.45 atm air/6 h, starting 1 h after the operation). Ep activity was quantitated by means of strictly controlled assays in exhypoxic polycythemic mice. The sum of Ep titers in the serum of nephrectomized or hepatectomized rats was compared to Ep levels in sham-operated animals of corresponding age levels, with the exception of 1-wk-old rats: it is relevance that no significant difference is apparent between these Ep production curves. Thus, evidence is presented indicating for the first time that Ep derives from two functionally distinct and additive sources, i.e., the kidney and the liver. Liver Ep, although prevalent in neonatal animals, is obscured in the weanling adult rat by both gradual initiation of massive renal Ep production and progressive decrease of hepatic Ep activity.

Age Factors↗

Increased erythropoietin production in anephric rats with hyperplasia of the reticuloendothelial system induced by colloidal carbon or zymosan.

Adult rats were subjected sequentially to (1) administration of colloidal carbon, zymosan, or gadolinium; (2) subtotal hepatectomy, bilateral nephrectomy, or sham operation; and (3) a 6-hr bout of hypoxia, starting 1 hr or 24 hr after the operation. Control animals received the respective vehicles. The erythropoietin (Ep) activity was assayed in exhypoxic polycythemic mice on the basis of 48-hr per cent RBC(-59) Fe incorporation values. Ep levels in serum of anephric rats primed with either colloidal carbon or zymosan were considerably more elevated than in control animals. This potentiating effect was observed in rats subjected to hypoxia starting either 1 or 24 hr after nephrectomy. On the other hand, gadolinium did not enhance the extrarenal Ep response to hypoxia. It is emphasized that both colloidal carbon and zymosan induced marked hyperplasia of the hepatic and splenic reticuloendothelial system (RES), while gadolinium did not induce this effect. A strict correlation was thus established between potentiation of extrarenal Ep production and hyperplasia of the RES. It is therefore tentatively concluded that the RES is a source of extrarenal Ep. Additionally, since the liver plays a prominent role in extrarenal Ep production, Kupffer cells may represent a major source for Ep in the anephric rat. Finally, it is of interest that both colloidal carbon and zymosan did not potentiate the Ep response to hypoxia in sham-operated or subtotally hepatectomized rats.

Animals↗

Biogenesis of erythropoietin: evidence for pro-erythropoietin in a subcellular fraction of kidney.

The light mitochondrial fraction of hypoxic rodent kidneys, called the renal erythropoietic factor, contains erythropoietin in a pro, or active form. Erythropoietin is released from this inactive form when the renal erythropoietic factor is incubated with normal serum. The biogenesis of erythropoietin possibly involves a system in kidney reminiscent of the proinsulin-insulin system in pancreas.

Animals↗

[Demonstration of 2 experimental models of pure chronic erythroblastopenia].

Two experimental models for pure red cell aplasia (PRCA) were established. In the first one, administration of PRCA serum IgG in normal mice induced a sustained inhibitory effect on erythropoiesis, a progressive decline of the hematocrit values and an inverse rise of erythropoietin (Ep) levels in serum. Thus, the physiopathological pattern of PRCA type I (or A) was established, In the second model a rabbit producing anti-Ep crossreacting with endogenous Ep was subjected to a booster injection of Ep. The rise of the immune response was associated with decrease of Gct values and disappearance of erythroid precursors from marrow smears, and its subsequent decline with reticulocytosis and regression of the anemia, thus reproducing the physiopathological pattern of PRCA type II (or B).

Anemia, Aplastic↗