摘要:

ExtractCarbohydrate metabolism of skeletal muscle from rhesus fetuses at 58% of gestation (95 days) is sensitive to epinephrinein vitro.Epinephrine increased lactate production and decreased glucose uptake,14C-lactate production, glycogen content, and14C-glycogen formation as well as14CO2production. These responses to epinephrine are similar to those in adult muscle. However, in some cases the magnitude of these responses appears lower in fetal muscle. The content of cyclic14C-adenosine 3‘,5’-monophosphate (cyclic14C-AMP) was about 2.5-fold higher in the 100-day fetal muscle than in the adult. Epinephrine stimulated adenylate cyclase activity almost threefold in fetal and fourfold in adult muscle. When incubated with muscle from 85-day fetal monkeys, insulin increased glucose uptake, lactate and lactate-14C production, and14CO2production; the greatest effect was found in the increased incorporation of labeled glucose into glycogen. Both synthetase I and phosphorylaseaactivities were present at 78–80 days of fetal age. Our data show that as early as about 58% of term the carbohydrate metabolism of fetal rhesus musclein vitrois sensitive to epinephrine and that the hormone probably acts through the adenylate cyclase and the “second messenger” system of cyclic AMP as it does in adult muscle.SpeculationOur data offer indirect evidence that insulin and epinephrine mediate glycogen metabolism via cyclic AMP in rhesus fetal muscle as early as 85 days of gestational age (52% of term) and that these hormones operate through similar enzyme systems in fetal and adult muscle. It is possible that glycogen synthetase and phosphorylase, or other enzymes mediating the cyclic AMP response, are not identical in fetal and adult muscle; fetal isoenzyme patterns for muscle lactate dehydrogenase differ markedly from those of the adult. However, it is difficult to reconcile the existence of major differences in the enzyme milieu in fetal and adult muscle with the similar overall actions of epinephrine and insulin on glycogenesis and glycogenolysis demonstrated in our experiments.

ISSN:0031-3998    

出版商:OVID    

年代:1973

数据来源: OVID

摘要:

ExtractGlucose/oxygen quotients were determined across the hindlimbs of seven fetuses, for a total of five studies in fetuses of fed ewes and five studies in fetuses of fasted ewes. The glucose/oxygen quotient was found to be a function of the fetal arterial glucose concentration in mM, [a], described by the equation: glucose/oxygen quotient = - 0.047 + 1.46[a]. The dependence of glucose uptake by the fetal hindlimb upon arterial glucose concentration is the first demonstration of the effect of substrate availability on the metabolism of a fetal organ.SpeculationThe demonstration of glucose/oxygen quotients of 1.0 or greater for fetal tissues at a time in gestation when the umbilical glucose/oxygen quotient is 0.4–0.5 suggests two possible explanations: (1) there may be substrate specificity for oxidative metabolism for each fetal organ, and (2) non-glucose substrates such as amino acids taken up by the umbilical circulation may be utilized by the fetal liver for gluconeogenesis.

ISSN:0031-3998    

出版商:OVID    

年代:1973

数据来源: OVID

摘要:

ExtractHuman term placental lysosomes have been isolated and their quantitative density distribution has been established by biochemical and morphologic analysis. Histologic examination of placental villi after passage through the tissue press reveals minimal contamination due to platelets and leukocytes. Fluorescence microscopy with acridine orange demonstrates lysosomes in the syncytium. Differential centrifugation yields two lysosome populations. One segregates with endoplasmic reticulum, whereas the other is similar to lysosomes isolated from other tissues. The classic lysosomes have a peak density of 1.195 g/ml and are heterogeneous with respect to size and distribution within the density gradient. Acid phosphatase is differently distributed than the other acid hydrolases and is not a suitable marker for placental lysosomes. The enzyme cleaving glucose 6-phosphate is broadly distributed and not necessarily identical with the glucose 6-phosphatase (EC. 3.1.3.9) of other tissues. Peroxisomes are absent from term placenta.SpeculationPlacental lysosomes are considered to play a role in fetal-maternal transport, cellular differentiation, and remodeling. The organelle may be affected by sequential fluxes in steroidal sex hormones. Present knowledge of the characteristics of placental lysosomes and their role in these physiologic processes is limited. Isolation and characterization of lysosomes from placentas of different gestational ages will provide answers to these questions.

