摘要:

ExtractThe fetal hemoglobin of 10 infants has been examined serially from birth to several hundred days of age. In the normal child, the ratio ofG&ggr; toA&ggr; chain alters from about 7:3 at birth to about 2:3 at 150‐200 days. In children with abnormalities of hemoglobin synthesis, the ratio changes as expected from data from adults with the particular abnormality. Thus, little change in ratio was shown by two &bgr;‐thalassemia homozygotes, whereas two &bgr;‐thalassemia heterozygotes showed the same behavior as a normal child; the latter behavior is expected from one of the two classes of &bgr;‐thalassemia heterozygotes. A heterozygote from theG&ggr;A&ggr; class of hereditary persistence of fetal hemoglobin behaved much like a normal child, but two heterozygotes from theG&ggr; class showed the expected change from approximately 9:1 at birth to 10:0 postnatally. Two children with sickle cell anemia resembled a normal child in change of ratio whereas the third, not unexpectedly, did not show a change in ratio.SpeculationThe mechanisms involved in the gradual change from &ggr; chain synthesis to &bgr; and &dgr; chain synthesis are complex and ill defined. The results of analyses of the ratio between the products of theG&ggr; andA&ggr; structural genes in infants with distinct genetic disorders at birth and during the postnatal period underscore the complexity of the changeover. However, differences in the postnatal change in theG&ggr; toA&ggr; ratio in infants with an apparent identical condition may help to further define these mechanisms, and to delineate the conditions involved.

ISSN:0031-3998    

出版商:OVID    

年代:1975

数据来源: OVID

摘要:

ExtractA premature infant with jaundice was found to have a compensated hemolytic process as evidenced by mild hyperbilirubinemia, a regenerative anemia, and persistence for several months of reticulocytosis, polychromatophilia, and stippled macrocytes. There was no blood loss. When hemoglobins from this family were electrophoresed, the propositus and her mother were found to be heterozygous for an abnormal hemoglobin. The variant hemoglobin, which was 20% of the mother's hemoglobin, had the electrophoretic mobility of hemoglobin S; however, sickle preparations were negative at 24 hr and, in contrast to hemoglobin S, the hemoglobin was soluble in 2.58 M phosphate buffer. The mother's pattern also revealed a faint band running behind A2and very close to the origin. The distance between this variant and A2was about the same as the distance between the major variant and A. Such a pattern suggested that the hemoglobin mutation was in the &agr; chain. Examination of the infant's electrophoretic pattern revealed a third variant hemoglobin whose distance from fetal hemoglobin was the same as the distances of the variants in the mother's pattern, which indicated that an abnormal fetal hemoglobin was present. By 7 months of age the infant's electrophoretic pattern was identical with that of her mother and the variant hemoglobin accounted for about 20% of the total.Since the propositus was a premature infant, structural studies were carried out on the adult variant which was isolated chromatographically from the mother's blood. Analysis of the tryptic peptide chromatogram of the &agr; chain revealed that peptide T‐6 was absent; a new peptide was isolated at a lower position on the chromatogram. The amino acid composition of this peptide revealed that the aspartic acid atposition 47was replaced by histidine. Therefore, the mutant hemoglobin was hemoglobin Hasharon (&agr;‐47 (CD5) aspartic acid → histidine).Chromatographically prepared hemoglobin F was hybridized with a similar preparation of the adult hemoglobin Hasharon. After electrophoresis, we found bands corresponding to hemoglobin A and to the fetal hemoglobin Hasharon, as well as the original hemoglobin F and adult hemoglobin Hasharon. There were also two bands which migrated anodal to hemoglobin A which might have been hemoglobin H and hemoglobin Bart's, representing tetramers of the normal &bgr; and &ggr; chains. These tetramers may have formed because of the relative instability of the mutant &agr; chains.SpeculationThe marked hemolytic process in this premature infant was dependent on the presence of the fetal form of hemoglobin Hasharon in fetal erythrocytes. Hemolysis resolved as these cells were replaced by adult‐type erythrocytes which contained the adult form of hemoglobin Hasharon.

ISSN:0031-3998    

出版商:OVID    

年代:1975

数据来源: OVID

摘要:

