摘要:

ABSTRACTSWe have recently demonstrated that serum concentration of 3,5,3‘-triiodothyronine sulfate (T3S) is markedly elevated in the human newborn at a time when serum 3,5,3’-triiodothyronine (T3) is very low. The present study explores the ability of maternal (19–21 d pregnant) and near-term fetal Sprague-Dawley rat tissues to 1) monodeiodinate T3S and T3in both the outer and the inner ring and 2) desulfate T3S to T3. Maternal liver microsomes metabolized T3S exceedingly efficiently (compare fetusp< 0.05). Eighty percent or more of T3S was consumed during its incubation with 360 μg/mL microsomes for 2 h. The majority of the consumption of T3S by adult liver microsomes occurred by its 5‘-monodeiodination to 1; little inner-ring monodeiodination to 3,3’-diiodothyronine was demonstrable. In fetal liver microsomes, however, over 75% of the substrate T3S remained unchanged after a 2-h incubation. T3was metabolized similarly moderately by fetal and maternzl liver microsomes. Brain microsomes metabolized T3S poorly in both the mother and the fetus. Over 90% of substrate T3S remaned unchanged after a 2-h incubation in each case. Interestingly, brain microsomes metabolized T3more rapidly than T3S (p< 0.05). In the fetus, desulfation of T3S to T3was clearly evident only in microsoms from the liver and the brain; in the adult, it was plentiful in many tissues. Fetal liver and brain tissues metabolize T3S poorly, and both actively desulfate T3S to T3. These data and those indicating high serum T3S in the fetus suggest that T3S is a local source of T3in critical tissues in the fetus and possibly in adults with the low T3syndrome. (Pediatr Res31: 541–544, 1992)

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

ABSTRACTSTo determine the sensitivity and specificity of detecting urinary medium-chain acylearnitines for the diagnosis of MCAD deficiency, 114 urine specimens from 75 children with metabolic diseases and controls were analyzed in a blinded fashion using a radioisotopic ex-change/HPLC method. All 47 patients with MCAD deficiency were correctly diagnosed using the criterion hexanoylcarnitine or octanoylcarnitine peak areas larger than those of other medium-chain acylcarnitines. The majority of them were tested during the asymptomatic state without L-carnitine loading. Four patients with other defects of fatty acid oxidation and three patients receiving vatproic acid had a similar acylcarnitine exeretion pattern. To farther examine the specificity of the method, eight infants receiving a diet enriched with medium-chain triglycerides and 13 additional patients receiving valproic acid were studied. Most of these also tested positive for MCAD deficiency by the above criterion. Analysis by a new gas chromatographic-mass spectrometric procedure revealed that octanoylearnite, not valproylcarnitine, was the most abundant medium-chain carnitine ester excreted by a patient treated with valproic acid. Quantitation of urinary hexanoylcarnitine and octanoylcarnitine showed considerable overlap among patients with MCAD deficiency and those receiving valproic acid or a medium-chain triglyceride-enriched diet. MCAD deficiency can be reliably detected in urine specimens by this method without the need for prior carnitine loading. However, other defects in fatty acid oxidation must be differentiated from MCAD deficiency, and a history of medium-chain triglyceride or valproic acid administration must be considered if the diagnosis of MCAD deficiency is sought through analysis of urinary acylcarnitines. (Pediatr Res31: 545–551, 1992)

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

ABSTRACTSBALB/cByJ (J) mice have short-chain acyl-CoA dehydrogenase (SCAD) deficiency and an organic aciduria similar to that of human SCAD deficiency. [9,10(n)-JH)- and [15,16(n)-3H)paimitale oxidations in J mouse fibroblasts were 96 and 35% of control, respectively, consistent with an isolated SCAD defect. Acyl-CoA deby-drogenase activities were assayed in muscle and fibroblast mitochondria from BALB/cBy controls (Y) and SCAD-deficient J mice. Medium-chain acyl-CoA dehydrogenase (MCAD) activities were comparable in both J and Y mice from all tissues. In the presence of MCAD antiserum, SCAD activities in J mice were undetectable in both tissues. Apparent Km and Vmaxvalues in liver mitochondria suggested a somewhat increased affinity of MCAD for butyryl-CoA in J mice, as compared with MCAD from other species. Immunoblot studies using mitochondria revealed identical apparent SCAD molecular weight in liver, muscle, and fibroblasts from Y and mice and no detectable SCAD antigen in J mice; MCAD antigen was detected in comparable amounts from both Y and J mice. Radiolabeling and immunoprecipitation studies in J mouse fibroblasts revealed no SCAD synthesis, but normal MCAD synthesis. These data argue against the existence of tissue-specific SCAD isoforms in the mouse and confirm that this mouse strain is a model for the human organic aciduria resulting from this β-oxidation defect. (Pediatr Res31: 552–556, 1992)