ISSN:0031-3998    

出版商:OVID    

年代:1973

数据来源: OVID

摘要:

ExtractChemical and biochemical variables of the sphingolipids were examined in fetal liver, kidney, and brain using saline-aborted (SA) and hysterotomy-aborted (HA) tissues. Brain sphingolipid hexose (BSH) and gangliosideN-acetyl neuraminic acid (NANA) content were similar in each group (BSH/SA, 4.1–5.0 mg/g dry wt and HA, 3.0–6.7 mg/g dry wt; NANA/SA, 1.1–3.3 mg/g dry wt and HA, 1.3–3.1 mg/g dry wt). The distribution of the major gangliosides was also comparable in each group. Sulfatide levels were lower in the hysterotomy group (0.2–0.4 mg/g dry wt) than in the saline group (0.5–0.9 mg/g dry wt), perhaps reflecting the earlier gestational age of this group. Activities of arylsulfatase A (ARA), β-galactosidase, and hexosaminidase A from each tissue were similar, respectively, in saline-and hysterotomy-aborted fetuses. The ARA activity (liver, 23–67; kidney, 13–21; and brain, 1–42 nmol cleaved/mg protein/hr) was about 10–20% of postnatal levels. Utilizing these control values, amniocentesis-derived diagnoses were confirmed in two fetuses with Tay-Sachs disease (TSD) and in another with Gm1gangliosidosistype I.The disease-specific ganglioside (Gm2in TSD and Gm1in Gm1-gangliosidosis) was significantly elevated in brain from each case (TSD, 5–6 times control values and Gm1-gangliodosis, approximately twice control values). In liver and kidney from the affected fetuses the disease-related enzyme activity of hexosaminidase A in TSD and β-galactosidase in Gm1-ganglactosidase) was less than 10% of control values. In liver, kidney, and brain extracts, cellulose-acetate gel electro-phoresis of the disease-specific enzyme revealed no bands of enzyme activity for hexosaminidase A in Tay-Sachs disease or for the relevant, β-galactosidase isoenzymes in Gm1-gangliosidosis.SpeculationThe prenatal diagnosis of Tay-Sachs disease, Gm1-gangliosidosis, and other sphingolipidoses may be confirmed in saline-aborted fetal tissues. Since abortion by hysterotomy may jeopardize the possibility of future pregnancy, saline-induced abortion may be preferable. An intriguing observation of this study was the presence of a β-galactosidase isoenzyme in brain from the Gm1fetus. This isoenzyme was clearly different from the disease-specific enzyme and was not present in fetal Gm1liver or kidney or in postnataltype IGm1brain. This finding may indicate the presence of a tissue and age-specific β-galactosidase isoenzyme.

ISSN:0031-3998    

出版商:OVID    

年代:1973

数据来源: OVID

摘要:

ExtractL-Proline transport and metabolism have been investigated in normal adult human kidney cortical slices. The uptake of proline from buffers containing both high (10 mM) and low (0.23 mM)14C-proline concentrations is intimately related to the extent of intracellular proline metabolism. The accumulation of radioactivity from both the 10 and 0.23 mM proline media was against high radioactivity gradients, with distribution ratios of 18 and 3, respectively. Recovered proline from the intracellular fluid (IGF) accounted for less than 12% of the intracellular radioactivity in the tissue extracts. Glutamic acid accounted for greater than 75% of the intracellular form of the soluble radioactivity in tissue extracts. Total oxidation to14CO2from both proline concentrations accounted for more than 50% of the total proline taken up by the slices.Kinetic analysis of the entry process suggested the existence of two saturable systems: one operative at low or physiologic proline concentrations (apparentKm2 mM) with a low capacity (Vmax40 μM-ml ICF-1-30·min-1) and shared with neutral amino acids, and a second with an affinity to 10-fold less (apparentKm17 mM) with a high capacity (Vmax160 μM·ml ICF-1·30 min-1) and unshared by the neutral amino acids. Separation of the influence of metabolism from the analysis of the transport systems by the use of proline analogues showed that thioproline inhibited proline uptake by 80%, primarily by reducing the conversion of proline to glutamic acid, whereas 3,4-dehydroproline did not affect the conversion of proline to glutamic acid but principally appeared to alter the affinity of the transport system for proline.SpeculationThese studies suggest that changes in the rate of proline metabolism in the human kidney may alter the rate of tubular reabsorption, thus controlling renal proline excretion. It is possible that renal iminoglycinuric syndromes may not only be secondary to membrane transport disorders but may result from localized metabolic defects in the tubule cells.

ISSN:0031-3998    

出版商:OVID    

年代:1973

数据来源: OVID

摘要:

ExtractHigh levels of unconjugated estrone ((E1) 3-hydroxyestra-1,3,5(10)-triene-17-one) and estradiol ((E2) estra-1,3,5(10)-triene-3,17β-diol) were found at term in maternal venous, umbilical vein, and umbilical artery plasma. For estrone the respective values in nanograms per milliliter ±SD were 12.8 ± 5.9, 25.1 ± 6.5, and 13.2 ± 7.7. For estradiol the respective values were 17.3 ± 9.2, 8.1 ± 4.0, and 5.1 ± 3.2. For estrone, levels for umbilical vein were higher than those in the paired maternal and umbilical artery; estradiol was higher in maternal vein than in the paired umbilical vessels. Absence of the fetal adrenals was associated with low levels of estrone and estradiol for maternal and umbilical vessels, whereas, in anencephaly, only the maternal levels were markedly diminished. An initially rapid, and then a slower decline in both estrogens was found in normal infants during the first 72 hr of life.SpeculationDespite extensive metabolism of unconjugated estrogen by the fetus, umbilical arterial levels of estrone and estradiol are high. Nevertheless, the neonate shows scant clinical evidence of those high levels. This could be due to incomplete development of estrogen receptors in target tissues, plasma protein binding of estrogen, competition between the biologically most potent estrogen estradiol and the less potent estrone and estriol ((E3) estra-1,3,5(10)-triene-3,16α;,17β-triol), or other factors.

ISSN:0031-3998    

出版商:OVID    

年代:1973

数据来源: OVID

摘要:

ExtractProximal renal tubular acidosis has been observed in two infants who had lactic acidosis associated with subacute necrotizing encephalomyelitis. Reduced renal thresholds for bicarbonate (18–19.2 mM/liter) were found in both, in conjunction with the ability to excrete normal quantities of acid. In order to raise the level of serum bicarbonate, increasing rates of infusion of solutions containing bicarbonate were required, because of a progressive increase in serum lactate from 18 to 54 mg/dl. The infusion of sodium bicarbonate expanded the extracellular space, as measured by an increase in chloride space of 12.9%. Volume expansion was associated with a progressive fall in bicarbonate reabsorption from a maximum of 1.91 to 1.02 mM/100 ml glomerular filtration rate. In addition, the tubular reabsorption of phosphate fell from 80 to 60%, urate clearance increased from 8.7 to 20 ml/min/1.73 m2, lactate clearance increased from 0.23 to 22.9 ml/min/1.73 m2, and chloride excretion increased from 0.7 to 3.14 μEq/min/1.73 m2. At autopsy, reduced activity of renal pyruvate carboxylase was demonstrated for the first time in this disease.SpeculationAs a reflection of impaired lactate metabolism in subacute necrotizing encephalomyelitis (SNE), generation of ATP may be reduced in the renal cortex. This reduced supply of energy might be expected to impair reabsorption of normal quantities of filtered bicarbonate; proximal renal tubular acidosis may be the result. The fact that other evidence of proximal tubular dysfunction was not observed in the normohydrated state further suggests that failure to reabsorb filtered sodium bicarbonate may be the initial abnormality observed when the supply of energy diminishes in the renal cortex.The changes in the chloride space observed during bicarbonate infusions may provide data useful in the interpretation of changes in the renal threshold both for bicarbonate and for other solutes.Finally, it appears that subacute necrotizing encephalomyelitis may include a spectrum of biochemical abnormalities, and that only certain forms may be associated with renal tubular acidosis.

ISSN:0031-3998    

出版商:OVID    

年代:1973

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1973

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1973

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1973

数据来源: OVID