bluuebunny/crossref_metadata_2025 huggingface dataset:
Correcting for Cryptic Relatedness in Population-Based Association Studies of Continuous Traits
Authors: Zhang Feng , Deng Hong-Wen
Published: October 2009

Cryptic relatedness was suggested to be an important source of confounding in population-based association studies (PBAS). The magnitude and manner of cryptic relatedness affecting the performance of PBAS of continuous traits remain to be investigated. We simulated a set of related samples through biased sampling and inbreeding, and evaluated the power and type I error rates of simple association tests (SAT) without correcting for cryptic relatedness. We also used extended likelihood ratio tests (ELRT) to conduct PBAS accounting for cryptic relatedness, and compared it with genomic control (GC). Cryptic relatedness decreased the power as well as increased the type I error rates of SAT in both biased sampling and inbreeding models. The impact of cryptic relatedness on the performance of SAT appeared to be limited in the biased sampling model. However, cryptic relatedness in inbred populations may result in excessive false positive results of SAT. Compared with SAT and GC, ELRT obtained improved power and type I error rates under various scenarios. Ignoring cryptic relatedness may increase spurious association results in PBAS. Our ELRT provides a novel approach to control cryptic relatedness in PBAS of human continuous traits.
The Diversity Profile of TP53 Is Influenced by Positive Selection on the Immediately Upstream Locus WDR79
Authors: Alonso Santos , Izagirre Neskuts , López Saioa , Smith-Zubiaga Isabel , Hervella Montse , Boyano María Dolores , Arroyo-Berdugo Yoana , Gardeazabal Jesús , Díaz-Ramón José Luís , Sánchez Díez Ana , Careaga Jesus María , de la Rúa Concepción
Published: October 2009

Background/Aim:TP53 is an efficient central node in a signal transduction network that responds to minimize cancer. However, over 50% of tumors show some mutation in TP53. Thus, one might argue that this single central node network lacks robustness. Therefore, we wanted to investigate if natural selection has played a role in shaping the genomic region containing TP53. Methods: We have analyzed the HapMap data for evidence of selection using FST pairwise comparisons and the extended haplotype homozygosity test on a 200-kb region encompassing TP53. We have also resequenced 4 kb upstream TP53 in Europeans (including melanoma patients), Asians, Australian Aborigines and Africans. Results: Genetic hitchhiking by a linked, positively selected allele at the nearby gene WDR79 may be partly responsible for the sequence diversity profile of TP53. It can help explain why the TP53 Arg72 allele is the major allele in Europeans even when the alternative allele, 72Pro, has been reported to offer an increased longevity after disease. Conclusions: Despite the important role of TP53, a complex interplay with other evolutionary forces, which are extrinsic to TP53 function, may have driven the genetic diversity pattern of this locus, and, as a consequence, its structure and function.
Pair-Wise Multifactor Dimensionality Reduction Method to Detect Gene-Gene Interactions in A Case-Control Study
Authors: He H. , Oetting W.S. , Brott M.J. , Basu S.
Published: October 2009

Objective: The identification of gene-gene interactions has been limited by small sample size and large number of potential interactions between genes. To address this issue, Ritchie et al. [2001] have proposed multifactor dimensionality reduction (MDR) method to detect polymorphisms associated with the disease risk. The MDR reduces the dimension of the genetic factors by classifying them into high-risk and low-risk groups. The strong point in favor of MDR is that it can detect interactions in absence of significant main effects. However, it often suffers from the sparseness of the cells in high-dimensional contingency tables, since it cannot classify an empty cell as high risk or low risk. Method: We propose a pair-wise multifactor dimensionality reduction (PWMDR) approach to address the issue of MDR in classifying sparse or empty cells. Instead of looking at the higher dimensional contingency table, we score each pair-wise interaction of the genetic factors involved and combine the scores of all such pairwise interactions. Results: Simulation studies showed that the PWMDR generally had greater power than MDR to detect third order interactions for polymorphisms with low allele frequencies. The PWMDR also outperformed the MDR in detecting gene-gene interaction on a kidney transplant dataset. Conclusion: The PWMDR outperformed the MDR to detect polymorphisms with low frequencies.
The Germinative Zone Produces the Most Cortical Astrocytes after Neuronal Migration in the Developing Mammalian Brain
Authors: Gressens Pierre , Richelme Christian , Kadhim Hazim J. , Gadisseux Jean-François , Evrard Philippe
Published: October 2009

The origin of astrocytes of the mouse neocortex during the fetal and early postnatal periods as determined by immunocytological, autoradiographic, electron microscopic and antimitotic methods is described. Most astrocytes destined for the white matter and the infragranular cortical layers are derived from the transformation of radial glial cells between P0 and P10 with an inside-out pattern. This cell metamorphosis is not directly preceded by mitosis and involves the activation of the radial glial lysosomal apparatus. In opposition to recent hypotheses, our findings suggest that most astroyctes destined for the supragranular cortical layers are produced in the germinative zone after the migration of the infragranular neurons and themselves migrate afterwards to the upper cortex between E16 and the first postnatal days. These astrocytes do not display an intermediate stage of the radial glial cell and do not participate in the pattern of appearance of the deeper astrocytes. This second step of astrocytogenesis is a condition for normal cytoarchitectonic development and the maintenance of the supragranular layers, since the deprivation of the astrocytic equipment of the supragranular layers by an antimitotic drug drastically reduces the number of supragranular neurons.
Effect of Graded Hypoxia on Brain Cell Membrane Injury in Newborn Piglets
Authors: DiGiacomo Jane E. , Pane Carmela R. , Gwiazdowski Steven , Mishra Om P. , Delivoria-Papadopoulos Maria
Published: October 2009

Alterations in brain cell membrane structure and function during cerebral hypoxia were investigated by measuring Na+, K+-ATPase activity and levels of lipid peroxidation products in brain cell membranes obtained from newborn piglets following exposure to 60 min of hypoxic hypoxia in vivo. Cerebral hypoxia was documented as a decrease in the ratio of phosphocreatine to inorganic phosphate (PCr/Pi) using 31P-NMR spectroscopy. During hypoxia (FiO2 0.07-0.11), PCr/Pi decreased 28–47% compared to the corresponding baseline value without a decrease in cerebral ATP levels. No change in brain cell membrane Na+, K+-ATPase activity was observed for changes in PCr/Pi of < 30%. When PCr/Pi was at least 30% lower than baseline, Na+, K+-ATPase activity decreased linearly as a function of the decrease in PCr/Pi (r = 0.95). Levels of lipid peroxidation products (conjugated dienes and fluorescent compounds) increased significantly as PCr/Pi decreased. These data suggest that below a critical threshold value of oxidative metabolism there are progressive changes in brain cell membrane structure and function during cerebral hypoxia, and demonstrate that membrane alterations occur prior to changes in cellular ATP levels.
Brain Cell Membrane Dysfunction following Acute Asphyxia in Newborn Piglets
Authors: Goplerud Jan M. , Mishra Om Prakash , Delivoria-Papadopoulos Maria
Published: October 2009

Brain cell membrane function during and following single and repeated episodes of asphyxia was investigated. Asphyxia in 24 anesthetized, paralyzed, mechanically-ventilated newborn piglets was produced by stopping ventilation for 2–3 min followed by recovery with reventilation. Measurements of cerebral Na+, K+-ATPase activity and of lipid peroxidation products, conjugated dienes and fluorescent compounds, were made during control (n = 12), asphyxia (n = 5), recovery after a single asphyxia event (n = 4), and recovery following 7 repeated asphyxia episodes (n = 3). Cerebral Na+, K+-ATPase activity remained unchanged from control during asphyxia (14.57 ± 2.43 compared to 15.33 ± 4.27 μmol Pi/mg protein/h, mean ± SD), but was significantly reduced both during recovery after single (3.87 ± 1.66) and after repeated (2.59 ± 1.58) asphyxias, representing a 73 and 82% reduction in enzyme activity, respectively. Conjugated dienes and fluorescent compounds were similarly unchanged during asphyxia compared to control, but increased during recovery from single and from repeated episodes. Decreased cerebral Na+, K+-ATPase activity, simultaneous with an increase in lipid peroxidation products, reflects significant cellular membrane damage consistent with oxygen free radical formation during the recovery from acute asphyxia in the newborn piglet.
Plasma Manganese Levels in the Very Low Birth Weight Infant Are High in Early Life
Authors: Wilson D.C. , Tubman T.R.J. , Halliday H.L. , McMaster D.
Published: October 2009

Plasma manganese levels were determined at birth and then serially to 3 months of age in 40 very low birth weight (VLBW) infants (mean birth weight 1,027 g). Mean plasma manganese concentration was 3.6 μg/l at birth and 3.0 μg/l at 3 months of age. These levels were approximately 3-fold greater than those of a group of 9 adults analysed using the same methods (mean 1.1 μg/l). Manganese was also measured in parenteral nutrition fluids, breast milk and 3 preterm formulas. There was no relationship between manganese intake and plasma manganese concentration.
Epidermal Growth Factor in the Neonatal Mouse Salivary Gland and Kidney
Authors: Gattone II Vincent H. , Sherman Denise A. , Hinton Duane A. , Fu-wen Niu , Topham Todd , Klein Robert M.
Published: October 2009

In the adult mouse, epidermal growth factor (EGF) is synthesized in granular convoluted tubule (intralobular) duct cells of the submandibular gland and in distal tubule cells of the kidney. The presence of EGF in developing tissues and maternal milk and the localization of EGF receptors in developing tissues suggest a role for EGF in developmental processes. The primary aims of the present study were to: (1) localize EGF and EGF-binding sites in the kidney and submandibular gland during neonatal development and (2) to determine the effect of exogenously administered EGF on cell proliferation in these two developing organs. In the present study, EGF was localized by immunocytochemistry in granular convoluted tubule cells of the submandibular gland initially on day 21 after birth and in distal tubule cells of the kidney on postnatal day 6. EGF binding in the kidney decreased after birth with some localization to the glomerulus. In submandibular glands of newborn and 10-day-old mice, EGF-binding sites were associated with both acinar and duct cells with peak binding at 10 days postnatally. Submandibular glands from 20-day-old mice demonstrated primarily ductal EGF-binding sites. Exogenously administered EGF induced a mitogenic response in acinar and interlobular duct cells of submandibular glands during the first week after birth. EGF treatment during this period had an inhibitory effect on 3H-thymidine incorporation into cellular compartments in the developing kidney. The identification of EGF-binding sites in the kidney and submandibular gland before the presence of EGF suggests that an EGF-like molecule such as transforming growth factor α (TGF-α) may be present as a potential ligand in these organs. In order to assess this possibility, developing kidneys and submandibular glands were stained with anti-TGF-α. These immunocytochemical studies localized TGF-α to the proximal tubule of the kidney and immature acinar cells of the newborn mouse. Our data strongly support an autocrine, juxtacrine or paracrine role for EGF and/or TGF-α in the regulation of cell proliferation and cytodifferentiation in the kidney and submandibular gland.
Oxygen Saturation during Sleep in Patients with Bronchopulmonary Dysplasia
Authors: Zinman Raezelle , Blanchard Pierre W. , Vachon Francine
Published: October 2009