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

ABSTRACTSMitochondrial DNA deletions have been described in the Kearns-Sayre syndrome (KSS) and the Pearson's marrow-pancreas syndrome. In some cases, the same 4 977-bp deletion has been identified in these two very different diseases. Therefore, it is not currently possible to predict the clinical phenotype from the size or location of the deletion. Instead, differential tissue distribution of the deletion has been implicated as one possible determinant of phenotype. In particular, in KSS the deletions have not been detected by Southern blotting in the blood, whereas in Pearson's syndrome they are easily detectable. We describe here an 11-y-old boy with clinically characteristic KSS and a 7.4-kb mitochondrial DNA deletion between aucleotides 7 194 and 14 595. Southern blotting reveals that 75% of the mitochondrial DNA molecules from his peripheral blood have this deletion. This case blurs further the molecular distinction between the KSS and Pearson's marrow-pancreas syndrome, questioning whether tissue distribution is a sufficient explanation for the very different pheaotypes of these disorders. (Pediatr Res31:557–560, 1992)

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

ABSTRACTSThis study was undertaken to identify the extent of involvement of cutaneous and noncutaneous epithelia during expressionin uteroof Junctional epidermolysis bollosa. Skin and other organs from a 19-wk estimated gestational age fetes affected with Junctional epider-molysis bullosa and from age-matched controls were examined by light and transmission electron microscopy. In the affected fetus, skin samples from different body regions including trunk, leg, arm, and finger all showed some separation at the dermal-epidermal junction in the plane of the lamina lucida. Hemidesmosomes were absent or hypoplastic, whereas anchoring fibrils appeared normal in structure and number. Interfollicular epidermis appeared to have separated easily, whereas some follicles remained anchored in the dermis. Areas of epithelium in the trachea and bronchi had separated, but within the lung parenchyma the epithelium of smaller bronchioles and alveoli remained attached to supporting connective tissue. The transitional epithelium of the urinary bladder showed small areas of separation compared with the gall bladder epithelium, which showed extensive separation. Gall bladder epithelium in several control fetuses also was consistently separated. In the affected fetus as well as in controls, gall bladder had multiple layers of basal lamina, a previously unrecognized structural feature of human fetal gall bladder. Epithelia that remained intact included the linings of the stomach and small and large intestines and endothelium of large and small vessels in all organs. Kidney, spleen, liver, and lymph nodes appeared normal in all aspects. In control samples, neither skin nor most of the noncutaneous epithelia had separated from the underlying connective tissue. The epithelial-mesenchymal separations observed in the affected fetus indicate that the abnormality is expressed during fetal development and affects the epithelia of certain internal organs as well as the skin. (Pediotr Res31: 561–566, 1992)

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

ABSTRACTSThe expression of surface tissue factor procoagulant activity and its shedding by blood monocytes can be induced by several stimuli. Few of these defined situations, other than the presence of bacteria and their toxins, are commonly present in the young human infant. In this study, measurements were made of the percentage of monocytes expressing surface tissue factor apoprotein (TFA) in blood taken from babies in the early weeks of life. Mono-nuclear cells were separated from blood in an environment free of detectable endotoxin. After exposure to a polyclonal rabbit antibody raised to purified brain TFA and subsequent exposure to a fluorescin-labeled murine anti-rabbit IgG, the cell fluorescent activity was analyzed by flow cytometry. The percentage of monocytes showing strong fluorescence was determined. In every instance when systemic bacterial infection was present, more than 60% of the monocytes examined showed fluorescence indicative of the presence of surface TFA. In a single case of fungal Candida septicemia, none of the monocytes was positive. More than 60% of cells were found to be positive in certain instances where infection was highly probable but not proven. Positive cells were found in three cases of isoimmune hemolytic disease of the newborn, as had been anticipated from previous studies, whereas less than 25% of monoeytes derived from babies in the absence of discernible infection or isoimmune hemolytic disease expressed surface TFA (p < 0.001). These findings provide insight into a possible mechanism of coagulation activation in sepsis and may prove to be a useful predictor of the presence of infection of endotoxemia in young infants. (Pediatr Res31: 567–573, 1992)

