Expression of CD21 and CD23 during human fetal development

Neonates produce lower levels of IgE compared with adults. Diminished IL-4 production and impaired up-regulation of CD40L by neonatal T cells could explain this, however other regulators of IgE production, such as CD21 and CD23, could contribute to reduced circulating IgE levels during fetal development. Heparinized blood samples were collected from adults and from the umbilical cord at premature and term births. Whole blood flow cytometry was used to assess the percentage of T (CD3(+)) and B (CD19(+)) lymphocytes expressing CD21 and/or CD23 at 26-29 (n = 3), 30-33 (n = 7), 34-37 (n = 5), and >37 (n = 11) wk of gestation, as well as in adults (n = 15). Plasma-soluble CD21 was also measured. At term, the percentage of CD21(+) and CD23(+) B cells was comparable to the adult, however, the percentage of cells positive for each of these surface antigens was decreased significantly before term. The percentage of T cells expressing CD21 from all gestations was significantly higher than the adult and the percentage positive decreased with increasing gestational age. Conversely, soluble CD21 levels increased with increasing gestation to be comparable to the adult by term. Thus, it is unlikely that altered expression of CD21 and CD23 on B cells contributes to the low level of IgE in the neonatal circulation unless functional differences occur or a lack of processing to the soluble form is important in regulating IgE production. However the abundance of CD21-positive T cells could alter the T- and B-cell interaction necessary for IgE switching by B cells and, thereby, especially with impaired IL-4 production, limit IgE production.     

Gli2基因在胎鼠后肠发育后期的表达

目的探讨胎鼠后肠发育与sonichedgehog(Shh)基因转录因子Gli2基因表达水平的关系。方法48只妊娠Wistar大鼠随机分成2组,实验组(n=24)在孕11d按125mg/kg胃管注入1%乙烯硫脲(ethylenethiourea,ETU),对照组(n=24)给予等量蒸馏水。两组分别于孕12d、14d和16d各处死8只母鼠,每只母鼠取4只体重相似的胎鼠,取其直肠1cm提取RNA,采用半定量RT_PCR法检测Gli2基因表达。结果实验组胎鼠直肠Gli2基因表达水平明显低于对照组(P<0.05),实验组Gli2基因表达呈一低水平线,而对照组随妊娠时间呈一下降的曲线。结论Gli2基因表达水平在胎鼠后肠发育中具有重要的作用。     

Physiology of erythropoietin during mammalian development

Growth is a fundamental process of mammalian development. Several observations regarding regulation of erythropoiesis during growth are not easily explained by the hypoxia-erythropoietin (Epo) concept. This review focuses primarily on this aspect of the physiology of Epo. The question is raised of whether this regulation during growth is based on the hypoxia-Epo mechanism alone, or whether Epo acts in concert with general growth-promoting factors, particularly growth hormone (GH) and the insulin-like growth factors (IGF-I and -II). Supporting the latter hypothesis is the observation that the Epo and GH/IGF systems are activated by hypoxia and share similar receptors and pathways. Recent studies indicate that human fetal and infant growth is stimulated by GH, IGF-I and IGF-II. Epo, GH and IGFs are expressed early in fetal life. Although the rate of erythropoiesis in the fetus is high, serum Epo levels are low. The Epo response to hypoxia in the fetus and neonate is reduced compared with adults. Following delivery the Epo levels vary between species, probably related to the oxygen transport capacity of the hemoglobin (Hb) mass. IGF-I levels are low in the fetus and increase slowly following birth, except in preterm infants in whom the levels decline. In all mammals Hb declines following birth, giving rise to "early anemia". Except in the human, Epo levels increase proportionally with the fall in Hb, but there is a discrepancy between the curves for serum immunoreactive Epo (siEpo) and for erythropoiesis stimulating factors (ESF): the latter include other stimulatory factors in addition to Epo. Hypertransfusion of mice in the period of "early anemia" suppresses siEpo, but not ESF and erythropoiesis, as it does in adult mice. GH and IGF-I have direct effects on erythropoiesis in vitro and act particularly at the later stages of red cell differentiation. IGF-I acts synergistically with Epo, and its effects are most marked when Epo levels are low. Human recombinant (rhu) IGF-I stimulates erythropoiesis in neonatal rats, but not in newborn mice and lambs. In adult mice, in hypophysectomized rats and in mice with end-stage renal failure, however, a stimulatory effect of this growth factor was found on red cell production. RhuGH stimulates erythropoiesis in GH-deficient short children. CONCLUSION: Fetal and early postnatal erythropoiesis are dependent on factors in addition to Epo. The likely candidates are GH and IGF-I. The in vitro stimulating effects of these factors on erythropoiesis are convincing, but more data are needed on the in vivo effects.     

肾母细胞瘤和不同胎龄胚胎肾组织中端粒酶的原位表达

目的　以寻找人肾母细胞瘤发生的相关因素为出发点 ,以端粒酶的表达为线索 ,探索其在肾发育和肾母细胞瘤发生过程中的作用轨迹。方法　将实验对象分成三组 ,肿瘤组 :1999年 10月～ 2 0 0 2年 2月我院外科手术切除的肾母细胞瘤新鲜标本 18例。胎儿肾组 :2 4例 ,按胎龄分成 3小组 :12～ 2 0周 ,2 1～ 2 8周 ,2 9～ 36周 ,每小组各 8例。对照组 :非肿瘤肾 ,共 8例。将上述标本切片 ,用端粒酶 RNA原位杂交试剂盒进行检测。结果　肿瘤组的端粒酶 RNA阳性率为 72 .2 % (13/ 18) ,明显高于对照组 0 % (0 / 8) ,P =0 .0 0 2。 13例端粒酶 RNA表达阳性的肾母细胞瘤标本中 ,胚基成分和上皮成分的表达强度相近 ,分别为 8.10 77± 0 .1935 ,8.0 30 8± 0 .2 810 ,差别无统计学意义。它们的表达强度均远高于间质成分 (4 .6 0 0 0± 0 .2 5 82 ) ,差别具有显著性。在 18例人肾母细胞瘤的瘤旁肾中 ,有 8例 (4 4 % )可检测到肾源性剩余 (NR) ,其中有 7例有端粒酶 RNA的阳性表达 ,阳性率为38.9% (7/ 18)。将NR的形态和表达强度与其相对应的肾母细胞瘤中三种成分的形态和表达强度进行比较 ,发现从形态上 ,NR与肾母细胞瘤的胚基成分和上皮成分及其相似。从表达强度上 ,7例标本中的NR的阳性强度为 7.885 7± 0 .2 5 4 5 ,     

韧黏素在大鼠胚胎心脏发育过程中的表达

目的 检测韧黏素-C(TN-c)和韧黏素-X(TN-X)在大鼠胚胎心脏中的表达,探讨其在胚胎心脏发育过程中的作用.方法 雌性SD大鼠64只,雄性SD大鼠20只,雌雄同笼,以观察到雌鼠排出阴栓为妊娠0.5 d(ED 0.5),分别于ED 12.5、ED 15.5、ED 19.5处死孕鼠,取出心脏.半定量反转录酶聚合酶链反应(RT-PCR)检测上述各孕龄大鼠胚胎心脏中TN-C和TN-X mRNA表达;免疫组织化学染色法观察上述各孕龄大鼠心脏TN-C和TN-X蛋白表达.结果 TN-C mRNA在ED 12.5大鼠胚胎心脏中高表达(0.6837±00431),ED 15.5(0.4543±0.0388)和ED 19.5(0.2505 ±0.0384)大鼠胚胎心脏TN-C mRNA表达下降,与ED 12.5比较有显著性差异(Pa<0.05);ED 12.5、ED 15.5、ED 19.5大鼠心脏TN-X mRNA相对表达量分别为0.74711±0.0433、0.7584±0.070、0.767 1 ±0.088,各组间表达无显著性差异.免疫组织化学显示TN-c在ED 12.5大鼠胎心有表达,在ED 15.5少量表达,在ED 19.5大鼠心脏未见表达;TN-X在ED 12.5大鼠胎心的心室肌的细胞中有表达,在ED 15.5、ED 19.5胎鼠心脏中表达于整个心脏的心肌及房室间隔.结论 TN-c在胚胎心脏早期发育过程中可能占有重要作用,而TN-X可能是心脏存活所必须的.     

Hormonal regulation of renal function during development

The present review summarizes current and new knowledge concerning the major hormonal systems that directly or indirectly affect renal function during development. The role of the renin-angiotensin-aldosterone system in regulating renal function during fetal and postnatal life is reviewed. A summary of the role of this system during fetal and postnatal stresses is also provided. The physiological role of the renal kallikrein-kinin system in the control of renal blood flow, renin release and sodium excretion during development is examined. Possible influences of the prostaglandin system on regulation of renal function and renin secretion during fetal and postnatal maturation are explored. The effect of vasopressin on the ability of the fetal and postnatal kidney to concentrate urine and regulate body fluid homeostasis is reviewed in detail. The physiologic action of vasotocin on renal sodium and water homeostasis is described. New information regarding the role of the sympathetic system in the regulation of renal hemodynamics and in the control of renal function during development is presented. Finally, recent studies demonstrating the effect of atrial natriuretic factor and corticosteroids on the developing kidney are discussed.     

Post-burn reconstruction during growth and development

Modern plastic and reconstructive surgery continues to significantly improve the functional and aesthetic post-burn sequelae in children. It has become a major factor in restoring mobility, aesthetic appearance, self-esteem, and quality of life. The entire spectrum of plastic reconstructive procedures should be available to offer the patient an optimal solution to his problems. Therefore, early interdisciplinary co-operation between pediatric and plastic surgeons is mandatory to plan and perform post-burn reconstruction in children and adolescents.     

Birthweight and cognitive development during childhood

OBJECTIVES: Low birthweight has been reported to be associated with lower IQ at school age. Further, some evidence suggests that the association extends across the range of normal birthweights. This study assessed the relationship of birthweight to cognitive development in the Port Pirie birth cohort. METHODS: Of 723 singleton live births recruited into a prospective birth cohort study, 601, 548, 494 and 375 children were followed at ages 2, 4, 7 and 11-13 years, respectively. The children's developmental status was assessed using the Bayley Scales of Infant Development at age 2 years, the McCarthy Scales of Children's Abilities at age 4 years, and the revised Wechsler Intelligence Scale for Children at ages 7 and 11-13 years. The association between birthweight and cognitive function was assessed with multiple linear regression, adjusting for a wide range of possible confounders. RESULTS: The mean birthweight was 3386 g (SD: 517). There was a statistically significant association between birthweight and cognitive performance at age 2 years (adjusted deficit: 0.97 points per 100 g lighter; 95% CI: 0.4-1.5), but the magnitude of this association gradually decreased and became statistically non-significant at later childhood. CONCLUSIONS: The relationship between birthweight and cognitive development becomes progressively attenuated at increasing age. At older ages, socioenvironmental factors appear to play an increasingly important part in children's cognitive development.     

Xanthine oxidase during human fetal development

Through oxygen free-radical production, xanthine oxidase (XOD, E.C.1.2.3.2) has been implicated in the pathogenesis of postischemic and hyperoxic tissue injuries among newborn. We measured the activity and evaluated the kinetic characteristics of XOD in human fetal liver, intestine, brain, and myocardium. Both the fetal liver and intestine contain a high XOD activity through gestation. The activity increases in the liver and decreases in the intestine with advancing gestation. The apparent Km for hypoxanthine is 4.8-5.5 microM in the intestine throughout gestation and in the liver at term but higher than 30 microM in the liver during the first half of pregnancy. The activity is undetectable both in the fetal brain and myocardium throughout gestation. Thus, XOD activity is present at least in the liver and intestine to account for the oxidation of hypoxanthine and xanthine. However, direct evidence for adenine nucleotide catabolism, followed by oxidation of the accumulated hypoxanthine during tissue reoxygenation in the human liver or intestine is not available.     

Expression of hypoxia-inducible factors in normal human lung development.

