摘要:

Neonates with septicemia tend to develop granulocytopenia, which may, in part, be due to septic mediators such as oxygen free radicals and tumor necrosis factor alpha (TNF-&agr;). Granulocytopenia may be caused by a decrease in granulocyte growth and/or an increase in granulocyte destruction. In the present study, we investigated antioxidant regulation of endotoxin-modulated neonatal granulopoiesis and granulocyte apoptosis. Using human umbilical cord blood (HUCB), we found that simulating endotoxemiain vitroelicited significant superoxide production within a few minutes. Endotoxin exposure suppressed colony-forming unit–granulocyte and monocyte formation in a dose-dependent fashion. Addition of antioxidants such as N-acetyl-cysteine could reverse the endotoxin suppression of colony-forming unit–granulocyte and monocyte formation (13 ± 5versus75 ± 5 colony-forming units/mL). Spontaneousin vitrogranulocyte apoptosis in 6 h, as reflected by phosphatidylserine expression on the cell surface, was higher in granulocytes from HUCB than in those from adult blood (10.8 ± 1.0%versus5.6 ± 1.2%). The addition of endotoxin or IL-8 to the cells in thein vitromodel did not promote granulocyte apoptosis, but TNF-&agr;, a major mediator of the effects of endotoxin, significantly induced granulocyte apoptosis in HUCB (controlversusTNF-&agr;: 8.9 ± 1.2%versus35.9 ± 2.9%). Addition of the antioxidant N-acetyl-cysteine effectively blocked TNF-&agr;-induced granulocyte apoptosis as demonstrated by DNA fragmentation. Results from these studies indicate that oxygen radicals are directly involved in endotoxin suppression of granulopoiesis, and indirectly promote granulocyte apoptosis, presumably through TNF-&agr;-mediated action. Thus, under certain conditions, modulation of oxygen radical production in the blood may benefit neonates with granulocytopenia.

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Because docosahexaenoic acid (DHA) may be an essential nutrient for the visual and early cognitive development of preterm infants, DHA enrichment of preterm formulas has been recommended. This randomized trial was designed to study the n-6 and n-3 fatty acid status of healthy preterm infants fed a formula enriched with a low eicosapentaenoic-fish oil until 4 mo corrected age compared with that of infants fed a standard formula. A reference group of breast-fed infants was studied concurrently. The fatty acid content of red blood cell (RBC) phospholipid was assessed at enrollment, hospital discharge, expected term, and 3 and 6 mo postterm. The DHA content of RBC phospholipid was higher in infants fed the enrichedversusthe standard formula at hospital discharge, expected term, and 3 and 6 mo postterm. However, compared with infants fed the standard formula, infants fed the enriched formula had also higher RBC phospholipid eicosapentaenoic content (0.69 ± 0.15%versus0.25 ± 0.12%,p< 0.001), and lower RBC phospholipid arachidonic acid content (15.1 ± 0.93%versus18.8 ± 0.89%;p< 0.001). We conclude that supplementing preterm infants with low-eicosapentaenoic fish oil is effective in improving DHA status, but results in worsening of n-6 fatty acid status. We speculate that preterm infants may require a dietary supply of arachidonic acid as well as DHA if the same fatty acid status as that of breast-fed infants is to be achieved.

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Chinese hamster ovary cultured cells were transformed to continuously express wild-type and two mutant ornithine transcarbamylase genes, R141Q and R40H. In addition, these cells were transfected to transiently express the same genes. The R141Q mutation abolishes the enzymatic activity, and the amount of “mature” protein present in transfected cells is equivalent to the wild type. The R40H mutation causes a reduction of enzymatic activity to approximately 26 to 35% of wild type concomitant with a significant reduction in the amount of protein present. Transfection with wild-type and mutant genes together in various proportions did not reveal dominant negative effects of the two mutations studied. This expression system can be used to examine the deleterious effect of private mutations or lack thereof in families with ornithine transcarbamylase deficiency as well as evaluate the potential dominant negative effects of gene delivery for treatment of ornithine transcarbamylase deficiency.

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

In developing mammals, we and others demonstrated that sulfation is an important pathway in the metabolism of thyroid hormone, and there is significant fetal-maternal transfer of sulfated iodothyronine. In the present study, we characterized a novel iodothyronine sulfotransferase (IST) in pregnant rat uterus.125I-labeled 3,3′-diiodothyronine (T2), T3, rT3, and T4were used as substrates with unlabeled 3′-phosphoadenosine-5′-phosphosulfate (PAPS) as the sulfate donor. Sulfated iodothyronine products were separated by Sephadex LH-20 column and further identified on reverse phase HPLC. We measured IST activity in pregnant rat uterus by incubating 1 &mgr;M substrate, 50 &mgr;M PAPS, and 50 &mgr;g cytosol protein, pH 7.2, 30 min at 37°C. The results show that the substrate preference of the uterine IST activity is: T2> rT3> T3> T4; the pH optimum is 6.0 for T2. The KmandVmax(for gestational day 21 uterus) for T2are 0.62 &mgr;M and 3466 pmol/mg protein/h, respectively; for PAPS the values are 2.6 &mgr;M and 1523 pmol/mg protein/h, respectively. During pregnancy, the total activities exhibit a U-shaped curve with minimum activity at day 13 of gestation; while a thermostable activity increases significantly near term. In summary, there is significant uterine IST that varies during pregnancy. The role of this uterine sulfotransferase activities in regulating the bioavailability of thyroid hormone in the developing fetus remains to be elucidated.

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

We report a novel inborn error of metabolism identified in a child with an unusual neurodegenerative disease. The male patient was born at term and recovered well from a postnatal episode of metabolic decompensation and lactic acidosis. Psychomotor development in the first year of life was only moderately delayed. After 14 mo of age, there was progressive loss of mental and motor skills; at 2 years of age, he was severely retarded with marked restlessness, choreoathetoid movements, absence of directed hand movements, marked hypotonia and little reaction to external stimuli. Notable laboratory findings included marked elevations of urinary 2-methyl-3-hydroxybutyrate and tiglylglycine without elevation of 2-methylacetoacetate, mild elevations of lactate in CSF and blood, and a slightly abnormal acylcarnitine profile. These abnormalities became more apparent after isoleucine challenge. Enzyme studies showed absent activity of 2-methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) in the mitochondrial oxidation of 2-methyl branched-chain fatty acids and isoleucine. Under dietary isoleucine restriction, neurologic symptoms stabilized over the next 7 months.

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID