ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

The mechanisms underlying failure in sudden infant death syndrome may involve inadequate compensatory motor responses to a hypotensive challenge; the insult may result from a shock-like sequence, or from a ventilatory challenge that leads to a hypotensive event. Structures ordinarily not considered in mediating breathing or cardiovascular control, especially cerebellar-related structures, may play a critical role in compensatory responses, and underlie the position-dependent risk for SIDS. Dysfunction in affected brain areas appears to arise prenatally from a compromised fetal environment, with a nicotinic component contributing to the deficient mechanism.Physiologic characteristics of infants who later succumb to SIDS, and cardiovascular events associated with the fatal scenario suggest a failure of interaction between somatomotor and autonomic control mechanisms in infants at risk for the syndrome. A failure of compensatory motor actions to overcome a profound hypotension, perhaps mediated by cerebellar mechanisms that regulate blood pressure, may underlie the fatal event.

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Most mitochondrial DNA (mtDNA) alterations associated with human disorders are heteroplasmic,i.e.mutant mtDNA molecules coexist with normal ones within the cell. We addressed the possibility of intermitochondrial exchanges through histologic analyses of cybrid clones with increasing proportion of the MELAS (A3243G) mtDNA transfer RNA point mutation. MtDNA-dependent cytochromecoxidase activity and protein composition as well as mitochondrial membrane potential appeared heterogeneous in individual cells from clonal heteroplasmic cell populations on the basis of confocal and electron microscopy. The number of defective cells increased with increasing mutation load. We conclude that in the presence of a heteroplasmic mtDNA mutation in the cell type that we studied, intermitochondrial molecular exchanges cannot provide an efficient even distribution of the complementing molecules such as wild-type mtDNA, transfer RNA, or protein. Mitochondria in these heteroplasmic cells cannot, therefore, be considered a single functional unit.

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency is an autosomal recessive disorder of mitochondrial fatty acid oxidation. Apart from life-threatening metabolic derangement with hypoketotic hypoglycemia, patients often show liver disease, cardiomyopathy, and neuropathy. A common mutation (1528G>C) in the gene coding for the &agr;-subunit of the mitochondrial trifunctional protein harboring LCHAD activity is found in 87% of the alleles of patients. LCHAD is considered a rare disorder with only 63 patients reported in the literature. Whether this is due to a truly low prevalence of the disorder or because many patients remain unrecognized as a result of aspecific symptomatology is not clear. A remarkable association between LCHAD deficiency and the hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome, which is a severe complication of pregnancy, has been reported. Because of this, we studied the frequency of the common LCHAD mutation in the Dutch population by analyzing 2047 Guthrie cards and 113 women who had suffered from HELLP syndrome. To be able to perform this large-scale study in dried bloodspots, we developed a new sensitive PCR-restriction fragment length polymorphism method. The carrier frequency for the common LCHAD mutation in the Dutch population was found to be low (1:680), consistent with the observed low incidence of the disorder. In the group of women with a history of HELLP syndrome, the prevalence of the common LCHAD mutation was also low (1:113). We conclude that LCHAD deficiency is, indeed, a rare disorder and that heterozygosity for the common mutation is not a major cause of the HELLP syndrome.

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Dexamethasone is used commonly in the treatment of chronic lung disease of prematurity, but there are concerns about possible deleterious effects on growth and bone. Our aim in this study was to examine the effects of dexamethasone treatment on bone and collagen turnover in preterm infants. Bone-specific alkaline phosphatase, the C-terminal propeptide of type I collagen (PICP, reflecting whole-body type I collagen synthesis), and the N-terminal propeptide of type III procollagen (P3NP, reflecting soft tissue collagen turnover), together with the C-terminal telopeptide of type I collagen (ICTP), urinary pyridinoline (Pyd), and deoxypyridinoline (all markers of collagen breakdown) were measured at weekly intervals over the first 12 wk of life in 14 preterm infants with chronic lung disease treated with dexamethasone. Results were expressed as SD scores relative to preterm control infants not treated with dexamethasone. PICP, P3NP, ICTP, and Pyd all showed marked decreases (−2.1 to −3.7 SD scores) during the first week of treatment (p< 0.001), returning to pretreatment levels after stopping dexamethasone. In the group as a whole, these collagen markers were negatively correlated with dexamethasone dose (p< 0.0001); negative correlations were also seen in most individual babies, although the slopes of individual regression lines varied by a factor of 2. Weight gain at 12 wk was correlated with PICP, expressed as the mean SD score over 12 wk for each baby, (r= 0.69,p< 0.01) but not with other markers or cumulative dose of dexamethasone. We conclude that dexamethasone markedly suppressed collagen turnover in preterm infants in a dose-dependent fashion, although some babies were more affected than others. The degree of suppression of type I collagen synthesis was a strong independent predictor of overall weight gain over the first 12 wk of life.

