摘要:

IGF-I, IGF-II, and their binding proteins (BP) were studied in sera obtained by direct puncture of umbilical cordsin uterobetween 20 and 37 wk of gestation in 103 normal fetuses and in 16 fetuses with intrauterine growth retardation, as well as in the cord blood of 37 normal newborns of 38− to 42-wk pregnancies. In normal fetuses, IGF-I levels were approximately 50 ng/mL and IGF-II levels approximately 350 ng/mL up to the 33rd wk of pregnancy. Thereafter, both increased to reach values two to three times higher at term. Correlations were found between fetal placental lactogen levels and those of IGF-I and IGF-II, which is consistent with the hypothesis that placental lactogen is involved in the regulation of IGF synthesis in the fetus. With weight (either measured at birth or deduced from echographical data) as index of fetal size, IGF-I levels were significantly (p< 0.001) higher in fetuses with weights above the mean for gestational age than in fetuses with weights below the mean, whereas IGF-II levels were similar in the two groups. Similarly, IGF-I (but not IGF-II) levels in fetuses with intrauterine growth retardation were significantly lower than those in normal fetuses of the same age (p< 0.01). These findings suggest that, during the latter months of intrauterine life, IGF-I (but not IGF-II) is involved in the control of fetal size. Total fetal BP concentrations were approximately 1/3 those of adults. The fetal electrophoretic profile obtained by Western-ligand blotting bore a strong resemblance to that of subjects with growth hormone deficiency. In new borns, the proportions of IGF-I and IGF-II associated with BP to form 150-kD complexes were considerably lower than those in adults, but similar to those in hypopituitary patients. It may be deduced from these findings that during fetal life, BP synthesis is adapted to increase the bioavailability of the IGF at a time when growth is at a maximum.

ISSN:0031-3998    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

We studied the pre- and postnatal developmental regulation of the hepatic type I IGF receptor in the rat. Fetal rat liver membranes bound IGF-I throughout the latter part of gestation (d 17 to 21). After birth, binding diminished rapidly, reaching barely detectable levels by the 13th postnatal d. However, the presence of type I IGF receptors was readily demonstrated by affinity-labeling throughout the immediate postnatal period and in adult rats. Furthermore, IGF-I-dependent autophosphorylation of type I receptors could be seen in both fetal and adult liver membranes. Fasting for 48 h in adult rats led to a 2-to 3-fold increase in affinity-labeled type I IGF receptors. In contrast, nutrient deprivation to the fetus, via maternal fasting, did not alter fetal hepatic IGF-I binding or affinity-labeling of the type I receptor. These results support a role for the IGF and the type I IGF receptor in the autocrine/ paracrine regulation of hepatic growth through the latter stages of gestation in the rat. The demonstration of enzy-matically active type I IGF receptors in adult liver, and their increased expression in fasted adult rats is consistent with an autocrine/paracrine role for hepatic IGF-I in the adult. (Pediatr Res 29: 226–230, 1991)

ISSN:0031-3998    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Vagal responsivity to orogastric stimulation is necessary for gastrointestinal function and may reflect antonomic regulation. Our study evaluated vagal responsivity during gavage feeding as an index of preterm clinical status. Vagal and behavioral responsivity of 26 preterm infants during gavage feeding was measured. Vagal tone was quantified with a noninvasive measure (vagal tone index) developed by Porges (Porges SW: U.S. patent 4 510 944, 1985), which extracts a valid measure of cardiac vagal tone from the ECG. The study investigated whether vagal tone changed during gavage feeding and whether individual differences in the vagal tone response pattern were related to clinical outcome. Infants who demonstrated an increase in vagal tone during feeding and a decrease after feeding had significantly shorter hospitalizations. This effect was independent of weight gain trajectories. Baseline levels of vagal tone were positively associated with subsequent weight gain. Traditional risk measures did not predict length of hospitalization independently of gestational age. This study represents the first documentation that small changes in cardiac vagal tone during gavage feeding, previously imperceptible to clinicians and researchers, may be quantitatively extracted from the ECG and provide an important index of clinical status. (Pediatr Res 29: 231–236, 1991)

