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Biomedical subjects

F Beck

Publications and source records attributed to F Beck.

At least 109 records · Page 6Linked to original sources

Control of IGF-II mRNA levels by glucocorticoids in the neonatal rat.

Insulin-like growth factor-II (IGF-II) is thought to be a major growth factor during fetal and neonatal development. Levels of IGF-II mRNA fall dramatically in the liver - the major site of endocrine production - between 18 and 20 days post-natally. No information concerning the control of gene expression post-natally has hitherto been available. Using Northern blotting and in-situ hybridization, we show here that cortisone acetate rapidly extinguishes IGF-II mRNA expression in the neonatal rat liver. The effect at putative autocrine/paracrine locations such as skeletal muscle and choroid plexus is much less marked or absent. The repression by cortisone acetate is discussed in the light of the available IGF-II gene sequence.

Animals↗

The effects of mannose on rat embryos grown in vitro.

Rat embryos have been cultured in vitro from 9.5 days of gestation for different times in serum containing mannose, and the embryos have been observed by scanning electron microscopy. Embryos cultured in 3 mg/ml (1.7 X 10(-2) M) or 6 mg/ml (3.3 X 10(-2) M) mannose for 48 h showed inhibition of the expansion of the yolk sac and were smaller than the control embryos. Mannose-treated embryos also showed delayed development according to morphological criteria, and a range of abnormalities including abnormalities of the neural tube. Embryos cultured in 6 mg/ml mannose for 24 h also showed significant inhibition of yolk-sac expansion and were smaller and less advanced than the control embryos. Abnormalities were seen, including a delay in the closure of the neural folds. Abnormalities were also observed in embryos cultured in mannose for 10 h; embryos at the neural groove stage showed irregularities in the neural groove. Mannose did not inhibit the re-elevation of neural folds which had been caused to collapse by exposure to medium containing low calcium. These results are compatible with the idea that mannose retards development and thereby perturbs the morphogenesis of the neural tube.

Animals↗

A stage-dependent effect of ethanol on 9.5-day rat embryos grown in culture and the role played by the concomitant rise in osmolality.

The effects of ethanol on the rat embryo undergoing organogenesis in vitro have been studied. We have shown that embryopathy is dependent on the stage of development at which explanted embryos were treated. The early neural plate (presomite) stage was highly sensitive to a 4-hour exposure of 300 mg/% ethanol, whereas embryos explanted 5 hours later, at the late head-fold (two to six somites) stage grew normally under the same conditions. We have also established that raised serum osmolality, associated with ethanol in serum, is responsible for some but not all of the teratogenic effect. This was shown by mimicking the rise in osmolality with hyperosmotic serum, containing glycerol, NaCl, or concentrated Hanks' salts. Dilution of this osmotic effect by the addition of distilled water in part reversed these embryopathic effects.

Abnormalities, Drug-Induced↗

Histochemical localization of IGF-I and -II mRNA in the developing rat embryo.

We describe the histological localization of embryonic and fetal tissues whose cells express the genes coding for insulin-like growth factors I and II (IGF-I and IGF-II) in the developing rat. Our studies span the period between early somite stages and full term. We have used oligodeoxyribonucleotide probes and obtained results which are both topographically precise and highly reproducible. The gene coding for IGF-II is predominant throughout development. It is strongly expressed in the liver and yolk sac. A variety of other tissues also expresses the IGF-II gene, especially many mesodermally derived structures in the process of differentiation. Many tissues do not express IGF genes. Thus no IGF mRNA was demonstrable in ectodermally derived structures, including the central and peripheral nervous systems as well as the skin and its derivatives.

Animals↗

Effect on rat embryos of in vitro culture in sera from human diabetic patients.

Recently conditions have been established whereby rat embryos can be cultured in vitro in human serum over the period of their major morphogenesis. By standardizing the amount of glucose in sera from diabetic subjects prior to culture, it has been possible to investigate factors other than hyperglycemia which might account for the increased incidence of congenital defects seen in infants of diabetic mothers. The incidence of abnormalities in rat embryos cultured in sera from chlorpropamide-treated diabetics was not significantly different from that using control sera from normal subjects. On the other hand, sera from insulin-dependent diabetics produced more defects in rat embryos than sera from either normal subjects or diabetics on oral agents. The incidence of abnormal rat embryos does not appear to be correlated with patient age, with the original blood glucose concentration or with the concentration of hemoglobin A1 or, in the insulin group, with the total daily insulin dosage.

Animals↗

The giant yolk sac: a model for studying early placental transport.

Nine and a half day rat embryos can be cultured for 48 hours in whole heat-inactivated rat serum using the roller culture method described by New, Coppola & Terry (1973). We have prolonged the culture period, usually by seven days. Although the embryo dies almost immediately during this extended culture period, the yolk sac continues to grow and reaches a diameter of approximately 2 cm; we have called this the giant yolk sac. The morphology of the giant yolk sac is very similar to that of control yolk sacs (17 1/2 or 18 1/2 days in vivo), the main difference being the greatly enlarged vacuolar volume in the endodermal cells of the giant yolk sac, which have been studied morphometrically. The pinocytic nature of the giant yolk sac has been demonstrated by its ability to take up colloidal gold. Its rate of uptake of 125I-polyvinylpyrrolidone in whole serum gassed with 95% O2; 5% CO2 has been shown to be similar to the rate of uptake found in control yolk sacs under the same incubation conditions. Acid phosphatase activity was found to be similar in the giant yolk sac and control yolk sacs using both histochemical and biochemical methods. Giant yolk sacs without a contained dead embryo can be produced by removing the embryonic pole of the egg cylinder prior to incubation. They exhibit all the features detailed above. Finally it is shown that the fluid from within the extra-embryonic coelom of the giant yolk sac has some capacity to support the growth and development of 9 1/2 day rat embryos when a source of bulk protein is also provided. This model, therefore, seems to be very useful for the study of transport in a placental system. Its full potential requires further study.

Acid Phosphatase↗

Effects of diltiazem on hormonal and hemodynamic responses to lower body negative pressure and tilt in patients with mild to moderate systemic hypertension.

Mean arterial blood pressure, forearm vascular resistance, plasma norepinephrine, plasma renin activity and aldosterone responses to graded lower body negative pressure and tilt at 80 degrees were examined in 10 men with mild to moderate essential hypertension before and after 12 weeks of diltiazem (240 to 360 mg/day) therapy. Diltiazem therapy lowered basal supine systolic and diastolic blood pressures without affecting basal heart rate. Mean arterial blood pressure and forearm vascular resistance were decreased from 114 +/- 1.5 to 105 +/- 1 mm Hg, p less than 0.01 and from 29.3 +/- 3.5 to 18.9 +/- 2.1 units, p less than 0.01, respectively. Diltiazem therapy had no effect on basal supine levels of norepinephrine, plasma renin activity or aldosterone, nor on the responses of these hormones to lower body negative pressure. Diltiazem did decrease the forearm vascular resistance responses to lower body negative pressure and tilt. Diltiazem abolished an orthostatic increase (10 +/- 0.3 mm Hg) in mean arterial blood pressure and this was associated with a greater plasma norepinephrine response to tilt. These results suggest that diltiazem decreases vascular resistance through a reduction in the postjunctional effects of norepinephrine on vascular smooth muscle.

Adult↗

Effects of beta-hydroxybutyrate on rat embryos grown in culture.

In order to investigate further the relationship between maternal diabetes and fetal malformation, rat embryos were grown in vitro in the presence of beta-hydroxybutyrate, one of the ketone bodies produced by diabetics. At 10 mM, beta-hydroxybutyrate produced minor abnormalities and at 20 mM it produced major abnormalities in rat embryos.

Abnormalities, Drug-Induced↗

Cl transport across the basolateral membrane in frog skin epithelium.

Cellular Cl concentrations were determined by electron microprobe analysis to obtain further insight into the Cl transport across the basolateral membrane of the frog skin epithelium. Cl-free media on the serosal side led in all epithelial layers within 1 h to a decrease in cellular Cl concentration from about 40 to 15 mmol/kg wet wt, whereas the application of Cl-free solutions or amiloride to the apical side had no effect. Na-free media, furosemide or bumetanide on the serosal side had little effect on cellular Cl but abolished the Cl-reuptake into Cl-depleted cells. It is concluded that cellular Cl concentration is maintained above electrochemical equilibrium by a co-transport system, which is relatively silent under control conditions.

Animals↗

Osmoregulation of renal papillary cells.

Element concentrations were determined in various extra- and intracellular compartments of the rat renal papilla in antidiuresis and after furosemide-induced diuresis using electron microprobe analysis to elucidate further how the cells adapt osmotically to different osmolalities. In antidiuresis and diuresis the sum of intracellular cations (sodium and potassium), accompanying anions and urea was insufficient in both cases to provide cell osmolalities similar to those in extracellular compartments. This finding provides further evidence that the papillary cells achieve osmoadaptation to widely differing extracellular electrolyte concentrations mainly by varying the cellular concentrations of osmotically-active substances other than urea and electrolytes.

Animals↗

Electron microprobe analysis of proximal tubule cellular Na, Cl and K element concentrations during acute mannitol-saline volume expansion in rats: evidence for inhibition of the Na pump.

It has previously been shown that during mannitol-saline volume expansion (VE) Na transport was inhibited 50% by harvested proximal tubular fluid without a change in paracellular shunt pathway permeability to Na. To determine whether this inhibition was due to changes in cellular entry step or an effect on the pump itself, intracellular element concentrations were measured by electron microprobe X-ray ranalysis in proximal tubular cells of control (non-expanded, NE) and VE rats. Nai, Cli and phosphorusi were increased (mean +/- S.E.) from 19.3 +/- 0.8 to 23.4 +/- 0.6, 15.8 +/- 0.4 to 21.3 +/- 0.4 and 124.3 +/- 2.6 to 138.0 +/- 1.8 mmol . kg-1 wet weight (P less than 0.001) respectively while Ki remained unchanged: 122.9 +/- 2.2 and 124.2 +/- 1.3 mmol . kg-1 wet weight. The increases in Nai and Cli were in excess of cell shrinkage produced by the hyperosmolal peritubular environment while the unchanged Ki in the face of cell shrinkage indicates and actual loss. It is concluded that mannitol-saline VE inhibits the Na pump producing a rise in Nai and a fall in Ki.

Animals↗

Maternal transferrin uptake by and transfer across the visceral yolk sac of the early postimplantation rat conceptus in vitro.

Uptake and transfer of maternal transferrin by rat embryos during organogenesis in vitro was investigated using radiolabelled rat transferrin and rocket immunoelectrophoresis. Colloidal gold to which rat transferrin was adsorbed was used as an electron microscopical marker in order to follow the route taken by internalised transferrin across the visceral yolk sac. Culture of rat conceptuses from 9.5 to 11.5 days of gestation in rat or human sera resulted in the passage of rat or human transferrin from the culture medium into the extraembryonic coelom as determined by quantitative immunoelectrophoretic analysis of exo-coelomic fluid. The concentration of human transferrin which was transferred to the exo-coelomic fluid of conceptuses cultured in whole human serum at 10.5 days and 11.5 days of gestation was similar to the concentration of rat transferrin in the fluid of conceptuses cultured in rat serum which had been diluted with Hanks' saline to 50% in order to match the levels of transferrin found in human serum. Growth of rat embryos in 50% rat serum was identical to embryonic growth in 100% rat serum. Uptake of radiolabelled rat transferrin by the visceral yolk sac at 11.5 days of gestation, following culture for 60 min in radiolabelled medium, was much greater than nonspecific uptake of radiolabelled bovine serum albumin. Accumulation of radiolabelled transferrin by the embryo was reduced by the inclusion of unlabelled transferrin into the culture medium. Uptake of transferrin adsorbed 18 nm gold particles was mediated by attachment to coated pits on the apical cell surface of the extraembryonic endoderm. Transferrin-adsorbed gold colloid was internalised via coated vesicles and found in cisternal structures of the peripheral and juxtanuclear areas, as well as in smooth and coated vesicles deep within the cell. The intercellular presence of gold particles in the endodermal layer of the visceral yolk sac and their presence in the mesoderm after 60 min of incubation suggested that passage of transferrin was rapid and mediated by vesicular evagination from the extraembryonic endoderm. These findings suggest that maternal transferrin is the primary source of transferrin for the early rat embryo and its passage to the exo-coelom and embryo is mediated by specific receptors on the apical surface of the extraembryonic endoderm.

Animals↗