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Children with inflammatory bowel disease are known to be at risk of osteopenia. The cause of this osteopenia is likely to be multifactorial, but the inflammatory process with its characteristic overproduction of cytokines has been implicated. To investigate this possible contribution of the disease activity to the development of osteopenia, we performedin vitroassays of the proliferation of osteoblast-like cells of differing origins in response to the inflammatory cytokines tumor necrosis factor-&agr; and IL-1&bgr;. Osteoblast-like cells derived from pediatric bone explants, adherent stromal cells derived from bone marrow (osteoprogenitors), MG-63 osteosarcoma cells, and SV-40 virally transformed osteoprogenitor cells (HCC1) were studied. Tumor necrosis factor-&agr; stimulated the proliferation of cells in primary cultures(i.e.from explants and marrow samples) in a linear, dose-dependent manner. In contrast, inhibition of proliferation was observed with the established cell lines (MG-63 and HCC1). IL-1&bgr; stimulated proliferation of all cells apart from the immortalized human bone marrow cell line, HCC1, in which case potent inhibition was observed. We conclude that proinflammatory cytokines are potent regulators of osteoblast-like cell proliferation, and that the responses are specific to cell type. The opposite results obtained with established cell lines compared with the primary cultures suggest that careful consideration should be given to choosing the most suitable cell line forin vitrostudies relating toin vivomechanisms predisposing to osteopenia.

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Intrauterine growth retardation and diabetes mellitus during human gestation result in significant losses of fetal and neonatal brain iron. Brain iron deficiency is associated with impaired cognitive processes including memory and attention. The regional distribution of iron staining and cytochromecoxidase (CytOx) activity have not been mapped in the iron-sufficient or -deficient neonatal rat. CytOx is the iron-containing terminal enzyme in oxidative phosphorylation; its activity reflects neuronal metabolism. We hypothesized that neonatal brain iron deficiency differentially decreases iron and CytOx activity in brain regions, with more pronounced losses in structures involved in recognition memory. Pregnant Sprague Dawley rats were fed either an iron-deficient or -fortified diet from gestational d 1 until postnatal d 10. Iron staining and CytOx activity of 20 brain structures were mapped histochemically in 25 rats from each group. Brain iron staining was reduced from 75% to 100% and CytOx staining was decreased from 0% to 42% in the iron-deficient group (p< 0.001). Areas with significantly reduced CytOx activity (p< 0.001) included all measured subareas of the hippocampus (CA1: 42%, CA3ab: 34%, CA3c: 33%, and dentate gyrus: 32%), the piriform cortex (17%), the medial dorsal thalamic nucleus (28%), and the cingulate cortex (41%). In contrast, the anterior thalamic nucleus, the lateral amygdaloid nucleus, and the medial habenula, areas not involved in higher cognitive functions, did not have significantly reduced CytOx activity (0%, 10%, and 16%, respectively). We conclude that perinatal iron deficiency differentially reduces neuronal metabolic activity, specifically targeting areas of the brain involved in memory processing.

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Maternal caffeine intake has been suggested to influence the offspring. We have studied the effects of maternal caffeine intake on adenosine and GABA receptors, targets for caffeine, during development of the rat brain. Caffeine (0.3 g/L) was added to the drinking water of rat dams during pregnancy and early postnatal life. Adenosine A1and A2Aand GABAAreceptor development was studied using receptor autoradiography andin situhybridization. Pups were examined on embryonic d 14 (E14), E18, E21, 2 h after birth (P2h), P24h, postnatal d 3 (P3), P7, P14, and P21. Adenosine A1receptor mRNA was detected at E14 and receptors at E18. A1mRNA levels increased from the level reached at E18 between P3 and P14 (maximally a doubling), whereas A1receptors, studied by [3H]-1,3-dipropyl-8-cyclopentyl xanthine binding, increased later and to a much larger extent (about 10-fold) postnatally. Caffeine treatment had no significant effect on adenosine A1receptors or on A1receptor mRNA. A2AmRNA had reached adult levels by E18, whereas receptor levels were low or undetectable before birth and increased dramatically until P14. Caffeine did not influence A2Areceptors or A2Areceptor mRNA at any stage during development. [3H]-flunitrazepam binding, representing GABAAreceptors, showed large regional variations during ontogeny, but there were no clear differences between the caffeine-exposed and the nonexposed pups. Thus, exposure to a low dose of caffeine during gestation and postnatal life had only minor effects on development of adenosine A1and A2Areceptors and GABAAreceptors in the rat brain.

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID