摘要:

The immaturity of antioxidant capacity in the lung in preterm newborn infants is postulated to contribute to the development of hyperoxic lung injury. Antioxidant enzymes in fetal lung, comprised of copper-zinc (cytosolic) and manganese (mitochondrial) superoxide dismutases, glutathione peroxidase, and catalase, have been reported to increase during the late gestational period. To determine whether such maturation of antioxidant capacity occurs in other tissues, we have evaluated the development of these four enzymes from d 18 to 22 of gestation in rat lung, kidney, and heart. To resolve the confusion in the reported levels of lung superoxide dismutases, the two isoenymes were assayed separately by specific RIA. The growth of the kidney exceeded that of the whole body during this period, while the growth of the lung and heart did not. The concentrations of the four antioxidant enzymes in lung and kidney increased in a stepwise manner during this period, and the magnitude of the change for each enzyme was greater in the kidney than in the lung. On the other hand, the only significant change in the concentrations of heart antioxidant enzymes observed was a mild increase in the glutathione peroxidase concentration from d 20 to 22. These results suggest that the prenatal maturation of antioxidant capacity occurs earlier in the heart and later in the kidney than in the lung, and that the immaturity of antioxidant capacity could make the fetal rat kidney vulnerable to free radical-mediated injury.

ISSN:0031-3998    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

We speculated that there are important age-related differences in the economy of left ventricular force development in the isolated heart. To assess this, we evaluated oxygen consumption and force development in newborn (less than 1 wk old) (n=26), juvenile (4-6 wk old) (n=26), and adult (5-7 mo old) (n=26) isolated, isovolumic rabbit hearts. Measurements were obtained with three different interventions, including 1) changes in heart rate, 2) inotropic stimulation with isoproterenol, and 3) changes in end-diastolic pressure. We found no significant baseline differences in the economy of force development. However, when heart rate was increased by 20%, the force/oxygen consumption ratio (economy) increased in newborn hearts by approximately 37%, whereas there was a decrease in juvenile and adult hearts of ~27%. In addition, with increases in end-diastolic pressure above 10 mm Hg, newborn hearts increased their force/myocardial oxygen consumption ratio to 300% of the baseline value, whereas adults increased to only 160% of baseline. Isoproterenol produced no significant age-related differences in the force/myocardial oxygen consumption ratio. We conclude that there are important age-related differences in the economy of left ventricular force development in this model, but these differences are apparent only at higher heart rates and end-diastolic pressures.

ISSN:0031-3998    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

We examined anatomically the hearts of 198 WKY/NCrj rats of 20 litters. There were 51 rats with moderate to severe thickening of the pulmonary valve and 19 rats with a ventricular septal defect; the two lesions occurred together in 16 rats, in 15 of which there were overriding of the aorta, stenosis of the pulmonary outflow tract, and hypertrophy of the right ventricle, fulfilling the criteria for tetralogy of Fallot in man. The papillary muscle of the conus was absent in 65 rats. The heart was abnormally heavy in 18. We analyzed the relationship between cardiac hypertrophy and valvular lesions and septal defects in these rats plus 27 selected WKY rats with abnormally heavy hearts. Of the 151 rats with neither severe valvular lesions nor septal defects, six rats had abnormally heavy hearts and 67 rats had disproportionate ventricular septal thickening. This situation in the rats is similar to hypertrophic cardiomyopathy. The occurrence of these abnormalities, isolated or in association, in rats of an established inbred strain strongly suggests that they are etiologically or genetically linked, and that the rats should be a useful animal model for these diseases in man.

ISSN:0031-3998    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The IGF-I gene from leukocyte DNA of a control population of normal stature was studied using Southern blotting. Restriction fragment lengths for 21 enzymes were determined and three restriction fragment length polymorphisms (RFLP) were found (EcoRV, HindIII, and PvuII). In addition, the IGF-I gene of 64 constitutionally short subjects, five Pygmies, and 10 constitutionally tall subjects was analyzed. No IGF-I gene alterations were detectable by Southern blot in any of these conditions. Linkage analysis using genetic markers (RFLP) yielded results that were uninformative for five constitutionally short families investigated, owing to the limited number of RFLP and their low incidence (17% for the 5.2- kb HindIII, 5-kb PvuII RFLP alleles, and 13% for the 13- kb EcoRV RFLP allele). The EcoRV RFLP was found to map near Exon 1. The incidence of the 13-kb polymorphic allele with EcoRV proved to be lower (4%) in the group with constitutionally short stature than in controls. These results could suggest that modifications in the region of the IGF-I gene may be involved in constitutionally short subjects.

ISSN:0031-3998    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Menkes' kinky hair syndrome (KHS) is a lethal x-linked neurodegenerative disorder of copper metabolism, with low serum copper concentrations, tissuespecific copper sequestration, and decreased activities of cuproenzymes in a number of cell types. Although liver copper accumulation is abnormal in KHS, the actual defect in hepatic copper metabolism has not been elucidated. Our studies of liver copper metabolism were conducted in the mottled (blotchy) mouse, an animal model of KHS. After implantation of central venous and biliary catheters in both blotchy and control mice, we measured biliary copper excretion, hepatic copper uptake, and tissue copper contents over an 8-h period after i.v. bolus administration of radioactive62Cu. Under the experimental conditions used, bile flow and biliary bile acid excretion were held constant, and control and blotchy hepatic64Cu concentrations were similar in the face of the expected differential in control and mutant kidney64Cu contents. Biliary excretion of radiocopper was 24.7 ± 1.5% of injected64Cu over 8 h in control animals, whereas heterozygotes excreted 6.5 ± 1.3% and a single hemizygote excreted less than 2%. The pattern of biliary copper excretion was different, with sharp increase and steady decline in control biliary64Cu excretion but consistently low excretion in mutant mice. No differences were observed in control or mutant hepatic uptake of64Cu. These data show a reduced biliary excretion of copper in the blotchy mouse, in the absence of a defect in hepatic copper uptake. We suggest that defective copper transport from hepatocyte to bile represents the hepatic expression of the mottled mutation and speculate that a similar defect occurs in human KHS. These conclusions are consistent with the hypothesis that the basic defect in mottled mutants and in KHS affects cellular copper transport or the intracellular delivery of copper to cellular transport systems.

ISSN:0031-3998    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Carnitine palmitoyltransferase deficiency realizes two distinct clinical forms. We previously showed and confirmed in the present work that CPTII (identified as the carnitine palmitoyltransferase activity assayable in detergent conditions) is decreased in the muscular form whereas it is unaffected and CPTI is decreased in the hepatic form. The antibody previously prepared against human liver mitochondrial CPTII recognizes the same enzyme in muscle, liver, and fibroblasts. Immunoprecipitation experiments were performed in fibroblasts from patients with the muscular and hepatic forms of the defect. As compared with controls, cell lines from two patients with the hepatic form of the defect did not exhibit any qualitative nor quantitative abnormality of cross-reacting material, whereas cell lines from two patients with the muscular form of the defect exhibited a decreased amount of cross-reacting material. These data suggest that CPTII deficiency could result from a decreased production of protein. The amount of cross-reacting material in the two sets of patients only correlates with CPTII activity, which is decreased in the muscular presentation and unaffected in the hepatic form. These results strengthen the hypothesis of distinct proteins supporting CPTI and CPTII activities.

ISSN:0031-3998    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

3-Phenylpropionic acid is an end-product of the bacterial degradation of unabsorbed phenylalanine in the intestinal lumen. As CoA ester, this metabolite has been considered to be a specific substrate for medium chain acyl-CoA dehydrogenase (MCAD). Its glycine-conjugate, 3-phenylpropionylglycine, has now been established as a pathognomonic marker in urine from patients affected with MCAD deficiency. However, no systematic studies to evaluate the reactivity of 3-phenylpropionyl-CoA with other known acyl-CoA dehydrogenases have so far been carried out to establish the specificity of this substrate for MCAD. We studied the in vitro reactivity of 3-phenylpropionyl- CoA with five rat and human liver acyl-CoA dehydrogenases using purified preparations. We demonstrated that MCAD effectively dehydrogenated 3-phenylpropionyl- CoA, and that no other acyl-CoA dehydrogenase exhibited any significant activity with this substrate. In the steady state condition, the Km of 3-phenylpropionyl-CoA for human MCAD was 50 mM. Gas chromatography/mass spectrometry analysis of the assay mixture identified transcinnamoyl- CoA as the product of the reaction. Furthermore, we showed by determination of the reaction products using gas chromatography/mass spectrometry selected ion monitoring that, in absence of the primary electron acceptor, 3-phenylpropionyl-CoA was slowly but significantly dehydrogenated by MCAD under aerobic conditions. These data suggest that MCAD may oxidize 3-phenylpropionyl- CoA in vivo using an alternative electron acceptor, to produce frans-cinnamoyl-CoA. This mechanism provides an explanation for the normal 3-phenylpropionylglycine excretion observed in urine from patients affected with glutaric aciduria type II and ethylmalonic/adipic aciduria.

ISSN:0031-3998    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The ability of peripheral blood mononuclear cells (PBMC) from newborn infants, gestational age 24-42 wk, to produce interferon-α (IFN-α) on the first day after birth was studiedin vitro. Human amnion cells (WISH) coated with herpes simplex virus type I and fixed by glutaraldehyde were used as IFN-α inducers. Individual IFN-α producing cells (IPC) among PBMC were determined by an immunoplaque assay. The frequency of IPC was low in all premature (≤36 wk) infants (median 0.3 IPC/104PBMC, range 0.0–2.6), and significantly higher (median 2.0 IPC/10437 wk). The frequencies were lower in both groups of infants than in adults (7.3 IPC/104PBMC, range 2.0–23.7). When a conditioned medium from cultures of herpes simplex virus type I-stimulated PBMC from adults was added to the IFN induction cultures, the frequencies of IPC increased in PBMC from both preterm and term infants, and in the latter group did not differ significantly from adult levels. The median production of IFN-α per IPC was 1.1 U (range 0.0–2.8) in premature infants, 1.0 U (range 0.0–8.8) in term infants and 3.2 U (range 1.5–8.0) in adults. When concentrations of PBMC in the cultures were decreased, a decline of IPC frequencies occurred. This decline was more marked and started at higher PBMC concentrations in infants than in adults, and was prevented by addition of conditioned medium from herpes simplex virus type I-stimulated cultures of PBMC from adults. The results suggest that PBMC of preterm infants on the first day after birth are deficient both with respect to the proportion of actual IPC and to accessory mechanisms necessary for a normal IFN-α response. In contrast, IPC frequencies in term infants approach levels of adults, but accessory functions may still be deficient.

ISSN:0031-3998    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Various studies have demonstrated pronounced systemic IgG response to Pseudomonas aeruginosa (PA) infection in cystic fibrosis (CF). However, antibody response to serotype-specific lipopolysaccharides (LPS) has never been studied. ELISA for detection of IgG antibodies to LPS of nine PA-serotypes and to toxin A were performed with serum of 78 CF patients. Anti-LPS profiles of antibodies were confirmed by SDS-PAGE and immunoblotting techniques. The most frequent PA-serotypes found were immunotypes (IT) IT-1 and IT-2, and Habs-3 and Habs-4. Ten patients without PA colonization showed no detectable antibody titers. In patients with chronic PA colonization (n=46), these antibody titers were significantly (p<0.005) higher than in patients with intermittent PA colonization (n=22). Mean serum antibody titers to LPS of PA IT-1, IT-2, Habs-3, and Habs-4 correlated with duration of PA colonization and with disease severity. Subclass analysis of anti-LPS antibodies revealed elevated levels for all four IgG subclasses and for IgA1. The IgG antibodies to LPS of PA proved to be protective in a murine burn wound sepsis model. We conclude that anti-LPS antibodies to specific PA serotypes in serum may be a sensitive measure of severity and prognosis of CF. Patients with CF show adequate functional immune response to LPS of PA, and it is possible that vaccination against PA before colonization could induce protective immunity.

ISSN:0031-3998    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

We studied the major determinants of opsonophagocytosis against Streptococcus pneumoniae serotypes 14 and 19 in paired cord/maternal sera from 27 healthy term and 24 preterm infants in an attempt to gain more insight in the susceptibility of newborns to pneumococcal infection. For both pneumococcal serotypes studied, opsonic activity in neonatal sera varied greatly, but was moderately to profoundly deficient when compared to paired maternal sera, both in preterm (34.5 and 34.9% of the activity in maternal serum, for serotypes 14 and 19, respectively, p<0.001 for both) and in term serum (43.5 and 52.7% of the activity in maternal serum, for serotypes 14 and 19, respectively, p<0.001 for both). The opsonic deficiency in preterm sera could be ascribed to a diminished level of the major opsonins for pneumococci, i.e. complement factor C3 deposited on the bacterial surface (69.5 and 66.2% of C3 deposition in maternal serum on serotypes 14 and 19, respectively, p<0.01 for both) and specific anticapsular IgG antibodies (48.5 and 14.1% of maternal levels for serotypes 14 and 19, respectively, p<0.001 for both). However, the opsonic defect in serum from term infants could not be explained in a similar way, because C3 deposition and specific anticapsular IgG levels were equal to the values found in the paired maternal sera. Therefore, we conclude that the opsonic defect in newborn serum for pneumococci cannot be solely explained by a deficiency in the major opsonins for these bacteria. A dysfunction in these opsonins seems to be a more likely explanation for the observed opsonic defect in the neonate.

ISSN:0031-3998    

出版商:OVID    

年代:1990

数据来源: OVID