Pulmonary vascular development is essential for proper lung development, and its disturbance can lead to neonatal morbidity and mortality, as exemplified in congenital diaphragmatic hernia. Hypoxia-inducible factors (HIFs) appear to be key molecules in physiologic angiogenesis and in certain forms of lung pathology, such as bronchopulmonary dysplasia. Little is known about the qualitative and quantitative expression of HIFs in normal human fetal lung development. Therefore, we investigated the expression of HIF-1alpha, HIF-2alpha, and HIF-3alpha, along with their upstream regulators and downstream targets, von Hippel-Lindau protein, vascular endothelial growth factor A (VEGF-A), and its receptor, VEGFR-2, in 20 normal human fetal lungs (13.5 weeks in gestation until term) and 5 adult lungs. Quantitative polymerase chain reaction demonstrated a positive correlation between HIF-2alpha and VEGF-A expression and gestational age. Although there appeared to be a decreasing trend in HIF-3alpha expression during pregnancy, it did not reach statistical significance. Immunohistochemistry for HIF-1alpha and HIF-2alpha revealed that HIF-1alpha is expressed in the epithelium, while HIF-2alpha is expressed in both interstitium and epithelium. Our data indicate that HIFs, most notably HIF-2alpha, appear to exert an important role in angiogenesis during human fetal lung development, especially in the last phases of pregnancy, preparing the fetus for extrauterine life. As such, our results form the baseline data for the evaluation and interpretation of abnormal pulmonary vascular development.     

Estimation of GnRH pulse amplitude during pubertal development

Fourteen children between 2.5 and 16 years of age were studied to provide a quantitative estimate of the changes in gonadotropin-releasing hormone (GnRH) pulse amplitude in hypophysial portal plasma during puberty. Responses to physiologic doses of synthetic GnRH were measured [induced luteinizing hormone (delta LH) and induced follicle-stimulating hormone (delta FHS)] and compared with spontaneous fluctuations in gonadotropins [spontaneous luteinizing hormone (delta sLH) and spontaneous follicle-stimulating hormone (delta FHS)]. One to four low-dose (0.0125 or 0.025 microgram/kg IV) pulses of GnRH were given every 2 hr between 0800 ad 1600 or 2200 and 0400 hr. Maximal peripheral plasma concentrations of GnRH one min after pulses averaged 107 +/- 25 pg/ml (S.E.) (0.0125 microgram/kg dose) and 218 +/- 33 pg/ml (0.025 microgram/kg dose). In early pubertal children the maximal delta LH was similar to or less than the maximal nocturnal delta sLH (maximum, delta LH 7.0 +/- 0.2 versus maximum delta sLH 7.0 +/- 1.3 mIU/ml in boys, 7.0 +/- 1.2 versus 16.0 +/- 3.0 mIU/ml in girls). Luteinizing hormone (LH) responses were low or undetectable in children whose bone ages were less than 10 years. When discernible, LH pulse frequency was similar during daytime and nighttime sampling periods in early pubertal boys. However, two hourly injections of GnRH given during the day did not simulate the initial nocturnal rise in LH. Overall mean delta FSH and delta sFSH were similar in three prepubertal female patients (3.0 +/- 0.2 versus 2.8 +/- 0.2 mIU/ml). delta FSH was greater than delta sFSH in two patients with gonadal dysgenesis (bone ages, 2.5 and 5 years) and in one prepubertal girl. The gonadotropin responses seen in early pubertal children suggests that the amplitude of nocturnal GnRH pulses is equal to or greater than that previously reported in normal men.     

Regulation of vasodilator synthesis during lung development.

The endothelium-derived vasodilator molecules prostaglandin I2 (PGI2) and nitric oxide (NO) are critically involved in the dramatic increase in pulmonary blood flow that occurs during cardiopulmonary transition at birth. Studies in animal and cell culture models have revealed that there is increased PGI2 and NO production in the pulmonary circulation of the late fetus in direct response to increased oxygenation, and that this response is unique to the pulmonary endothelium. Additional work has demonstrated that there is normally marked upregulation in the expression of the key synthetic enzymes cyclooxygenase type I and endothelial NO synthase in the lung during late gestation, thereby maximizing the capacity for vasodilator production at the time of birth. Furthermore, studies in animal models of neonatal pulmonary hypertension indicate that attenuated expression of these genes may frequently contribute to the pathogenesis of the disorder. A greater understanding of the mechanisms regulating PGI2 and NO synthesis in the developing lung will potentially lead to novel therapies for neonatal pulmonary hypertension aimed at optimizing endogenous vasodilator production.