Apolipoprotein A-1 in umbilical cord blood of newborn infants: relation to gestational age and high-density lipoprotein cholesterol

Apolipoprotein A-1 (Apo A-1) is the major protein constituent of high-density lipoprotein (HDL) and Apo A-1 plays an important role in lipid metabolism and may be protective against atherosclerosis in adults. However, little is known about HDL and Apo A-1 in the developing human fetus. Herein we investigated the relationship of Apo A-1 levels in umbilical cord blood at delivery to gestational age and HDL cholesterol. Fetal plasma levels of Apo A-1, which were not correlated with those in maternal plasma, were significantly lower among newborns delivered at 21-26 wk gestation (52 +/- 4.4 mg/dl, mean +/- SE) than in those delivered at 33-34 wk gestation (87 +/- 5.8 mg/dl). Thereafter, the mean umbilical cord plasma levels of Apo A-1 remained relatively constant (101 mg/dl at 39-40 wk of gestation). We found no significant correlations between Apo A-1 levels and fetal sex, race, or delivery method. At equivalent gestational ages and birth weights, however, Apo A-1 levels in white newborns tended to be lower than those in black infants. The Apo A-1/HDL cholesterol ratio in umbilical cord blood rose progressively from 2.5 (27-28 wk gestation) to 3.8 at term, due largely to increased Apo A-1 levels but little change in the mean HDL cholesterol levels, which ranged from 22-24 mg/dl at each gestational period. These results are suggestive that fetal plasma Apo A-1 is derived solely from fetal sources and that the rate of production and/or clearance of Apo A-1 is altered during the latter third of human intrauterine development.     

IGF-II and IGF binding protein (IGFBP-1, IGFBP-3) gene expression in fetal rhesus monkey tissues during the second and third trimesters

The IGF system is a key modulator of somatic fetal growth. Studies with human fetal tissues have shown a specific spatial and temporal pattern of expression of IGF and IGF binding protein (IGFBP) mRNAs, but have been limited to defined periods during gestation (i.e. 8-20 wk gestation) because of tissue availability. To fully assess the role of these peptides in the primate growth process, a longitudinal study was conducted that focused on the expression of IGF-II and IGFBP-1 and IGFBP-3 genes in the rhesus monkey (Macaca mulatta). Liver, kidney, brain, and lung were collected from rhesus monkey fetuses approximately every 2 wk from 65 (early second trimester) through 150 d gestation (term 165 +/- 10 d) (n = 50), then processed for in situ hybridization using radiolabeled human cDNAs. IGF-II mRNA was abundantly expressed in fetal kidney (maturing glomerulus, supporting mesenchyme, cells of the developing nephrons), liver (hepatocytes), cerebral cortex (choroid plexus, capillaries), and lung (blood vessels, connective tissues, lamina propria, cartilage framework). IGFBP-1 was expressed only in the hepatocytes and IGFBP-3 mRNA was modestly expressed within the kidney (developing nephrons, collecting system mesenchyme), and liver (hepatocytes). These studies have shown that (1) IGF-II, IGFBP-1, and IGFBP-3 are expressed in specific cell types of the fetal monkey indicating a paracrine/autocrine role during development; (2) changes in IGF-II and IGFBP mRNA expression occur with advancing gestation; and (3) fetal monkey tissues express IGF-II and IGFBPs in a similar manner when compared with the human fetus.     

Erythropoietin and hypoxia inducible factor-1 expression in the mid-trimester human fetus

AIM: Infants born prematurely lack a normal response to anemia and fail to increase erythropoietin (Epo) production despite an apparent need for improved tissue oxygenation. This anemia may involve a deficiency in the fetal and premature kidney to produce Epo. To evaluate fetal Epo production, Epo and hypoxia inducible factor-1 (HIF) mRNA expression was measured in the mid-trimester human fetus. METHODS: Fetal liver and kidney samples were obtained at 11-22 wk of gestation. RNA was isolated and reverse transcribed from snap-frozen specimens. Epo and HIF cDNA concentrations were determined using real-time polymerase chain reaction (PRISM). Epo cDNA concentrations were standardized to HIF concentrations present in each sample. RESULTS: HIF concentrations remained constant during gestation in kidney and liver samples. Epo cDNA concentrations in kidney did not change from 12 to 22 wk (8.4 +/- 3.4 fg Epo pg(-1) HIF cDNA, 4.8 +/- 1.4, 2.6 +/- 0.4, and 4.2 +/- 1.8 at 11-14, 15-16, 17-19, and 20-22 wk of gestation, respectively), while Epo cDNA concentrations in liver increased with gestation (74.5 +/- 31.9 fg pg(-1) HIF, 23.8 +/- 6.5, 96.4 +/- 19.2 and 276.1 +/- 28.5 at 12-14, 15-16, 17-19 and 20-22 wk of gestation, respectively, p < 0.05, 20-22 wk of gestation liver samples vs all other gestations). Concentrations were 5-20-fold higher in liver than in kidney in each gestational group (p < 0.01, liver vs kidney). CONCLUSION: HIF concentrations did not change with gestation in liver or kidney. The human fetal kidney produced approximately 5% of the total Epo mRNA measured during the second trimester. It remains to be determined how Epo production by these tissues is affected by premature birth.     

Ontogenic changes in serum immunoglobulins and C3 in vitamin-D deficient and malnourished rats

In both protein energy malnutrition and vitamin D deficiency, defects in some immunological functions have been noted, but the effects on complement and immunoglobulin concentrations have not been evaluated. We assessed the effects of malnutrition and vitamin D deficiency on immunoglobulins and C3 in rats in early postnatal life during weaning and early adulthood using the rocket immunoelectrophoresis technique. In well-nourished rats, the serum levels of IgG increased from 88.5 +/- 10.2 mg/dl in the newborn period to 883.4 +/- 104.8 mg/dl at weaning (day 19). The adult levels, 1,325.9 +/- 60.8 mg/dl, were attained by 35 days of age. Serum IgA was not detectable by our method until 20 days of age (1.1 +/- 0.2 mg/dl) and reached adult levels (13.4 +/- 3.2 mg/dl) by day 35. IgM was detectable in the serum of pups at 5 days of age (0.4 +/- 0.07 mg/dl), increased to 27.5 +/- 6.9 mg/dl at weaning and approached adult levels (93.7 +/- 9.9 mg/dl) at day 35. C3 levels at birth were only 36% of adult levels and did not change during the suckling period. They then increased to levels comparable to those of adults at the age of 35 days. Serum immunoglobulins and C3 in malnourished rats were not significantly different from age-matched control pups. In pups born to dams fed a vitamin-D-deficient diet from 3 weeks of age, only the serum IgG and C3 levels were significantly lower than those of normal pups at day 1 (IgG level: 65.2 +/- 6.1 vs. 88.5 +/- 10.2 mg/dl; C3 level: 20.3 +/- 6.9 vs. 36.2 +/- 3.1% of an adult level; p less than 0.005). Thus the increased susceptibility of malnourished young animals to infection does not appear to be related to a lowering of serum immunoglobulin and complement concentrations.     

Changes in 5alpha-pregnane steroids and neurosteroidogenic enzyme expression in the perinatal sheep

Pregnane steroids have sedative and neuroprotective effects on the brain as a result of interactions with the steroid-binding site of the GABAA receptor. To determine whether the fetal brain is able to synthesize pregnane steroids de novo from cholesterol, we measured the expression of cytochrome P450 side-chain cleavage (P450scc) and 5alpha-reductase type II (5alphaRII) enzymes in fetal sheep from 72 to 144 d gestation (term approximately 147 d) and in newborn lambs at 3 and 19-26 d of age. Both P450scc and 5alphaRII expression was detectable by 90 d gestation in the major regions of the brain and also in the adrenal glands. Expression increased with advancing gestation and was either maintained at fetal levels or increased further after birth. In contrast, the relatively high content (200-400 pmol/g) of allopregnanolone (5alpha-pregnan-3alpha-ol-20-one), a major sedative 5alpha-pregnane steroid, present throughout the brain from 90 d gestation to term, was reduced significantly (<50 pmol/g) immediately after birth. These results suggest that although the perinatal brain has the enzymes potentially to synthesize pregnane steroids de novo from cholesterol, either the placenta is a major source of these steroids to the brain or other factors associated with intrauterine life may be responsible for high levels of allopregnanolone production in the fetal brain until birth.     

Bone mineralization outcomes in human milk-fed preterm infants.

We evaluated bone mineralization by single photon absorptiometry at 2 y in a cohort of preterm infants studied since birth. Infants were fed human milk fortified with Ca [to achieve 80 mg/dL (19.96 mmol/L)] and P [40 mg/dL (12.91 mmol/L)] from wk 2 through 8 after birth. After hospital discharge, infants were divided into two groups (HM and F) determined by the timing of the introduction of cow milk-based formula. Mid-radius bone mineral content (BMC) was assessed in 10 infants who were breast-fed (HM) for a minimum of 2 mo after hospital discharge and 11 who were bottle-fed (F). The mean duration of human milk-feeding differed by design between HM and F groups (31 +/- 15 versus 11 +/- 3 wk, respectively). Although we had observed previously that group F had significantly greater BMC values at 16, 25, and 52 wk compared with values in group HM, we found similarities in BMC values (180 +/- 30 mg/cm) between groups at 2 y. The 2-y cohort comprised healthy infants and the groups had similar birth weights, lengths of gestation, and values for weight (10.8 +/- 1.1 kg), length (82 +/- 2 cm), and bone width (7.8 +/- 1.1 mm). Follow-up outcomes at 2 y in preterm infants fed fortified human milk in hospital suggest that if they continue to receive human milk after hospital discharge, radius BMC will "catch-up" to that of similar infants given formula in the posthospitalization period.     

Changes in plasma FcRIII demonstrate increasing receptor production during late pregnancy and after preterm birth.

We have previously described reduced expression of the Fc gamma receptor type III on the cell membrane (M-FcRIII) of neutrophils from very preterm neonates. To investigate the mechanism underlying this reduced receptor expression, we have measured neutrophil-derived soluble FcRIII (S-FcRIII) in the plasma of fetuses and neonates from 19 wk gestation. S-FcRIII in fetal plasma and in preterm neonates born before 32 wk gestation was consistently low [mean 13.6 +/- 1.2% (mean adult S-FcRIII = 100%, range 30-240%)]. In utero, S-FcRIII starts to rise from 33 wk and increases more than 4-fold to reach adult levels by term. S-FcRIII measured sequentially in preterm infants born as early as 24 wk of gestation showed a rapid postnatal increase to reach adult levels within 3 wk of birth. The changes in S-FcRIII paralleled changes in M-FcRIII expression on the cell surface. These observations point to a reduced rate of FcRIII production by fetal neutrophils as opposed to an increase in receptor release. The parallel increase in S-FcRIII and M-FcRIII suggests that there may be a programmed activation of FcRIII synthesis within individual cells late in the 3rd trimester of fetal development. In addition, FcRIII production may be switched on early by preterm birth.     

In vitro effect of multiplication stimulating activity (MSA) on human fetal and postnatal cartilage

Although insulin-like growth factors may have a physiological role in fetal growth, little is known of their biological action on human fetal tissues. In the present study, the action of multiplication stimulating activity (MSA) on human fetal cartilage in vitro, has been examined and compared with its effect on postnatal cartilage. Addition of MSA (10-100 ng/ml) resulted in a dose dependent increase in [3H]thymidine incorporation into fetal cartilage aged between 15 and 18 weeks of gestation. The mean response with 100 ng/ml was 143 +/- 18% (n = 10) of basal levels. The increase in [35S]sulphate incorporation was variable, the mean (131 +/- 36%, n = 5) being not significantly greater than in controls. The increase in [3H]thymidine incorporation on addition of MSA was not seen in fetal cartilage of earlier (13/14 wk) or later (19 wk) gestational age. MSA-III (a highly purified component of MSA) at 100 ng/ml increased [3H]thymidine and [35S]sulphate incorporation into cartilage from a fetus of 17 weeks to 165% and 150%, respectively, but had no effect on the incorporation of either isotope into cartilage from a fetus of 19 weeks gestation. In contrast to the mitogenic effects of MSA on fetal cartilage, the same preparation had no effect on either [3H]thymidine or [35S]sulphate incorporation into postnatal cartilage. These results may reflect developmental changes in cartilage response to insulin-like growth factors similar to those reported in human brain.     

Development of gastric histidine decarboxylase in the rat: sensitivity to fasting and secretagogues

Gastric mucosal histidine decarboxylase (HDase) was measured in fetal rats between days 16 and 21 of gestation, and in newborn rats up to weaning. HDase was not detected in fetal stomach. Its activity developed from day 1 after birth (29 +/- 2 pmol CO2/mg protein/h) and increased up to day 18 when it reached the fed adult level (894 +/- 174 pmol CO2/mg protein/h). Weaning increased HDase activity significantly (weaned versus unweaned rats: 1,664 +/- 150 and 1,036 +/- 170 pmol CO2/mg protein/h; p less than 0.005). Up to day 18, HDase activity was not altered by 16 h to 24 h of fasting. From that day on, HDase became sensitive to both pentagastrin and carbachol. These results indicate that complete functional maturation of histamine-producing cells is only reached at day 18, just before weaning. This developmental pattern may explain the differences observed between fetal and adult regulation of gastric acid secretion.     

Ontogeny of gastric function in the pig: acid secretion and the synthesis and secretion of gastrin.

Gastric acid secretion, gastrin-releasing peptide (GRP)-stimulated gastrin secretion and concentrations of somatostatin in gastric tissues were studied in sucking pigs (n = 48). In addition, gastrin concentrations in plasma and antral tissue were measured in fetal and sucking pigs (n = 66) from 22 days before birth (93 days gestation) to 36 days of age. From 3 days of age littermate pairs were treated twice a day with either saline (n = 20) or adrenocorticotropin [ACTH (1-24); n = 20]. Pentagastrin-stimulated acid secretion per unit stomach weight was 39 +/- 7 mumol H+/g/h at 0-1 day, increased to 194 +/- 15 mumol H+/g/h at 5-7 days and plateaued. Antral gastrin concentration was 0.14 nmol/g 10 days before birth and increased to 2.7 nmol/g at 5 weeks of age. Plasma gastrin was 25 +/- 2 pmol/l at 22 days before birth, increased to 102 +/- 14 pmol/l at birth and decreased during the postnatal period. Somatostatin concentrations were higher in antral than fundic tissues (p < 0.05) and remained constant during the postnatal period. Increased levels of glucocorticoids in plasma following ACTH treatment had no effect on the studied parameters except that it reduced basal (p < 0.07) and GRP-stimulated (p < 0.05) plasma gastrin concentrations at 6-7 days of age. Development of acid secretion and its gastric regulatory peptides in the pig is different from that in the rat in that it occurs at an earlier age and does not appear to be greatly influenced by elevated glucocorticoid levels from 3 days after birth.     

Absence of placental transfer of l-triiodothyronine (T3) in the rat

To detect placental transfer of L-triiodothyronine (T3) in pregnant rats, we injected 1 muCi [125I]T3 on the 16th, 18th, and 20th day of gestation. Three hours after the injection, which corresponds to the equilibrium time determined by a method of constant infusion, the pregnant rats and their fetuses were killed. The [125I]T3 was extracted from the serum or the homogenate by butanol extractions and alkaline washes. The transfer rate was calculated from the quantity of [125I]T3 in the serum of the fetuses after 3 hr and from the maternal metabolic clearance rate (8.19 +/- 0.45 ml/hr/100 g body weight; mean +/- SEM). At the 16th day of gestation, the placental transfer of T3 was 0.82 +/- 0.11% of the total maternal clearance rate/litter weight; it was 1.05 +/- 0.25% at the 18th day of gestation and 0.58 +/- 0.10% at the 20th day of gestation. There were no significant differences between these results. The maternal T3 concentration was 68.27 +/- 20.6 ng/100 ml and its production rate was 5.57 +/- 0.31 ng/hr/100 g; with these data we calculated a maternal-fetal T3 transfer of 46 +/- 6 pg/hr. Furthermore, there was no T3 transfer observed when the mother received 1.9 mug unlabeled T3, which led to a significant rise in maternal T3 concentration (68.27 +/- 20.6 ng to 102.23 +/- 7.41 ng/100 ml; P less than 0.01); there was no detectable T3 in the fetal serum. From these results we conclude that there is minimal or no placental transfer of T3 in the rat and that the hypothalamic-pituitary-thyroid axis of the fetus develops autonomously.     

Liver vitamin A reserves of very low birth weight neonates

This study assessed the liver vitamin A concentrations at birth in a group of very low birth weight neonates (n = 25) (less than 1500 g birth weight, less than 32 wk gestation), dying within 24 h of birth, prior to possible changes in vitamin A status induced by postnatal intervention. Serum concentrations of vitamin A and retinol-binding protein were also measured in 16 of these neonates. The mean (+/- SD) liver vitamin A concentration was 30.0 +/- 12.9 micrograms/g (range 2.0-49.0 micrograms/g). The mean (+/- SD) serum vitamin A concentration was 13.0 +/- 4.7 micrograms/dl (range 6.7-22.8 micrograms/dl). The mean (+/- SD) serum retinol-binding protein concentration was 2.2 +/- 0.8 mg/dl (range 1.5-4.8 mg/dl). Liver vitamin A, serum vitamin A, and serum retinol-binding protein concentrations did not correlate significantly with gestational age or birth weight. Linear regression analysis did not show a significant correlation between liver vitamin A, and serum vitamin A or retinol-binding protein concentrations. This study provides reference values for vitamin A concentrations at birth in very low birth weight neonates, which may be helpful in future studies designed to evaluate postnatal changes in the vitamin A status of these high-risk neonates.     

Serum levels of immunoreactive inhibin, FSH, and LH in human infants at preterm and term birth.

Serum levels of immunoreactive inhibin, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were determined in 112 fetal cord blood samples obtained at birth between 26 and 40 weeks of gestation. High levels of inhibin immunoreactivity were detected in all samples. Between the gestational age of 26 and 28 weeks, the levels (mean +/- SE) were higher (p less than 0.05) in male (21.6 +/- 1.0 U/ml; n = 12) than in female (12.8 +/- 0.2 U/ml; n = 12) fetuses. With ongoing gestation, the serum inhibin immunoreactivity decreased and was found to be similar in male (12.1 +/- 0.3 U/ml; n = 13) and female (9.1 +/- 0.7 U/ml; n = 8) fetuses at term. Serum FSH and LH levels were elevated at the beginning of the 3rd trimester of pregnancy and decreased with ongoing gestation to undetectable values at term birth. Between 26 and 32 weeks of gestation, the FSH levels were higher in females (p less than 0.02), whereas the LH levels were higher in males (p less than 0.01). These observations suggest that in the human fetus the pituitary-gonadal axis is active and presents sexual dimorphism; both characteristics are pronounced early during the 3rd trimester of gestation and decrease towards term.     

A developmental study on types and frequency distribution of short apneas (3 to 15 seconds) in term and preterm infants

We measured the frequency distribution and the ventilatory correlates of the various types of apneas 3 to 15 s long during sleep in eight term infants (birth weight 3.65 +/- 0.16 kg; gestational age 39.5 +/- 0.3 wk) and eight preterm infants (birth weight 2.07 +/- 0.18 kg; gestational age 34.3 +/- 0.4 wk). Each infant was studied on five to seven occasions from birth to 56 wk of postconceptual age using a modified flow-through system. Sixty-six paired epochs of quiet sleep (1163 min) and rapid eye movement sleep (829 min) were analyzed in term infants and 85 paired epochs of quiet sleep (1553 min) and rapid eye movement sleep (1328 min) in preterm infants. Of the 783 apneas recorded in term infants 82% were central, 1.5% obstructive, 0.5% mixed, and 16% were of the breath-holding type; the corresponding figures for the 4086 apneas recorded in preterm infants were 93, 0.5, 1.0, and 5.5%. This distribution was similar in the two sleep states but term infants had a higher percentage of breath-holding apneas than preterm infants (p less than 0.01). In preterm infants the rate of central apneas decreased with postnatal age (p less than 0.01); in term infants the rate did not change significantly. The duration of apneas showed a modal distribution for central apneas at about 8 s for both groups during the 1st month of life (p less than 0.05). The findings suggest: 1) apneas in the newborn and early infancy are primarily central and are more frequent in preterm than in term infants.(ABSTRACT TRUNCATED AT 250 WORDS)     

Thymidine factor in human cord sera and relationship to birth size, gestational age and insulin

Thymidine factor was studied in human cord sera from 44 neonates with gestational ages ranging between 36 and 43 weeks. Thymidine factor was determined by the uptake of 6-3H-thymidine using isolated chick embryo cartilage cells. The thymidine factors increased with gestational age and those of neonates at 40 weeks of gestation were 0.89 +/- 0.17 U/ml (mean +/- SD), but were significantly lower after 42 weeks of gestation. There was no correlation between thymidine factor in cord sera and birth weight or size. There was a positive correlation (p less than 0.02) between insulin level and thymidine factor in cord sera. Our data suggest that somatomedin measured as thymidine factor might not have a major role in fetal growth and insulin might be an important factor in the synthesis of somatomedin by the fetus.     

Alveolar epithelial cell differentiation and surfactant protein expression after mild preterm birth in sheep

As the transition to extrauterine life at birth alters the proportions of type I and II alveolar epithelial cells (AECs), our aim was to determine the effect of mild preterm birth on AECs and surfactant protein (SP) gene expression. Preterm lambs were born at approximately 133 d of gestational age (DGA); controls were born at term (approximately 147 DGA). Lungs were collected from preterm lambs at term-equivalent age (TEA; approximately 2 wk after preterm birth) and 6 wk post-TEA. Control lung tissue was collected from fetuses (at 132 DGA), as well as from lambs at approximately 6 h (normal term) and 2, 6, and 8 wk of postnatal age (PNA). In controls, the proportion of type I AECs decreased from 65.1 +/- 3.9% at term to 50.9 +/- 3.3%, while the proportion of type II AECs increased from 33.7 +/- 3.9% to 48.5 +/- 3.3% at 6 wk PNA. At 2 wk after preterm birth, the proportions of type I and II AECs were similar in preterm lambs compared to 132-d fetal levels and term controls but differed from control values at 2 wk PNA; differences between control and preterm lambs persisted at 8 wk PNA. At approximately 2 wk after preterm birth, SP-A and SP-B, but not SP-C, mRNA levels were significantly reduced in preterm lambs compared with term controls, but these differences did not persist at 2 and 6 wk PNA. We conclude that mild preterm birth alters the normal postnatal changes in type I and II cell proportions but does not severely affect SP gene expression.     

L-精氨酸对宫内发育迟缓胎鼠胰岛素样生长因子及其结合蛋白表达的影响

目的：宫内发育迟缓(IUGR)儿常有脑发育的异常,L精氨酸具有舒张血管、增加胎盘血流的作用,可用于改善胎盘缺氧状态,促进胎儿生长发育。用被动吸烟法制作孕鼠IUGR模型,孕8～20d给予不同剂量L精氨酸,了解其对宫内发育迟缓胎鼠脑内胰岛素样生长因子及其结合蛋白表达的影响,并探讨L精氨酸的作用机制。方法：孕鼠随机分为4组:对照组、模型组、L精氨酸小剂量和大剂量防治组,每组9只。孕21d剖宫取胎,应用酶联免疫吸附法检测各组胎鼠脑组织胰岛素样生长因子Ⅰ(IGFⅠ)、胰岛素样生长因子Ⅱ(IGFⅡ)、胰岛素样生长因子结合蛋白(IGFBP3)含量,应用荧光定量RTPCR法检测各组胎鼠脑组织IGFⅠmRNA表达。结果：与对照组相比较,模型组胎鼠脑组织中IGFⅠ(0.789±0.062ng/mgvs0.947±0.042ng/mg)、IGFⅡ(0.270±0.020ng/mgvs0.374±0.015ng/mg)含量均比对照组明显降低,IGFBP3(0.253±0.011ng/mgvs0.089±0.015ng/mg)含量比对照组明显升高,IGFⅠmRNA表达量(13.12±1.39)×104cps/μgRNAvs(21.28±3.54)×104cps/μgRNA比对照组明显降低,差异均有显著性(P<0.01)。与模型组相比较,小剂量和大剂量L精氨酸防治组IGFⅠ含量明显增高,分别为0.937±0.067ng/mg和0.858±0.077ng/mg,IGFⅡ含量明显增高,分别为0.318±0.018ng/mg和0.354±0.021ng/mg,IGFBP3含量明显降低,分别为0.132±0.006ng/mg和0.146±0.009ng/mg差异有显著性(P<0.01或<0.05)。同时小剂量和大剂量L精氨酸防治组IGFⅠmRNA表达量也明显增高,分别为(19.24±2.48)×104cps/μgRNA和(17.35±2.30)×104cps/μgRNAvs(13.12±1.39)×104cps/μgRNA,差异均有显著性(P<0.01)。结论：L精氨酸可增加被动吸烟致宫内发育迟缓胎鼠脑内IGFⅠ、IGFⅡ含量和IGFⅠmRNA的表达,降低IGFBP3含量。L精氨酸防治IUGR的机制与其对胰岛素样生长因子及其结合蛋白表达的影响有关。     

Isovaleryl-CoA dehydrogenase activity in isovaleric acidemia fibroblasts using an improved tritium release assay

Isovaleric acidemia is a disorder of leucine metabolism caused by a deficiency of isovaleryl-CoA dehydrogenase. At least two clinical subgroups of patients exist: a severe form, in which symptoms occur within the 1st wk of life, and a milder variant in which manifestations develop later in life. We developed a modified version of the tritium release assay to accurately measure residual isovaleryl-CoA dehydrogenase activity in fibroblasts from patients with both forms of isovaleric acidemia. In the modified assay, specific isovaleryl-CoA dehydrogenase-catalyzed tritium release from [2,3-3H]isovaleryl-CoA was determined by including an inhibitor of isovaleryl-CoA dehydrogenase, (methylenecyclopropyl)acetyl-CoA, in one of the tubes in paired assays, to determine the nonspecifically released 3H2O. Residual activities of the nine isovaleric acidemia lines tested ranged from 0 to 0.67 pmol 3H2O/min/mg protein (controls 19.4 +/- 8.0). The three lines from mildly affected individuals all had no detectable activity, whereas the severe cases had a mean of 0.41 pmol 3H2O/min/mg protein. Normal human fibroblast isovaleryl-CoA dehydrogenase had a Km for isovaleryl-CoA of 22 microM, with a Vmax of 51 pmol 3H2O/min/mg protein. The Ki of isovaleryl-CoA dehydrogenase by (methylenecyclopropyl)acetyl-CoA was approximately 2 microM.     

Small preterm infants (less than or equal to 1500 g) have only a sustained decrease in ventilation in response to hypoxia.

The classic "biphasic" ventilatory response to 15% O2 was previously observed in preterm infants who were large compared with those in the intensive care nursery today. We hypothesized that in the smaller infant (less than or equal to 1500 g) the response might be closer to that of the fetus, with no initial increase in ventilation. Thus, we studied 14 healthy preterm infants less than or equal to 1500 g [birth weight 1200 +/- 63 g (mean +/- SEM); gestational age 29 +/- 0.4 wk; postnatal age 17 +/- 3 d] during rapid eye movement and quiet sleep. Ventilation was measured using a nosepiece and a flow-through system. Sleep states were defined using EEG, electro-oculogram, and body movements. After a control period in 21% O2 (3 min), infants breathed 15% O2 for 5 min. In rapid eye movement sleep, minute ventilation decreased from 0.186 +/- 0.020 (control) to 0.178 +/- 0.021 (30 s), to 0.171 +/- 0.017 (1 min; p = 0.03), to 0.145 +/- 0.016 (3 min; p = 0.002), and to 0.129 +/- 0.011 l.min-1.kg-1 (5 min; p = 0.004). In quiet sleep, it decreased from 0.173 +/- 0.019 (control) to 0.164 +/- 0.019 (30 s), to 0.166 +/- 0.019 (1 min), to 0.148 +/- 0.013 (3 min; p = 0.03), and to 0.146 +/- 0.012 l.min-1.kg-1 (5 min; p = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum growth-promoting activity in normal and hypotrophic fetuses at midpregnancy

Blood from 24 human fetuses aged 19-24 wk was collected by ultrasound-guided puncture of the umbilical cord in utero, performed for prenatal diagnosis of mother to fetus transmissible infections. Fetal serum growth-promoting activity (thymidine activity) was measured by its effect on 3H-thymidine incorporation into human lectin-activated lymphocytes. Ten blood samples were obtained at 19-22 wk of pregnancy and 14 at 23-24 wk. The pregnancies were maintained and the fetuses delivered, free of infection, at 38-40 wk, nine of them being small for date and 15 having a normal weight for gestation age. The bioassayable thymidine activity was significantly lower in the hypotrophic (0.84 +/- 0.04 U/ml) than in the normal fetuses (1.28 +/- 0.09 U/ml) whatever the time of sampling. Thymidine activity was significantly negatively correlated with gestational age in the normal for date fetuses, not in the small for date. It is suggested that early measurement of thymidine activity in fetal blood might be of value in the assessment of fetal growth despite the fact that the tissue growth factors may be more important in fetus than are the serum factors.