We hypothesized that significant sleep desaturation might occur in infants with bronchopulmonary dysplasia whose awake saturations were between 90 and 92%. Supplemental oxygen was continued until the awake saturation on room air was 90% or greater. Sleep saturations were monitored by oximetry sampling for a 3-min period every hour overnight. Significant desaturation was considered to be present if the saturation fell repeatedly below 88%. There were 39 studies performed in room air, and 14 studies in supplemental oxygen. We demonstrated that patients with acceptable awake saturation may desaturate while sleeping. However, only 1 of 25 patients whose saturation in room air was 92% or more repeatedly desaturated during sleep.
Significance of Phototherapy-Induced Riboflavin Deficiency in the Full-Term Neonate
Authors: Amin H.J. , Shukla A.K. , Snyder F. , Fung E. , Anderson N.M. , Parsons E.G.
Published: October 2009

As a result of impaired fatty acid oxidation, a characteristic urinary dicarboxylic aciduria occurs in the riboflavin deficient animal. We compared the occurrence of riboflavin deficiency induced by phototherapy with changes in urinary organic acid profiles in 8 full-term, breast-fed neonates who received phototherapy for hyperbilirubinemia, and in 10 full-term, breastfed controls. Riboflavin status was assessed by measuring flavin adenine dinucleotide saturation of erythrocyte glutathione reductase. All 8 neonates exposed to phototherapy developed riboflavin deficiency (p < 0.001). Riboflavin deficiency was progressive with the duration of phototherapy. None of the controls was riboflavin deficient. Urine organic acid profiles indicative of mitochondrial acyl-CoA dehydrogenase activity (fatty acid β-oxidation, quantitated by gas chromatography mass spectrometry) showed no changes between the study and control groups in mono-, di-, or tricarboxylic acids or other organic acids. The riboflavin deficiency induced by phototherapy in full-term neonates was not of sufficient severity to limit riboflavin-dependent fatty acid oxidation.
Effect of Bombesin on the Development of the Neonatal Rabbit Gastrointestinal Tract
Authors: Karkashan Eman M. , MacNaughton Wallace K. , Gall Grant
Published: October 2009

The effect of bombesin on the postnatal development of the gastrointestinal tract was examined in New Zealand white rabbits. Bombesin (1.25, 12.5, 30 μg/kg body weight) or vehicle was administered intraperitoneally to suckling rabbits for 13 days starting on day 4 of life. The animals were killed at day 17. There was no significant effect of bombesin at doses of 1.25 or 12.5 μg/kg in any region of the gut studied. Bombesin administered at 30 μg/kg induced a widespread trophic effect in the gastrointestinal tract characterized by significant increases in the wet weight of the stomach, liver and whole small intestine, as well as in 10-cm segments of the proximal, middle, and distal small intestine. There was also a significant increase in the mucosal weight of 10-cm segments of the proximal, middle and distal small intestine, and the colon in the bombesin-treated group. Bombesin significantly increased the protein and DNA contents of the liver, the fundus of stomach, all segments of the small intestine and the distal colon. Maximal stimulation was seen in DNA content, suggesting that bombesin has a primarily hyperplastic effect. Bombesin increased the activities of small intestinal sucrase and maltase but not lactase. Bombesin did not alter hepatic glucokinase activity. These findings suggest that bombesin can promote the growth of the neonatal rabbit gastrointestinal tract and liver.
Development of Aldehyde Dehydrogenase and Alcohol Dehydrogenase in Mouse Eye: Evidence for Light-Induced Changes
Authors: Dowries John , Holmes Roger
Published: October 2009

We have studied the development of ocular aldehyde dehydrogenase (ALDH) and alcohol dehydrogenase (ADH) activities in C57BL/6J inbred male mice. Eyes were removed from freshly killed mice, enucleated, extracted, and analyzed for enzyme activities for animals of various ages during neonatal development, up to the adult stage. Activity levels were compared between mice maintained from birth in either complete darkness or on a 12-hour light/dark cycle. Ocular ALDH activity increased dramatically ( > 30-fold) during the first 3 weeks of life. Moreover, light-adapted animals showed significantly higher ALDH activities from day 8. Ocular ADH activity also increased during development (> 5-fold) although the profile showed a steady increase to reach adult levels. Light-adapted mice showed no significant differences in ADH activity up to the weaning stage, as compared with mice maintained in darkness. These observations support proposals from earlier studies for major functional roles for both corneal ALDH and ADH in protecting the eye against ultraviolet light-induced damage.
Placental Alterations, Intrauterine Growth Retardation and Teratogenicity Associated with Enalapril Use in Pregnant Rats
Authors: Valdés Gloria , Marinovic Daniela , Falcón Cristián , Chuaqui Rodrigo , Duarte Ignacio
Published: October 2009

Enalapril (15 mg/kg/day p.o.) was given to 11 pregnant rats from day 1 to 9 (E1–9) and to 11 rats from day 10 to 20 (E10–20) of pregnancy; 12 rats were the control group. Fifteen animals were sacrificed on day 20 of pregnancy and 19 were allowed to progress into partum. Placentas were smaller in E10–20 rats (––15%, p < 0.05) and had a simple hypocellular cordonal structure; in E1–9 animals the predominant pattern was a combination of complex and simple structure. At day 20 the fetuses in the treated groups were smaller than the controls (––5% in E1–9 and ––16% in E10–20, p < 0.05); differences disappeared on the 13th day postpartum. Two fetuses from treated mothers presented incomplete skull ossification. We believe this report adds arguments to preclude converting enzyme inhibitors in pregnancy.
Detailed Expression Pattern of Foxp1 and Its Possible Roles in Neurons of the Spinal Cord during Embryogenesis
Authors: Morikawa Yoshihiro , Komori Tadasuke , Hisaoka Tomoko , Senba Emiko
Published: October 2009

A member of winged-helix/forkhead transcription factors, Foxp1, is expressed in the developing spinal cord during mouse embryogenesis. To shed light on the potential role of Foxp1 in neurons of the developing spinal cord, we investigated the detailed expression pattern of Foxp1 between embryonic day (E) 9.5 and E17.5. At E10.25, some postmitotic neurons with strong expression of Foxp1 (Foxp1high) were first detected in the ventral half of the brachial spinal cord. By E11.5, Foxp1high neurons increased in the ventral spinal cord at the limb levels. All of Foxp1high neurons at the limb levels were Islet2+/Lhx3– motor neurons (MNs) of the lateral motor column and some neurons that expressed Foxp1 weakly (Foxp1low) at the thoracic level were MNs of the preganglionic motor column. Between E12.5 and E17.5, Foxp1low neurons were also observed in the intermediate zone throughout the ventral spinal cord, all of which were Pax2+, En1+, Evx1–, Chx10–, Gata3–, and Lhx3– V1 interneurons. Interestingly, no colocalization of Foxp1 with Lhx3 was observed in the developing spinal cord. In addition, overexpression of Foxp1 markedly attenuated the endogenous expression of Lhx3 in a neuroendocrine cell line. Chromatin immunoprecipitation assays in a neuronal cell line and E13.5 spinal cords revealed an interaction between Foxp1 and the consensus motif in the Lhx3 promoter. These results suggest that Foxp1 may play some important roles in the determination of neuronal fates of the ventral spinal cord, possibly through the suppression of Lhx3 expression.
Neonatal B Lymphocyte Subpopulations and Method of Delivery
Authors: Gasparoni Antonella , Maccario Rita , Chirico Gaetano , Belloni Cesare , Mingrat Gabriella , De Amici Donatella , Bonora Mario Regazzi , Rondini Giorgio
Published: October 2009

We studied four groups of healthy term newborn infants: (1) 11 infants born by vaginal delivery; (2) 11 infants born by elective cesarean section; (3) 10 infants born by emergency cesarean section with labor, and (4) 10 infants born by complicated vaginal delivery. Total and differential leukocyte counts, cortisol blood level, and B lymphocyte subpopulations (SmIg, sIgD, sIgM, CD 19, CD20, CD21, CD23) were evaluated in cord blood samples from the four infant groups. Furthermore, the Pentothal blood level was measured in infants born by elective cesarean section and in their mothers at delivery. Higher total and differential leukocyte counts and cortisol blood levels were observed in group 1 and 4 infants as compared with group 2 and 3 infants. A significant correlation was observed between cortisol blood level and leukocyte counts. The percentages of positivity to cell surface markers of B lymphocyte subpopulations were significantly higher in infants born by elective cesarean section. A negative significant correlation of thiopentone with sIgM and CD21 was observed. These data indicate a significant influence of method of delivery and of thiopentone on B lymphocyte subpopulations.
Long-Term Variability of Heart Rate Increases with Successful Closure of Patent Ductus arteriosus in Preterm Infants
Authors: Prietsch Viola , Maier Rolf , Schmitz Lothar , Obladen Michael
Published: October 2009

Long-term variability (LTV) of heart rate was calculated continuously by a microprocessor in 25 preterm infants undergoing indomethacin treatment for closure of patent ductus arteriosus (PDA), in 24 preterm infants without signs of PDA, and in 10 neonates treated with prostaglandin E1 for cyanotic heart malformation. In infants with patent ductus arteriosus, LTV was lower than in controls. Following indomethacin, LTV increased most markedly (from 1.5 to 3.2; p < 0.01) in infants with improved ventilation. The increase was less marked (from 1.8 to 2.5; p < 0.05) in infants whose degree of respiratory failure did not change. LTV remained largely unchanged in infants who deteriorated. In 9 out of the 10 neonates treated with prostaglandin E1, LTV increased. We conclude that LTV corresponds to brain stem oxygenation and may be a useful tool to monitor treatment of PDA.
Serum Levels of Immunoreactive Inhibin, FSH, and LH in Human Infants at Preterm and Term Birth
Authors: Massa G. , de Zegher F. , Vanderschueren-Lodeweyckx M.
Published: October 2009

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 < 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 < 0.02), whereas the LH levels were higher in males (p < 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.
Two-Color Flow Cytometric Analysis of Natural Killer and Cytotoxic T-Lymphocyte Subsets in Peripheral Blood of Normal Human Neonates
Authors: Slukvin Igor I. , Chernishov Victor P.
Published: October 2009