ISSN:0031-3998    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The lamina propria (LP) contains many lymphocytes that are effector cells as well as memory cells of the gut immune system. This compartment was studied in normal and germ-free pigs in the early postnatal period up to 91 d of age. The number of LP lymphocytes nearly doubled between the 1st and 29th d. LP lymphocytes proliferated more in the crypt region than in the villi with a mitotic rate/h comparable to that in nonfollicular compartments of Peyer's patches and lymph nodes. The determination of the subpopulations of LP lymphocytes showed a 10-fold increase in CD22cells between d 1 and 40. About 80% of the LP T cells in 1− and 5-d-old pigs had the unusual CD2+CD4–CD8–phenotype. Ig-positive cells appeared later in the postnatal period than the T cells. On d 1, only a few IgM+cells were observed. In 40-d-old animals, the number of IgA+cells exceeded that of IgM+. Ten times more Ig+cells were detected in the crypt region than in the villi. The germ-free pigs at an age of 49 d had a T cell subset pattern comparable to that of 5-d-old normal animals. (Pediatr Res 29: 237–242, 1991)

ISSN:0031-3998    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The origin of intact (78-kD) lactoferrin found in the urine of human milk-fed preterm infants was investigated using human milk containing proteins enriched with [13C]leucine and [15N2]lysine or [2H4]lysine. Mothers of infants selected for the study were infused i.v. with [13C]leucine and [15N2]lysine or [2H4]lysine to label milk proteins. The labeled milk was collected from each mother, pooled, fortified with a lyophilized human milk fraction, and fed to her preterm infant by continuous orogastric infusion for a period of 48 h. Urine was collected from each infant for 96 h. Intact lactoferrin (78 kD) and DNA-bioding lactoferrin fragments (51 and 39 kD) were purified from the urine by affinity chromatography on columns of immobilized single-stranded DNA-agarose. The concentration and isotopic enrichment of the intact lactoferrin and DNA-binding fragments were determined separately after their isolation by high-performance reverse-phase (phenyl) chromatgraphy. Mass spectral analyses indicated that the isotopic enrichment of the purified urinary lactoferrin was 87 to 100% of that in the labeled human milk lactoferrin. Similar results were obtained for the isolated DNA-binding lactoferrin fragments. The ratios of isotopically labeled leucine to lysine in the purified milk lactoferrins and urinary lactoferrins were similar for each mother/infant pair. Isotopically labeled lysine, added to the milk as free amino acid, was not incorporated into the purified urinary lactoferrin. These results demonstrate that undegraded (78-kD) lactoferrin of maternal origin is absorbed by the gut and excreted intact in the urine of preterm infants; nearly all of the urinary lactoferrin was of maternal origin. The possible immunoregulatory functions of the absorbed intact, maternal lactoferrin are discussed. (Pediatr Res 29: 243–250, 1991

ISSN:0031-3998    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

We studied the effect of human milk on DNA synthesis of neonatal hepatocytes to elucidate the physiologic role of human milk in growth of the liver. Neonatal hepatocytes were isolated from 5-d-old rats and cultured in serum-free medium. Human milk stimulated DNA synthesis of these hepatocytes in a concentration-dependent manner. The stimulatory activity of 7.5% (vol/vol) human milk plus 0.1 $mUmol/L insulin was five times that of control and was almost the same as that of 20 $mUg/L human epidermal growth factor (hEGF) plus insulin. The effect of human milk was additive with treatment with hEGF and insulin. The milk associated with prolonged jaundice of infants was significantly more active than the milk that was not associated with jaundice, although the concentration of hEGF was not different between the two types of milk. The mitogenic activity of milk was heat-labile, inactivated by DTT and stable after treatment with trypsin. Three peaks of the activity were detected in milk by gel filtration and the fraction containing proteins of molecular weight between 36 000 and 76 000 showed the highest activity. Anti-hEGF antibody did not inhibit this activity completely. These results suggested the presence of mitogens other than hEGF or a more active form of hEGF in human milk. The milk associated with breast-milk jaundice exerts a different influence on cell growth and may affect maturation of the liver function related to bilirubin metabolism. The mitogenic activity of milk might be important for growth and development of the liver in infants. (Pediatr Res 29: 251–255, 1991)

ISSN:0031-3998    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

To study the effects of peroxisome proliferators on fetal biogenesis, 400 mg/kg oral clofibrate was administered to pregnant mice beginning at d 6 of gestation. Maternal/fetal tissues from three separate experiments were harvested between gestational d 13 and 19 and maternal/fetal tissues were assayed for peroxisomal matrix, membrane-associated, and integral membrane proteins. By comparison to control pregnancies that received vehicle only, clofibrate produced a 4− to 5-fold increase in the levels of peroxisomal membrane protein 70, a 1.5− to 2-fold increase of dihydroxyacetone phosphate acyltransferase (DHAP-AT) sp act, and a 1.2− to 1.8-fold increase of catalase sp act in fetal liver of 19 d gestation. Fetal liver endoplasmic reticulum and peroxisomes were also amplified as visualized by electron microscopy. Clofibrate exhibited maximal effects on maternal tissues by 6 d of oral treatment with increases in peroxisomal membrane protein 70 occurring most clearly in maternal liver; DHAP-AT activity was increased in maternal liver, kidney, and brain but not in lung. Slight increases in DHAP-AT activities were evident in fetal brain, lung, and placenta as compared with the greater increases in liver and kidney. There was a general increase in peroxisomal proteins between 13 and 19 gestational d in all fetal tissues except placenta, and the effect of clofibrate was evident by gestational d 13 in lung and placenta. Minimal changes in the activities of acid phosphatase (lysosomal enzyme) or glycerol-3-phosphate acyltransferase (microsomal enzyme) were observed in maternal or fetal tissues although the latter enzyme was increased 10–30% by clofibrate in maternal brain, fetal lung, and placenta. The degree of amplification peroxisomal membrane portion 70 > DHAP-AT > catalase observed in several tissues after clofibrate treatment is consistent with a similar order in the sequence of peroxisomal assembly. The ability to manipulate fetal peroxisomes by maternal pharmacology provides a potentially useful system for studying the regulation of peroxisomal biogenesis. (Pediatr Res 29: 256–262, 1991)

ISSN:0031-3998    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Kidney epithelial cells in short-term primary culture have been studied with regard to proliferative rate and expression on thec-fosprotooncogene. The experiments were performed on subconfluent renal proximal tubule cells isolated from infant and adolescent rats. Proliferation was determined by3H-thymidine autoradiography and nuclear content ofc-fosprotein by semiquantitative immunofluorescence. The basal proliferative rates in infant and adolescent renal proximal tubule cells were the same after 48 h of primary culture in Dulbecco's modified Eagle's medium with 10% FCS. Serum deprivation for 24 h caused a significant growth inhibition in both infant and adolescent cells. C-foswas expressed to the same extent in infant and adolescent serum-deprived cells. The rapid response to the addition of serum was markedly different in infant and adolescent cells. In adolescent cells, addition of serum led to a transient significant increase in the nuclear expression ofc-fosprotein, reaching a peak at 60 rain. No increase hic-foswas seen in infant cells. In adolescent cells, the rate of proliferation increased 11-fold and3H-thymidine labeling index reached 26.7 $$ 4.3%. In infant cells, the proliferative response to serum addition was significantly lower; the labeling index reached only 4.2 $$ 1.2%. It could be excluded that the attenuated response in infant cells was due to cell death or impaired metabolic function. The results imply that the principles of growth regulation change postnatally. (Pediatr Res 29: 263–267, 1991)

ISSN:0031-3998    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

N-myconcogene expression was characterized in porcine kidneys to investigate the potential role of this gene in normal renal development and oncogenesis. N-mycRNA expression was detected in porcine kidneys from birth until 5 wk of age, which corresponds to the time when glomerular differentiation is completed. Immunohisto-chemical studies revealed that N-mycprotein was selectively expressed in the primordia of renal proximal tubule epithelial cells. These cells were cultured in vitro and continued to express N-mycfor a limited time. Comicroin-jection of a mutantrasoncogene and N-mycinto these cells led to focus formation in soft agar, loss of contact inhibition, and the establishment of an immortalized cell line. These findings support a multistep model of renal oncogenesis that involves overexpression of N-myc.(Pediatr Res29: 268–271, 1991)

ISSN:0031-3998    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

β-Blockers are used in pregnancy-associated hypertension and in postnatal cardiac arrhythmias, and the neonate may get them in breast milk. We therefore studied the effects of β-adrenergic medication on interrelations between heart rate (HR), respiration, and arterial blood pressure (aBP) in newborn lambs. The influence of sleep state on these cardiorespiratory interrelations was also examined. HR, aBP, and respiration (based on transthorack electrical impedance) were recorded and the sleep state was visually documented in five healthy chronically instrumented newborn lambs before the age of 30 d. Propranolol was given (1 mg/kg). Two-min stationary segments of the three signals were analyzed using a multivariate autoregressive model, which yields oscillations of the signals and intersignal relationships as source contributions. The variabilities of aBP and HR were greatest at the low frequencies (Pediatr Res 29: 272–277, 1991)

ISSN:0031-3998    

出版商:OVID    

年代:1991

数据来源: OVID