摘要:

ExtractAdditional lipids have been tested to determine whether they share with soya bean phospholipids (SBP) and dilinoleyl lecithin (DLL) the ability to sensitize the pregnant rabbit uterus to oxytocin, which permits the induction of premature labor at a time otherwise not possible. Comparable activity was given by none of the compounds tested intravenously but was given by methyl linoleate and methyl arachidonate administered by the intrauterine route, both at a dose of 1 g; abortion rates for these compounds were 69% ± 4.3% and 79% ± 7.8%, respectively. These values do not differ significantly from those for intravenous SBP and DLL.SpeculationAll highly active compounds thus far found have either linoleate or arachidonate as a part of their molecule. These essential fatty acids are precursors of prostaglandin E or F2α, both of which can stimulate myometrial contractions in the pregnant rabbit uterus and cause luteolysis. We postulate that active lipids act by conversion to prostaglandins, which in turn prepare the uterus for delivery. Both the time interval required to achieve this effect and the ability of progesterone to block it suggest that the prostaglandins act by luteolysis rather than by stimulation of myometrial contractions.

ISSN:0031-3998    

出版商:OVID    

年代:1974

数据来源: OVID

摘要:

ExtractWe have described a patient with ornithine transcarbamylase (OTC) deficiency. The clinical course and pedigree substantiate the X-linked transmission of the defect with varying degrees of illness in females. Because orotic aciduria accompanied hyperammonemia in the patient, orotic acid was measured as an indication of a partial OTG deficiency after ammonia and protein loading in members of the patient's family. Both the mother, an obligate carrier, and an aunt, the only symptomatic female in this pedigree, had hyperammonemia after the ingestion of ammonium chloride. They also had significant orotic aciduria after a protein load as did the two female cousins whose ammonium tolerance was normal. The maternal grandmother excreted a large amount of orotic acid in her urine relatively consistently. These data suggest that the two female cousins and the maternal grandmother are asymptomatic female heterozygotes despite their normal ammonium loading tests.SpeculationProtein loading in the form of a relatively palatable and innocuous meal, followed by determination of orotic acid content in urine, may prove to be a sensitive, noninvasive, and easy means to identify female carriers of ornithine transcarbamylase deficiency.

ISSN:0031-3998    

出版商:OVID    

年代:1974

数据来源: OVID

摘要:

ExtractExperimentally induced endotoxemia in the rhesus monkey produced a two- to fourfold increase in plasma triglyceride concentration; glucose administration partially prevented this rise. Plasma free fatty acid and phospholipid values were depressed 40–50% of control values whereas cholesterol values were unchanged. Endotoxin-treated monkeys displayed slowed glucose disappearance (K values, 2.2versus1.1) and higher levels of sugar in blood when given glucose (72 ± 8 mg/100 mlversus151 ± 11 mg/100 ml). These studies indicate that endotoxin has a marked effect on the pattern of substrate utilization by the host.SpeculationAlterations in lipid and carbohydrate metabolism affecting substrate utilization of the host may account for many of the clinicopathologic events associated with endotoxemia. Therapeutic measures designed to increase the availability of metabolic fuels for efficient cellular fuel utilization might be of value to patients during endotoxemia.

ISSN:0031-3998    

出版商:OVID    

年代:1974

数据来源: OVID

摘要:

ExtractA new variant of glucose phosphate isomerase (GPI) deficiency (type Nordhorn) associated with congenital nonspherocytic hemolytic anemia is described. The propositus, an 18-month-old boy of German origin, has suffered since birth from a severe to moderate macrocytic anemia, which is characterized by low mean corpuscular hemoglobin concentration (28%), high reticulocytosis (45—60%), normal osmotic fragility,type Iautohemolysis, and short erythrocyte life-span (51Cr t = 2 days). With the exception of GPI, the activities of most erythrocyte enzymes are increased. GPI activity is decreased to 22% of the normal. The father and mother exhibit GPI activities between 36% and 47% of normal. No difference is demonstrable between the enzyme of the propositus and normal subjects concerning Michaelis-Menten constant for fructose 6-phosphate, pH optimum, and thermal optimum. The stability of the enzyme is decreased in the propositus and in all affected maternal relatives. The enzyme of the paternal relatives is stable. On starch-gel electrophoresis the enzyme of the father is normal (three bands). In the hemolysate of the mother a fourth cathodally migrating band is demonstrable in addition to the three normal bands. The propositus exhibits only one band with a cathodal mobility of 132% of the main band of normal subjects. It is suggested that the propositus is double heterozygous for two abnormal alleles. The heterozygote mother contributes an allele which produces a thermolabile enzyme of decreased activity and abnormal electrophoretic mobility, whereas the father contributes an allele without enzymatic activity.The enzyme defect is also manifest in the leukocytes of the propositus (39% of normal activity). The thermolability is evident in the leukolysates of the propositus and in those of his mother.When erythrocyte glucose consumption and lactate formation are compared with nonenzymopenic, reticulocyte-rich blood, which has no metabolic defect, the rate of glycolysis is markedly impaired in the propositus. Glucose 6-phosphate, the substrate