It has been demonstrated that normal human newborns had significantly lower percentages of CD8+, CD11b+, CD 16+ and CD 56+, compared to adults, while no differences had been noted for the absolute numbers of these cells. Both the proportions and absolute numbers of CD 5 7+ lymphocytes and cytotoxic T cells that mediate non-MHC-restricted cytotoxicity (CD3+CD56+) were markedly reduced in neonatal blood. Mean proportions but not absolute numbers of precursors and effectors of allocytotoxic T cells (CD8+CD11b––) significantly decreased in human neonates. Dual-labeling experiments demonstrated that newborns’ natural killer cells had a phenotype different from that of adults. In newborns, there were much higher levels of CD1 1b+ cells, much lower levels of CD57+ cells and similar levels of CD8+ lymphocytes among CD 16+ lymphocytes. It seems that a phenotype immaturity of natural killer cells may contribute to the diminished cytotoxic potential of neonatal lymphocytes.
Effects of Birth Asphyxia on Urinary Organic Acid Excretion
Authors: Walker V. , Mills G.A.
Published: October 2009

Using capillary gas chromatography-mass spectrometry, the effects of birth asphyxia on the urinary organic acid profile of term babies was investigated. Random urine samples were collected on days 1 and 8 from 19 babies with fetal distress, 19 with moderate birth asphyxia and 12 with severe asphyxia causing encephalopathy. Controls were 27 well neonates. Statistically significant abnormalities were found only for the severely asphyxiated group: increased concentrations of lactic, pyruvic, 3-hydroxybutyric, 4-hydroxyphenyllactic and 4-hydroxy-3-methoxymandelic acids, and excretion of four abnormal metabolites, 2-hydroxybutyric, 2-oxoisocaproic, 2-hydroxyisovaleric and 2-oxo-3-methylvaleric acids. Six other babies had increased lactic acid excretion, associated in four with transient ‘jitterness’ or hypotonia. Organic acid studies may help to grade the severity of perinatal asphyxia in the outcome or intervention studies.
Comparative Study of the Binding of Prolactin and Growth Hormone by Rabbit and Human Lung Cell Membrane Fractions
Authors: Labbé A. , Delcros B. , Déchelotte P. , Nouailles C. , Grizard G.
Published: October 2009

The specific binding capacities for human prolactin (hPRL) and human growth hormone (hGH) were examined in human lung membrane preparations at different developmental stages. A parallel study was carried out on rabbit lung preparations to compare binding parameters. Lung tissues were obtained from 15 fetuses of 16–38 weeks after spontaneous or therapeutic abortion and from 7 adults (lobar resection surgery). A histological study was systematically performed with a radial alveolar count in the fetuses with suspected hypoplasia. Binding analysis was performed on both intact membrane preparations and MgCl2-treated membranes, using [125I]hGH and [125I]hPRL as tracers. In the rabbit lung, specific [125I]hGH binding was found. Scatchard analysis revealed a single class of binding sites (affinity constant: 2.6 ± 0.8 × 109 l/nmol and number of binding sites: 9.5 ± 4.3 fmol/mg protein for adult rabbit; 1.85 ± 0.5 × 109 l/nmol and 27.6 ± 3.0 fmol/mg protein for 25-day-old rabbit fetuses, respectively). In contrast, [125I]hPRL did not specifically bind to lung membrane preparations. In the human lung, no consistent specific binding sites for [125I]hPRL or [125I]hGH (< 0.5 %/mg protein) were detected in adults and in 11 of the 15 fetuses. In 4 fetuses, little specific binding was observed (0.59-1.9%/mg protein) for [125I]hGH and (1.5%/mg protein) for [125I]hPRL. There was no correlation with histological lung structure. Our findings confirm the presence of specific binding sites for GH in the adult rabbit lung and demonstrate such binding in the fetal rabbit lung. In contrast, our results showed no significant binding for PRL and GH in the human lung, suggesting that these hormones do not play a direct physiological role in human lung growth and maturation.
Postnatal Development of Pyruvate Oxidation in Quadriceps Muscle of the Rat
Authors: Sperl W. , Sengers R.C.A. , Trijbels J.M.F. , Ruitenbeek W. , De Graaf R. , Ter Laak H. , Van Lith T. , Kerkhoff C. , Janssen A.
Published: October 2009

In order to evaluate the age dependency of enzymes involved in the energy-generating system, skeletal muscle specimens from rats of different ages were investigated for several mitochondrial enzymes. [l-14C]pyruvate ( ± ADP) oxidation rates and pyruvate dehydrogenase complex (PDHC) activity increased significantly from low early values during the neonatal period to nearly adult values at the end of the suckling period. Other enzymes of the pyruvate oxidation route such as citrate synthase and cytochrome c oxidase showed similar patterns of development. Immunoblot studies of PDHC detected a clear increase in the intensity of the bands of the alpha subunits of E1 (pyruvate dehydrogenase) and E2 (dihydrolipoyl transacetylase) within the first 3 weeks of life. The ratio between the individual PDHC proteins indicated that E1α, the regulatory subunit of the multienzyme complex, is the most rapidly increasing protein with age.
Interactive Ventilatory Effects of Two Respiratory Stimulants, Caffeine and Doxapram, in Newborn Lambs
Authors: Bairam Aida , Blanchard Pierre W. , Bureau Michel A. , Laudignon Nicole , Cote Aurore , Aranda Jacob V.
Published: October 2009

Caffeine and doxapram are two respiratory stimulants used in the treatment of apnea in newborns. When used concurrently, these drugs may produce interactive effects on the control of breathing in the newborn. The ventilatory effects of these drugs, given alone or together, were measured during 150 min of drug infusion in two groups of awake lambs 2-5 days old. The first group (n = 5) received a caffeine loading dose of 10 mg/kg followed by a maintenance dose of 0.1 mg/kg/h and incremental doses of doxapram: 0.25, 0.5, 1.25 and 2.5 mg/kg/30 min. The second group (n = 5) received a doxapram loading dose of 5.5 mg/kg followed by a maintenance dose of 1 mg/kg/h and incremental doses of caffeine: 2.5, 5.0, 7.5 and 10.0 mg/kg/30min. In the first group, ventilation increased after the caffeine loading dose from 566 ± 55 to 680 ± 74 ml/kg/min (plasma caffeine = 14.7 ± 1.6 mg/l) and progressively increased with the addition of incremental doses of doxapram upto 1,000 ± 108 ml/kg/min at 2.5 mg/kg of doxapram (p < 0.001 compared to baseline and caffeine loading dose). In contrast, in the second group, the doxapram loading dose markedly increased ventilation from 582 ± 50 to 936 ± 75 (p < 0.002 and p < 0.04 compared to caffeine loading dose) at plasma doxapram of 5.3 ± 0.8 mg/l, but incremental doses of caffeine had no effects. We conclude that doxapram exerts a brisk and powerful respiratory stimulant effect and produces an additional dose-dependent ventilatory response when added to caffeine.
Adrenal Function in Preterm Infants
Authors: Honour J.H. , Wickramaratne K. , Valman H.B.
Published: October 2009

The adrenal function of 10 preterm infants of gestational age 27–34 weeks was assessed longitudinally from measurements of excretion rates of steroid metabolites in 24-hour urine samples collected at frequent intervals for up to 80 days after delivery. The changes in steroid excretion with time in preterm infants of gestation over 28 weeks reflect involution of the fetal adrenal zone at a similar rate to term infants. These findings are consistent with the removal at birth of the inhibitory effects of oestrogen on the 3β-hydroxysteroid dehydrogenase enzyme. The continued function of the adrenal fetal zone beyond the first month in preterm infants of less than 28 weeks gestation may however be due to persistence of some other fetal regulatory adrenal mechanism.
Nutrient Levels in Amniotic Fluid from Women with Normal and Neural Tube Defect Pregnancies
Authors: Weekes E.W. , Tamura T. , Davis R.O. , Birch R. , Vaughn W.H. , Franklin J.C. , Barganier C. , Cosper P. , Finley S.C. , Finley W.H.
Published: October 2009

We analyzed nutrient levels in amniotic fluid obtained during the second trimester of normal, uncomplicated pregnancies from 221 women who delivered apparently healthy infants and from 8 with neural tube defect (NTD) pregnancies. Folate was measured by microbiological assay, vitamin B12 by a radiobinding method, and zinc, copper and iron by atomic absorption spectrophotometry. We found that the mean amniotic fluid nutrient levels of normal pregnancies were 24.7nmol/l for folate, 600pmol/l for vitamin B12, and 1.7, 1.9, and 9.0 μmol/l for zinc, copper and iron, respectively. Amniotic fluid folate, zinc, copper and iron levels of NTD pregnancies were similar to those found during normal pregnancy, however, vitamin B12 levels were markedly lower than those of normal pregnancies.
Hyperglycemia and the Rate of Lactic Acid Accumulation during Cerebral Ischemia in Developing Animals: In vivo Proton MRS Study
Authors: Young Richard S.K. , Petroff Ognen A.C. , Aquila William J. , Cheung Ada , Gore John C.
Published: October 2009

During cerebral ischemia, hyperglycemia has a deleterious effect upon the adult brain but not the neonatal brain. This phenomenon may be related to the fact that hyperglycemia in adult animals subjected to cerebral ischemia raises the ischemic accumulation of lactate by as much as 10-fold. The purpose of this study was to determine whether hyperglycemia during cerebral ischemia produces a similar increase in the rate of lactic acid accumulation in developing animals. Data from in vivo proton magnetic resonance spectroscopic experiments showed that blood glucose concentration did not affect the rate of lactic acid accumulation during cerebral ischemia in either the neonatal dog or juvenile rabbit. The lack of increase in the ischemic rate of lactic acid accumulation during hyperglycemia in the developing animal contrasts sharply with the marked effect of blood glucose concentration upon the rate of lactic acid accumulation in the adult animal. Differences in the total amount of lactic acid formed and the rate at which it is accumulated may contribute, in part, to the greater tolerance of the young animal to cerebral ischemia.
Assay for Opsonin Activity Based on Chemiluminescence of a Cypiridina Luciferin Analog
Authors: Nishida Akira , Kimura Hirokazu , Nakano Minoru
Published: October 2009

Opsonin activity (OA) was investigated in serum samples from cord blood of 11 full-term newborn infants and 12 healthy adult volunteers by the method of luminol-dependent chemiluminescence (L-CL) and Cypiridina luciferin analog-dependent chemiluminescence (CLA-CL) together with the measurement of complement components (C3, C4, C3A and properdin). CL and complement components of cord samples were significantly lower than that of healthy adult blood. CLA-CL showed a significant correlationship to C3 and C3A. L-CL also displayed a significant correlationship to C3A but the relationship to C3 was not significant. From these results, when OA is measured by CL, CLA-CL is preferred to L-CL as a technique.
Intrauterine Brain Damage in Nonimmune Hydrops Fetalis
Authors: Larroche J.C. , Aubry M.C. , Narcy F.
Published: October 2009

Nonimmune hydrops fetalis has been described in a large number of pathological conditions, but brain aspect has been poorly explored. We report the neuropathological findings in a series of 38 fetuses and neonates with anasarca of various origin. Fourteen fetal cerebral ultrasonograms were available; 8 presented some abnormalities. On brain examination, 23 cases showed hypoxic-ischemic lesions. The white matter was the main site of damage that consisted in classical leucomalacia or other features such as: astrocytic glial reaction, micro-calcifications and microthromboses either as isolated finding or in association. Anoxic neuronal damage was much less frequent. Anemia, hypoprotidemia and cardiac failure with hypotension, which often occur in hydrops fetalis, may account for brain perfusion failure and hypoxic-ischemic changes.
Sympathoadrenal Activity in Preterm Infants during the First Five Days of Life
Authors: Ekblad H. , Kero P. , Korvenranta H. , Scheinin M.
Published: October 2009

We measured plasma concentrations of epinephrine (E), norepinephrine (NE), 3,4-dihydroxyphenylacetic acid (DOPAC), and 3,4-dihydroxyphenylglycol (DHPG) as well as urinary concentrations of metanephrine (M), normetanephrine (NM) and 3-methoxy-4-hydroxymandelie acid (MOMA) on day 2 and day 5 in preterm infants; gestational age < 30 weeks (G < 30; n = 16) and gestational age 30-34 weeks (G 30–34; n = 19). Concentrations of E (0.00-2.28 nmol/l) and NE (0.6-9.1 nmol/l) in plasma were much lower than those previously reported during preterm and term delivery. The E:NE ratio decreased from 1:10 on day 2 to 1:30 on day 5, and the M:NM ratio decreased from 1:4 on day 2 to 1:8 on day 5, indicating relatively higher catecholamine secretion from the adrenals than from the sympathetic nerve terminals in preterm infants during postnatal adaptation. Plasma concentrations of DOPAC and DHPG were significantly higher in G < 30 than in G 30–34 (DOPAC, p = 0.0494; DHPG, p = 0.0092), probably relating to a low urinary excretion rate of catecholamine metabolites in infants in G < 30. Plasma and urinary concentrations of catecholamines and their metabolites varied considerably, and no significant correlations to postnatal events could be demonstrated.
Levels of Epidermal Growth Factor in Human Cord Blood
Authors: Ichiba Hiroyuki , Fujimura Masanori , Takeuchi Toru
Published: October 2009

Levels of epidermal growth factor (EGF) in the cord serum of 13 full-term and 84 preterm infants were measured using a radioimmunoassay. Detectable levels of immunoreactive EGF were present in the cord blood at 23 weeks gestation and rose gradually with increasing gestational age. EGF levels correlated significantly with birth weight and placental weight. In small-for-gestational-age infants with birth weights smaller than 3 SD below the mean, EGF levels were lower than those in appropriate-for-gestational-age infants. These results suggest that EGF may play a role in fetal growth, but low EGF levels may also be the result of growth retardation.
Renal Function in Preterm Infants during the First Five Days of Life: Influence of Maturation and Early Colloid Treatment
Authors: Ekblad H. , Kero P. , Korvenranta H.
Published: October 2009

We measured the influence of maturation and early freshly frozen plasma infusion (FFP) on renal function (day 2 and day 5) in preterm infants in intensive care; they were divided into two groups, those with gestational ages < 30 weeks (G < 30) and those with gestational ages of 30–34 weeks (G 30–34). A total of 35 infants was studied. The infants were randomly assigned to one of two treatment groups, one receiving FFP, the other not, yielding four study groups; G < 30 and no FFP (8 infants), G < 30 and FFP (8 infants), G 30–34 and no FFP (9 infants) and G 30–34 and FFP (10 infants). The infants in the two FFP groups received FFP 10 ml/kg on days 1–3. FFP did not significantly influence creatinine clearance (Ccr) or the urinary sodium excretion rate either in G < 30 or G 30–34. CCr was significantly lower (p < 0.001) and fractional urinary sodium excretion significantly higher (p < 0.002) in infants of G < 30 than in infants of G 30–34. Infants of G < 30 had significantly higher plasma potassium concentrations (p < 0.01) than infants of G 30–34. Despite the low CCr and the high urinary sodium excretion rate, infants of G < 30 had stable fluid and electrolyte balance.
Glucocorticoids and the Development of Neuronal Function: Effects of Prenatal Dexamethasone Exposure on Central Noradrenergic Activity
Authors: Slotkin T.A. , Lappi S.E. , McCook E.C. , Tayyeb M.I. , Eylers J.P. , Seidler F.J.
Published: October 2009

Although glucocorticoids slow the development of most cell types, they have been hypothesized to promote the differentiation of catecholaminergic cells. In the current study, pregnant rats were given dexamethasone on gestational days 17, 18 and 19, and the functional state of noradrenergic synaptic activity was assessed throughout postnatal development by measurements of transmitter levels and turnover, and receptor binding capabilities. Despite growth inhibition caused by dexamethasone, the steroid treatment had little or no effect on transmitter levels or receptor binding and accelerated the maturation of norepinephrine turnover in a regionally selective manner. Effects were most notable in the midbrain and brainstem, where turnover rose to maximum levels 1–2 weeks in advance of controls. Turnover also leveled off prematurely in the dexamethasone group, leading to deficits in the postweaning period and into young adulthood. Although similar patterns were obtained in other, later-developing regions, the effects were less consistent and robust; the smaller effects also extended to dopamine turnover. These results suggest that glucocorticoids have a specific promotional effect on the development of central catecholaminergic activity and that administration of exogenous steroids during critical periods of development can lead to lasting functional abnormalities.
Energy Expenditure in Premature Newborns with Bronchopulmonary Dysplasia
Authors: de Gamarra E.
Published: October 2009