ExtractIn 8 of 10 patients with pseudohypoparathyroidism, confirmed by increased immunoreactive plasma parathyroid hormone concentrations and/or defective urinary excretion of adenosine 3',5'‐monophosphate (cAMP) after parathyroid extract infusion, excessive plasma thyrotropin (thyroid‐stimulating hormone) (TSH) response to thyrotropin‐releasing hormone (TRH) injection was found. On the other hand, in all seven cases with idiopathic true hypoparathyroidism the TSH response was normal. In two of three patients with pseudopseudohypoparathyroidism, with normal or slightly low plasma calcium, normal or slightly high immunoreactive plasma parathyroid hormone concentration, and intermediate response of cAMP to parathyroid extract, the TSH response to TRH was increased. The results indicate that moderate primary hypothyroidism is frequently present in pseudohypoparathyroidism. Thyroid dysfunction may only be detectable with the use of TSH stimulation by TRH, since clinical signs and other studies of thyroid function did not definitely suggest hypothyroidism in our patients. The rise of TSH is suppressible by thyroxine treatment, but is not influenced by vitamin D treatment. The TSH response to TRH is significantly correlated with the decrease of tubular reabsorption of phosphate after parathyroid extract infusion in patients with pseudo‐ and pseudopseudohypoparathyroidism.SpeculationTSH stimulation by TRH may be a useful test for the further delineation of biochemical variants of pseudohypoparathyroidism.

ISSN:0031-3998    

出版商:OVID    

年代:1975

数据来源: OVID

摘要:

ExtractThe secretion of insulinin vivoand its synthesis and release by pancreatic isletsin vitrowere studied in rats at various stages of development. An oral glucose load caused a rapid and significant increase in the serum insulin level of pregnant rats and a slower response in their 21‐day‐old fetuses. Circulating free fatty acids (FFA) decreased in the dams, but did not change in the fetuses. A relative glucose intolerance was found in pups 1 hr, 5 days, and 10 days after birth. This was accompanied by delayed insulin response and by little or no decrease of circulating FFA. After weaning, the glucose tolerance and the insulin and FFA responses gradually improved. The oral administration of a 10‐amino acid mixture caused a greater insulin release in newborn and nursing rats than in 21‐day‐old fetuses or in young adult rats. Total serum lipids were higher in 1‐, 5‐, 10‐, and 20‐day‐old rats than in fetuses and adult animals, whether fed or fasted, but 18 hr of fasting decreased total lipids and phospholipids in all age groups. Thus, the age of relative hyperlipidemia corresponded with that of relative glucose intolerance. The secretion of insulinin vitroby pancreatic islets of 5‐, 10‐, 20‐, 30‐, and 45‐day‐old rats increased significantly when the concentration of glucose in the incubation medium was increased from 30 to 300 mg/ml. The islets of 30‐ and 45‐day‐old rats secreted the largest amount of insulin. The insulin content of pancreatic islets was higher and the percentage of insulin secreted in relation to the hormonal content was smaller in the islets of nursing rats. Islets of fetal, nursing, and adult rats incorporated L‐[4,5‐3H] leucine into proinsulin and insulin, but the conversion of proinsulin to insulin was minimal in the 1‐day‐old rat. This incorporation was greater when the glucose concentration of the medium or the incubation time were increased. Thus, birth appears to be associated with a temporary decrease in the ability to release insulin and to dispose of an exogenous glucose load.SpeculationBirth deprives the newborn pup of transplacental nutrition and exposes it to the danger of neonatal hypoglycemia, especially in the interval between birth and the first act of nursing. This danger is moderated by a previously described increase in the serum level of glucagon and by a decrease in the serum level of insulin. This change in the glucagon to insulin ratio favors hepatic glycogenolysis and gluconeogenesis and, possibly aided by the relative hyperlipidemia characteristic of this age, decreases the utilization of glucose by the relatively large masses of insulin‐responsive tissues. Gluconeogenesis continues to be a major source of glucose throughout the nursing age, when the animal consumes a diet rich in protein and fat and low in carbohydrate. Although the fetal pancreas can synthesize insulin, the mechanism for its release and hence the ability to dispose of a glucose load do not reach full maturity until weaning, when the dietary intake of carbohydrate increases and the level of serum lipids decreases toward the values characteristic of the adult animal.

ISSN:0031-3998    

出版商:OVID    

年代:1975

数据来源: OVID

摘要:

ExtractThe binding of diphenylhydantoin (DPH) to plasma proteins was studied with an equilibrium dialysis method in plasmas in which concentrations of free fatty acids (FFA) were varied by physiologic means. In blood‐perfused dog subcutaneous adipose tissue, sympathetic nerve stimulation caused an increase in plasma FFA concentration from control values of 0.26‐0.58 mM to peak levels of 0.63 to 3.44 mM. There was a linear relation between the binding of DPH and the FFA concentration in plasma from the same dog. When rat epididymal adipose tissue was incubated in dog plasma containing DPH, DPH protein binding decreased and tissue binding of the drug increased with increasing lipolytic rate. In plasma from 42 newborn infants the degree of DPH binding was significantly related to the albumin concentration as well as the bilirubin to albumin and FFA to albumin concentration ratios.SpeculationOur data indicate that physiologically occurring variations in plasma FFA concentration can alter the plasma protein binding of drugs. We propose that such displacement will be quantitatively most important in blood perfusing adipose tissue during lipolysis and that the effect might lead to a preferential distribution of the drug to fat tissue during lipolysis.

ISSN:0031-3998    

出版商:OVID    

年代:1975

数据来源: OVID

摘要:

ExtractEmbryonic mumps virus infection in the avian host leads to fetal growth retardation. The mechanism of this retardation has not been established.The avian host is unique in that the direct effect of a virus on the embryo may be ascertained in the absence of a placenta.Using radioisotope labeling techniques, DNA, RNA, and protein metabolism was investigated in tissues from infected and control chickens. Metabolism in organ tissue cultivatedin vitroand then infected was also studied using the same radioisotope techniques.At hatch, the mean body weight of eight experimental chickens infected with mumps virus early during embryonic incubation was significantly less than that of 19 controls. This lower weight was evident in the brain of the infected chickens. The brain and carcass contained decreased amounts of RNA and protein when compared with uninfected control chickens. The kidney was the only other organ in which the protein content in experimental chickens was less than in controls.There was no difference in the DNA content of organs fromin ovo‐infected and control chickens or organ tissues cultivatedin vitrobefore infection with mumps virus. Similarly, measurements of cell number at the same time were equal.Viral assay of the chickens infectedin ovorevealed highest titers of virus in the heart throughout the last half of incubation. Intermediate titers of virus were recovered from the lung, spleen, and skeletal muscle. Low quantities of virus were recovered from the brain and liver. The bursa contained high titers of virus at midincubation but these titers rapidly declined by hatch.Growth retardation in the mumps virus‐infected chicken model is not due to a reduction in cell number but appears to be caused by a diminution in cell size.SpeculationThe relation between embryonic mumps virus infection and myocarditis is supported by the findings of high titers of virus throughout the incubation period. It is postulated that altered cardiac function results in a state of hypofusion and a preferential effect is seen in the brain with consequent diminution of cell size rather than cell number.

ISSN:0031-3998    

出版商:OVID    

年代:1975

数据来源: OVID

摘要:

ExtractData on serum immunoreactive insulin (IRI), glucose tolerance, serum growth hormone (HGH), and amino acid levels obtained during previous studies of 35 children suffering from protein‐calorie malnutrition (PCM) have been reviewed. In all children intravenous glucose tolerance tests (1 g/kg glucose) were performed after 24 hr of carbohydrate feeding and before protein was introduced into the diets. In 19 of the 35 cases the tests were repeated 24‐72 hr after either an albumin or amino acid infusion or milk feeding, and in 29 after 3‐6 weeks of refeeding.It was found that the IRI response to glucose paralleled the severity of malnutrition, being low on admission, and improving with recovery. There was a correlation between peak IRI response and both serum albumin and serum alanine levels on admission, but acutely induced increase of albumin and infusions of alanine containing amino acids during therapy did not result in a consistent improvement of insulin secretion. Correlation between peak IRI and the branch chain amino acids barely reached significance on admission. There did not appear to be a direct relation between IRI peak or area and either basal HGH levels or the degree of HGH suppressibility.The glucose intolerance appeared to be related to the poor insulin response, although there were numerous exceptions which indicated that factors other than those recorded in this study are likely to be involved in the production of the glucose intolerance of PCM.SpeculationThe impaired insulin response to glucose characteristic of PCM is associated with severe protein depletion. It is unlikely that the insulin deficiency or the glucose intolerance are related to a single abnormality; they are more likely part of widespread metabolic disturbance or adaptation which varies in importance in each individual.

ISSN:0031-3998    

出版商:OVID    

年代:1975

数据来源: OVID

摘要:

ExtractThe binding of cortisol to plasma proteins was studied by a methodology allowing the determination of the apparent affinity constant (Ka) and the specific binding capacity (Ns) for transcortin in different blood compartments in normal pregnant women at term, in the umbilical cord blood, and in normal neonates and infants throughout the first year of life. Removal of endogenous steroids appeared to be necessary for these binding studies, especially in the cord plasma. Both an equilibrium dialysis and an adsorbent technique were used, inasmuch as it has been established that they yield similar results for corticosteroid‐binding globulin (CBG) binding parameters.The high affinity binding of cortisol, attributed to transcortin, was found to have the highest capacity in plasma from pregnant subjects (Ns= 1.16 ± 0.19 × 10−6M), whereas the fetal compartment (umbilical cord) exhibited low values (0.25 ± 0.03 × 10−6M). Thus a physiologic barrier to the transplacental passage of transcortin resulted in a large concentration gradient in cortisol‐specific binding sites between the fetal and maternal compartments. No significant differences were found for transcortin capacity between venous uterine plasma and peripheral plasma in three subjects studied during cesarean section. A possible physicochemical difference between maternal and fetal transcortin appeared unlikely, because in all blood compartments studied, the apparent affinity constant, Ka, was similar (5‐8 × 108M‐1at 4°), and the behavior of the specific cortisol binder in polyacrylamide gel electrophoresis was the same in all cases.After birth, although the transcortin Kafor cortisol was still in the same range, Nsremained low during the first month of life (0.23 ± 0.07 × 10−6M); after which an increase toward normal adult values was seen, with a rather large variation between individuals from 2‐12 months of age (mean 0.48 ± 0.10 × 10−6M). Children above 1 year exhibited adult values for Ns(0.51 ± 0.03 × 10−6M).SpeculationFrom the similarity of values found for transcortin Kaand electrophoretic behavior, the physicochemical properties of the glycoprotein cortisol binder are likely to be the same both in the maternal and fetal compartments, although final evidence of chemical identity is not available. Thus, the different binding capacity between these compartments might be attributed to a different concentration in circulating transcortin. This concentration gradient may play a role in the transplacental transfer of corticosteroids during pregnancy and would favor passage toward the maternal compartment. The low transcortin level in the neonatal period might be attributed to a low biosynthesis capacity of the liver in the neonate, although nothing is known about the clearance rate of transcortin in the neonatal period. The transcortin level increases toward adult values during the first year of life and this would suggest either a maturation of the liver biosynthesis enzymatic systems or a biosynthesis stimulation. A possible contribution of a pituitary factor might be suggested on the basis of experimental work in the rat, but the meaning of this increase in cortisol binding capacity in plasma remains to be elucidated.

ISSN:0031-3998    

出版商:OVID    

年代:1975

数据来源: OVID

摘要:

ExtractIn order to determine whether the mechanical characteristics of the lungs of newborn infants imposed limitations on their ventilatory response to carbon dioxide, 11 premature and 5 full term infants ranging in gestational ages from 28‐40 weeks and in birth weights from 964 to 4,040 g were studied by a rebreathing technique. Sensitivity to carbon dioxide determined by this method revealed a good correlation with compliance (r = 0.6,P< 0.001), and an even stronger correlation with gestational age (r = 0.84,P< 0.001). Because compliance also improved with increasing postconceptional age, the current study does not permit one to differentiate between neurologic or pulmonary mechanical factors which may affect ventilatory response to carbon dioxide.SpeculationInfants who respond to carbon dioxide with an increase in minute ventilation should also increase their rate of pulmonary work. Failure of this work rate to increase in response to elevated carbon dioxide tensions may indicate that nonresponsive infants are already working at their maximum level of pulmonary work, and would thus permit differentiation of infants who have mechanical limitations to increased performance as opposed to those who lack chemoreflexes.

ISSN:0031-3998    

出版商:OVID    

年代:1975

数据来源: OVID

摘要:

ExtractAtkinson's metabolic price system has been applied to the calculation of the energy costs of growth of a 3‐week‐old, 3,900‐g “male reference baby,” growing along the 50th percentile. The increase in weight of liver, brain, lung, spleen, and kidney has been calculated from literature data. The other organs and tissues were assumed to grow proportionally to the gain in body weight corrected for the weight gain of the organs mentioned above. The gross chemical composition of tissues and organs has been used to calculate the increases in specific tissue components, such as proteins, triglycerides, phospholipids, cholesterol, glycogen, DNA, and RNA. Of the total weight gain of 6.9 g/kg body wt/24 hr, 25.2% could be accounted for as solids deposited in the body, the remainder, 74.8%, being water. The energy needed to synthesize these solids has been calculated in terms of ATP equivalents, ATP being the form of energy used in the biochemical synthetic reactions. A total of 0.0614 mol ATP Eq is needed/kg body wt/24 hr in addition to 0.164 g glucose/kg body wt/24 hr. Proteins, which accumulate at a rate of 0.971 g/kg body wt/24 hr, take 87.7% of these ATP Eq. The energy needs for the active uptake of ions has also been calculated and was found to be 0.0108 mol ATP Eq/kg body wt/24 hr, which increases the total to 0.0722 mol ATP Eq kg body wt/24 hr.These ATP equivalents can be generated by the complete oxidation of 0.342 g glucose, which sets the total energy need to maintain growth at 0.506 g glucose/kg body wt/24 hr. Assuming an intake of humanized milk containing 69 kcal/100 ml, at 140 ml/kg body wt/24 hr, 2.2% of the total caloric intake is needed to cover the energy cost of normal growth.SpeculationThe metabolic price system theory as developed by Atkinson may prove to be very useful in calculating the energy requirements for specific functions, such as performance of mechanical work, maintenance of ionic equilibrium, and energy costs for replacing body constituents, as more becomes known about the stoichiometry of biochemical reactions in various organs.

ISSN:0031-3998    

出版商:OVID    

年代:1975

数据来源: OVID