ISSN:0031-3998    

出版商:OVID    

年代:1974

数据来源: OVID

摘要:

ExtractThe genetic variant of glucose phosphate isomerase (GPI) with hereditary nonspherocytic hemolytie anemia (GPI-Nordhorn) is purified 20,000-fold in a one-step procedure with a yield of 25%. A specific activity of about 100 IU per mg protein is obtained. The isoelectric point of the variant enzyme is 9.80, which is slightly higher than normal. The molecular weight is 94,000. Kinetic studies with the isolated enzyme gave results which are comparable to normal: Km(glucose 6-phosphate (G-6-P)) = 660 μM, Km(fructose 6-phosphate (F-6-P)) = 97 μM, Ki6-phosphogluconate (6-PG) (G-6-P) = 43 μM, Ki6-PG (F-6-P) = 19 μM, Ki2,3-diphosphoglycerate (2,3-DPG) ( F-6-P) = 850 μM, pH optimum (G-6-P) = 8.0, and pH optimum (F-6-P) = 8.5. It can be assumed that a genetically determined amino acid substitution causes the alteration of isoelectric point, electrophoretic migration, and increased thermolability but does not affect the active site of the enzyme.SpeculationBy the preparation of an enzyme variant reported herein a possibility is presented to obtain further structural characteristics by means of fingerprinting and amino acid analysis. It might be possible to correlate functional peculiarities to the altered structural properties of variant enzymes.

ISSN:0031-3998    

出版商:OVID    

年代:1974

数据来源: OVID

摘要:

ExtractTransient elevation of the activity of adenine phosphoribosyltransferase (APRT) was found along with hyperuricemia in an infant in the neonatal period. A systematic investigation was begun of the activity of the phosphoribosyltransferases in the first days of life. Adenine phosphoribosyltransferase and hypoxanthine guanine phosphoribosyltransferase (HGPRT) were assayed using radiochemical methods in which the nucleotide products of the enzymatic reactions are precipitated with lanthanum chloride. Phosphoribosyl pyrophosphate (PRPP) was assayed using a method based on the utilization of PRPP in a system containing (14C)adenine and APRT. The activity of APRT in the neonate was found to exceed consistently that of the adult. The degree of elevation was as great as that observed in patients with Lesch-Nyhan syndrome. The mean value of APRT in the adult was 665 nmol AMP/min/ml packed cells, whereas in the neonate the mean value was 1,150. The difference between neonate and adult was significant statistically at the <0.001 level.Erythrocytes of adults were fractionated into young and old cells. The activity of APRT in the young cells from each individual was 1.5–2.1 times that of the old cells. The concentrations of PRPP were significantly greater in the erythrocytes of neonates than in those of adults (P< 0.001). The mean concentration in the infants was 2.4 times the adult mean value.It was concluded that the elevated activity of APRT in the neonate reflected partly a young population of cells and partly a stabilization by PRPP of APRT against the attrition of aging.SpeculationThe activity of APRT was first found to be elevated in the erythrocytes of patients with the Lesch-Nyhan syndrome. It has been found to be elevated to an identical degree in patients with partial deficiency of HGPRT and with overproduction of uric acid without abnormality in HGPRT. Now it is apparent that APRT is elevated to precisely the same degree in the normal newborn infant. These observations speak for a common mechanism of biologic control.

ISSN:0031-3998    

出版商:OVID    

年代:1974

数据来源: OVID

摘要:

ExtractIn human fetal liver cultures addition of glucagon or dibutyryl adenosine 3',5'-monophosphate (dibutyryl cyclic AMP) plus prednisolone to the medium for 24 hr evokes an increase in tyrosine α-ketoglutarate transaminase (TTA) activity which is much greater than the sum of the rises due to glucagon, dibutyryl cyclic AMP, or prednisolone alone. This effect is time (24 hr of incubation) and age (the largest effect in the oldest fetus) dependent. This synergistic effect is not seen with phosphoenolpyruvate carboxykinase (PEPK). Glucagon alone or norepinephrine alone has only a very dubious effect on TTA but both hormones raise PEPK activity by about 60% in culture.Alanine and aspartate transaminases are not affected by any of the inducers tested, but both increase in activity during culturing.SpeculationTheoretically, it is possible that injections of steroids to pregnant mothers together with higher than normal levels of dibutyryl cyclic AMP in fetal liver can cause large increases in fetal hepatic tyrosine transaminase. The metabolic consequences of such a rise for the fetus are completely unknown. It is not even known whether such a rise would be permanent or transient. In view of our ignorance, we should be hesitant about treating pregnant women with steroid drugs.

ISSN:0031-3998    

出版商:OVID    

年代:1974

数据来源: OVID

摘要:

ExtractElevated levels of saecharopine, lysine, and citrulline in urine and plasma were observed in a patient suffering from saccharopinuria. Using radioisotope methods the lysine-degradative enzymes, lysine-oxoglutarate reductase and saecharopine dehyrogenase, were studied in skin fibroblasts grown from this patient and from healthy subjects.The results show that, in contrast to healthy individuals (range 177–320 pmol formed/min/mg protein), the paitent's fibroblasts are completely lacking in saecharopine dehydrogenase activity, which accounts for the presence of the high levels of saccharopine. The patient also has a reduced level of lysine-oxoglutarate reductase activity (333 pmol saccharopine formed/min/mg protein; range 550–1,570 nmol), which may in part explain the hyperlysinemia. A further enzyme saecharopine oxidoreductase which metabolizes saecharopine to lysine was found to be present in the patient's fibroblasts (63 pmol lysine formed/min/mg protein) but absent from those of healthy control subjects. This indicated induction of this enzyme by the patient in an attempt to reduce the high levels of saecharopine in her tissues and body fluid.SpeculationThere are two interesting features of this patient with saccharopinuria which the present studies have not clearly defined, namely the presence of high levels of lysine and citrulline found in plasma and urine.There are three possible explanations for the hyperlysinemia which may be operating singly or in combination. Depression in activity of lysine-oxoglutarate reductase (the patient possesses 37% of the normal activity). Inhibitory effect of saecharopine on lysine-oxoglutarate reductase (in vitrostudies). Induction by the patient of saccharopine oxidoreductase which metabolizes saccharopine to lysine.No explanation has yet been found for the high levels of citrulline in plasma and urine.

ISSN:0031-3998    

出版商:OVID    

年代:1974

数据来源: OVID

摘要:

ExtractCerebral blood flow (CBF) with the133Xe clearance technique and cerebral oxygen consumption were measured in the fetal lamb using chioralose-anesthetized ewes and acutely exteriorized fetuses with intact umbilical circulation. To induce fetal hypoxia at different pH levels, three different procedures were used: (1) the ewe was ventilated with a hypoxic gas mixture, containing 8–15% O2in N2; (2) 5–10% CO2was added to the hypoxia gas mixture; (3) during hypoxia a continuous rapid infusion of NaHCO3solution was given intravenously to the fetus. Blood gas tensions, pH, and oxygen saturation were measured repeatedly.Multiple regression analysis was carried out on the data with the variables SaO2, PaO, PaO2, and pH considered as independent variables and flow as the dependent variable. All complete sets of observations were used amounting to 74 observations in 11 animals. No significant correlation was found between CBF and pH. SaO2showed the highest correlation to CBF. No further improvement of this correlation was obtained when PaCO2was added as independent variable. PaO2and PaCO2described jointly the variations of CBF as well as SaO2alone.The oxygen consumption of the brain decreased during hypoxia when SaO2was reduced below 40%. The decrease of the metabolic rate for oxygen was a function both of the degree of hypoxia and of pH. When an acidosis was added to the hypoxia a significant reduction of the oxygen consumption of the brain resulted compared with the same degree of hypoxia at normal or only moderately reduced pH levels.SpeculationThe cerebral blood flow of the fetal lamb is regulated mainly via the amount of oxygen available to the brain, and changes of CO2tension affect CBF via a displacement of the hemoglobin dissociation curve.Cerebral oxygen consumption is reduced to dangerously low levels when a severe acidosis is combined with hypoxia because of a failure to extract the oxygen available in the arterial blood.

ISSN:0031-3998    

出版商:OVID    

年代:1974

数据来源: OVID

摘要:

ExtractSomatosensory evoked electroencephalogram (EEG) responses (SER) were recorded in 19 fetal lambs with gestational ages varying from 66 to 140 days. The ewes were anesthetized with chloralose and the fetuses were exteriorized with intact umbilical circulation. Periods of hypoxia at different pH levels were induced by ventilating the ewe with gas mixtures including 8–15% oxygen, either alone or combined with a 10% CO2mixture, or with an intravenous infusion of bicarbonate to the fetus.The reaction of the SER during hypoxia followed two main patterns, one seen in the immature fetus and one in the more mature fetus. In the immature type of response (seen in all fetuses at or less than 110 days of gestational age) the primary response of the SER is more sensitive to oxygen lack than the secondary components, whereas in the mature type of response (seen at or more than 115 days of gestational age) the reverse is true.At moderate degrees of hypoxia, PaO2between 15 and 20 mm Hg, the SER were moderately affected provided that the pH of the blood was within normal limits. At lower PaO2, values, and when moderate hypoxia was combined with acidosis, the SER were seriously affected or completely abolished. At PaO2, values above 20 mm Hg an acidosis had no effect on the SER.SpeculationThe function of the fetal brain is seriously jeopardized by the combination of hypoxia and acidosis. Therefore, both hypoxia and acidosis should be counteracted during asphyxia to prevent brain damage.

ISSN:0031-3998    

出版商:OVID    

年代:1974

数据来源: OVID