Five premature newborns (birth weight, mean ± SD, 960 ± 145 g; gestational age 28 ± 1 weeks) with bronchopulmonary dysplasia (BPD) according to the criteria of Bancalari, and 6 controls (birth weight 1,320 ± 210 g; gestational age 30 ± 2 weeks) were studied for energy expenditure (EE) by indirect calorimetry. The measurement of total EE was performed when the intake of the infants in both groups was the same and when the respiratory condition had stabilized (control group: postnatal age 31 ± 6 days, 1,950 ± 200 g; BPD group: postnatal age 105 ± 45, postnatal weight 2,440 ± 380). The BPD group had a higher VO2 (11.15 vs. 8.04 ml/kg/min, p < 0.01), VCO2 (9.13 vs. 7.74 ml/kg/min, p < 0.02) and total EE (76 vs. 61 kcal/kg/day, p < 0.02). The highest values were encountered in the 3 more severely ill infants: mean VO2 11.03 ml/kg/min, mean EE 82 kcal/kg/min. In these cases, administration of medium chain triglycerides limits the increase in VCO2 and lowers the respiratory quotient (0.87 vs. 0.96 in controls).
Phototherapy for ABO Haemolytic Hyperbilirubinaemia
Authors: Tan K.L. , Lim G.C. , Boey K.W.
Published: October 2009

The efficacy of ‘standard’ daylight phototherapy and ‘high intensity’ blue light phototherapy for neonatal jaundice from ABO-HD, or of a non-haemolytic nature was evaluated. Altogether 77 full-term infants with ABO-HD and 3,020 with non-haemolytic jaundice were studied. Both groups of infants responded well to standard daylight phototherapy; the response in non-haemolytic hyperbilirubinaemia was significantly greater. High intensity blue light phototherapy was significantly more effective in reducing bilirubin levels than standard daylight phototherapy in both groups of infants with no failure being encountered. Four infants with non-haemolytic jaundice did not respond adequately to white light (1.4/1,000); they needed high intensity blue light for adequate response. Bilirubin rebound was mild. Four infants in the blue light group needed a second exposure (28.3/1,000) compared with 20 in the white light group (6.9/1,000), a difference that was significant. Standard white light phototherapy is usually adequate for ABO-HD as well as non-haemolytic hyperbilirubinaemia. High intensity blue light would be preferable where a more rapid and greater response is desirable.
Splanchnic Blood Flow, Oxygen Delivery and Oxygen Consumption in Hypotensive Newborn Piglets
Authors: Cronin Catherine M. , Milley Ross
Published: October 2009

To investigate the relationship between splanchnic visceral oxygen supply and consumption, we altered O2 delivery by decreasing gastrointestinal blood flow during hypotension, and examined the effect on splanchnic oxygen consumption and extraction. We used 10 anesthetized newborn piglets, and measured blood flow using radioactive microspheres. Blood flow fell as perfusion pressure fell in all splanchnic organs, the correlation being most marked in the small intestine. Oxygen consumption was linearly related to blood pressure, and despite a rise in splanchnic oxygen extraction with low blood pressure, splanchnic oxygen consumption was highly dependent on oxygen delivery when oxygen delivery was below a critical value of 0.17 ± 0.05 mmol/100 g/min. We conclude that the newborn piglet gut is incapable of maintaining a constant oxygen supply during the low-flow state produced by hypotension.
Changes in Argininosuccinate Lyase Gene Expression in the Rat Liver during Development
Authors: Benamar M. , Gautier C. , Renouf S. , Fairand A. , Husson A.
Published: October 2009

Expression of the hepatic enzyme argininosuccinate lyase (ASL), one of the urea cycle enzymes, was analyzed during the perinatal period in the rat. To this end, ASL was purified, an ELISA assay was established to quantify the enzyme protein and a cDNA clone was used to measure the amount of specific mRNA in the liver in various stages of development. During the last few days of fetal life, both enzyme and hybridizable RNA were present at levels far below those measured in the fully differentiated adult liver. Just after birth, they increased rapidly and the mRNA accumulation, particularly, could result from an enhanced rate of transcription as suggested by the experiment with actinomycin D. This postnatal shift in ASL expression was also linked to adrenal activation at birth, as shown by adrenalectomy. However, the extent to which the ASL protein accumulated after birth appeared to be limited when compared to mRNA accumulation, suggesting control mechanisms at the translational level. Thus, during the perinatal period of the rat, both transcriptional and translational control might be implicated in the expression of the ASL gene.
Applications of Anti-Curosurf Antibodies to Understanding the Biology of Alveolar Surfactant
Authors: Strayer David S.
Published: October 2009

The structure of surfactant-binding proteins from alveolar cell membranes was investigated using monoclonal anti-idiotypic antibodies directed against surfactant-binding regions of anti-surfactant monoclonal antibodies. Two different series of monoclonal anti-surfactant antibodies were used. One series included antibodies against rabbit surfactant, and the other antibodies against porcine surfactant. In addition, two monoclonal anti-idiotype antibodies were made. These anti-idiotype antibodies, called A2R and A2C, bind both anti-Curosurf and anti-rabbit surfactant antibodies comparably. They recognize a 30-kDa cell membrane protein on alveolar and bronchial epithelial cells. In addition, A2C and A2R block the binding of radiolabeled surfactant to these cells. Using a combination of A2C and A2R cDNA expression libraries from both human and porcine lungs were screened. One independent clone was identified in each library that produced protein that bound these monoclonal antibodies. The protein encoded by the cDNA in each clone bound radiolabeled recombinant surfactant protein-A. It is concluded that human and porcine alveolar cell SP-A binding proteins have been identified and its cDNA cloned. The potential implications of this finding for the understanding and treatment of surfactant deficiency states are considerable.