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

ABSTRACTSNewborns are predisposed to neutropenia and thrombocytopenia during bacterial sepsis. The presence of peripheral cytopenias during overwhelming infection may be secondary to decreased bematopoietic growth factor production during states of increased demand. We therefore examined circulating levels of granulocyte-colony stimulating factor (G-CSF) and IL-3, production of G-CSF and IL-3 from unstimulated and stimulated mononuclear cells (MNC), expression of G-CSF and IL-3 genes during unstimulated and stimulated conditions, and equilibrium and binding of G-CSF receptors on mature effector peripheral blood cells of adults and neonates. Serum from cord and adult peripheral blood contained negligible amounts of both G-CSF (<50 pg/mL) and IL-3 (<5 pg/mL). Constitutive supernatant levels of G-CSF and IL-3 from cord and adult unstimulated MNC were also undetectable. However, there was a significant difference in G-CSF and IL-3 production from stimulated cord and adult MNC. Supernatants from stimulated adult MNC had significantly more G-CSF (p < 0.007) and IL-3 (p < 0.02). Additionally, Northern blot hybridization and densitometry of autoradiographs demonstrated significantly more G-CSF and IL-3 mRNA transcripts from adult than from cord MNC. Lastly, affinity, binding, and number of G-CSF receptors on cord and adult peripheral effector cells were equal. These data suggest that, during states of increased demand, cord MNC produce less G-CSF and IL-3 than do adult MNC and have an associated reduction in their respective mRNA transcripts. These findings may have implications in the pathogenesis of neonatal cytopenias during states of increased demand, such as sepsis. (Pediatr Res 31: 574–578, 1992)

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

ABSTRACTSIn this study, we investigated whether capillary plasma catecholamines can be used as a suitable substitute for arterial catecholamines. Analysis was done radioenzymatically. Catecholamine concentrations were not different in arterial and simultaneously collected “arterialized” (warmed foot) capillary plasma obtained by heel-prick from 18 neonatal intensive care patients as assessed by linear regression analysis (correlation coefficient: 0.966 for noradrenaline; 0.894 for adrenaline; p < 0.05) and by a Wilcoxon test [noradrenaline: 2.13 (0.61–10.47)versus2.41 (1.05–10.23); adrenaline: 0.75 (0.16–1.70)versus0.71 (0.10–1.37) nmol/L, median (range)]. However, “arterialization” of capillary blood is important; when blood was obtained in nine neonates without warning their feet, capillary concentrations of noradrenaline were higher than arterial values (p < 0.03) and those of adrenaline were not different from arterial values. Catecholamne concentrations in arterialized capillary plasma collected in healthy full-term infants at 1 h [n = 9; noradrenaline: 6.85 (3.49–8.88) nmol/L; adrenaline: 1.34 (0.86–2.85) nmol/L and 5 d after birth [n = 27; noradrenaline: 1.58 (0.89–3.16) nmol/L; adrenaline: 0.59 (0.25–1.64) nmol/L] reflect the well-known fall (p < 0.01) in catecholamine levels after delivery. With a highly sensitive analytical technique, catecholamine concentrations can reliably be assessed in minute samples (100–200 μL) of arterialized capillary blood, even when concentrations have dropped to low “resting” basal levels. Moreover, the capillary sampling procedure is simple and safe, can easily be applied to healthy infants, and does not have the practical and ethical limitations of arterial blood sampling. (Pediatr Res31: 579–582, 1992)

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

ABSTRACTSWe 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 ± 15versus11 ± 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, radios BMC will “catch-up” to that of similar infants given formula in the posthospitalization period. (Pediatr Res31: 583–586, 1992)

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

ABSTRACTSBecause duodenal motor activity differs between preterm and term infants during fasting, this study evaluated the responses of motor activity and peptide release in response to feeding. In the first study, fasting concentrations of gastrin, gastric inhibitory peptide, neurotensin, and peptide YY (PYY) were determined in 53 preterm and 20 term infants. Plasma concentrations of gastrin and neurotensin were significantly lower in preterm infants than in healthy adults reported previously by our lab (p < 0.01). Plasma concentration of gastric inhibitory peptide and PYY were higher than in healthy adults (p < 0.01). Gastrin concentrations in preterm and term infants varied directly with gestational age (p < 0.005); PYY varied inversely with gestational age (p < 0.005). In a secondary study, intestinal manometry was recorded and serial peptide concentrations were determined in 43 preterm babies who were given their first enteral feeding intraduodenally with formula or sterile water. Although none of the four peptide plasma concentrations changed in response to feeding with water, plasma concentrations of gastric inhibitory peptide, neutrotensin, and PYY significantly increased with formula feedings (p < 0.05 or less). In addition, plasma gastrin increased significantly in seven infants fed milk compared with eight fed water by orogastric tube (p < 0.01). In contrast to the peptide response to feeding, motor activity changed in response to feeding with either water or milk; motility indices increased and periods of motor quiescence decreased significantly during feeding as compared with fasting (p < 0.02). Responses of both motor activity and peptides to feeding were time related. Although fasting concentrations of four regulatory peptides were immature in preterm infants compared with adults, postprandial responses to nutrient feedings were present in the first days of life. This discrepancy in functional maturation of the preterm intestine during fasting and feeding is present for both motor activity and peptide response, and we speculate that the controlling mechanisms of these two phases of digestion may mature independently at different postconceptual ages. (Pediatr Res31: 587–590, 1992)

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID