ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Group B streptococci (GBS) localizing in the lungs of infant piglets is killed in part by an oxygen radical-dependent mechanism (Bowdy BD, Marple SL, Pauly TH, Coonrod JD, Gillespie MN: Am Rev Respir Dis 141:648–653, 1990). The source of bactericidal oxygen radicals is unknown, but cyclooxygenation of arachidonic acid, an initial event in prostanoid synthesis, is accompanied by substantial oxygen radical generation. Because blockade of prostaglandin H synthase (cyclooxygenase) with indomethacin prevents GBS-induced pulmonary hypertension, we reasoned that the salutary effect of indomethacin might be associated with a reduction in the efficacy of bactericidal activity directed against GBS. To address this possibility, the distribution and viability of111In-labeled GBS (108colony forming units/kg/min i.v. for 15 min) were assessed in lungs and livers of control piglets, piglets treated with indomethacin (1 mg/kg), and piglets treated with OKY-046 (10 mg/kg), an inhibitor of thromboxane synthase that also forestalls GBS-induced pulmonary hypertension. Relative to control animals, indomethacin treatment increased pulmonary GBS uptake with no change in bacterial distribution into the liver. OKY-046 failed to influence pulmonary bacterial uptake but promoted a substantial increase in GBS depositing in the liver. In contrast to its effects on pulmonary bacterial deposition, indomethacin failed to increase lung bacterial viability relative to control animals. Indomethacin also was without effect on hepatic bacterial viability. OKY-046 failed to influence pulmonary bacterial viability but markedly augmented hepatic GBS viability to the extent that significant bacterial proliferation occurred. Both indomethacin and OKY-046 abolished GBS-induced pulmonary hypertension by preventing the increase in pulmonary arterial pressure and decrease in cardiac output. Viewed collectively, these observations suggest that oxygen radicals derived from cyclooxygenation of arachidonic acid in GBS-treated piglets do not contribute to microbicidal activity directed against the organism. (Pediatr Res31: 14–17, 1992)

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Several deficiencies in antibacterial defense have been described in neonates. Among those best characterized are delayed maturation of B cells into antibody producing cells, deficient T-cell maturation, and delayed cycling of hematopoietic progenitor cells after an infectious challenge. No unifying theory has been forwarded, however, to explain the concomitance of these three developmental deficiencies. IL-6, a cytokine produced primarily by monocytes and macrophages in response to stimulation by IL-1, is involved in the regulation of these three processes. Thus, we postulated that defective production of IL-6 could be a mechanism underlying these immune deficiencies of neonates. Indeed, we observed that at peak production, cells of five term neonates produced only one half as much IL-6 (14 120 ± 2590 pg IL-6/108monocytes) as those of five adults (28 940 ± 1680 pg,p< 0.001). Peak production was lower still by monocytes of six preterm neonates (7190 ± 1400 pg,p< 0.001versusterm). Production of IL-6 protein was inhibited by actinomycin D and the IL-6 mRNA content of monocytes from neonates, as assessed by competitive polymerase chain reaction, was less than that of adult monocytes. We speculate that defective IL-6 transcription might underlie some of the defects in immune regulation observed in neonates. (Pediatr Res31:18–21, 1992)

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Perinatal transmission of human immuno-deficiency virus (HIV) from infected mothers to their children occurs at rates reported as 20–50%. The role of breast feeding in perinatal transmission of viral infections has not been well established. We studied 34 milk and colostral samples obtained from HIV-seropositive and HIV-sero-negative women to determine if they contained anti-HIV activity. We found that all the samples contained a factor that inhibited the binding of HIV epitope-specific MAb to recombinant CD4 receptor molecules. The titers of inhibitory activity ranged from 1:200 to 1:10 000 and did not differ between HIV-seropositive and HIV-seronegative mothers. This milk factor also inhibited the binding of gp120 to CD4. Neither human sera nor bovine milk exhibited appreciable inhibitory activity. Fractionation of human milk indicated that the inhibitory activity was confined to the macromolecular fraction; little activity was found in isolated milk lipids or oligosaccharides. Chromatographic procedures indicated that the active macromolecule has an isoelectric point of 9.3–9.6. The active material did not bind to concanavalin A; however, the activity was partially destroyed by chemical and enzymatic treatments that removed sulfated residues. The active material may thus be a sulfated protein, glycoprotein, mucin, or glycosaminoglycan that inhibits the binding of CD4 to HIV envelope glycoproteins. The role of this factor in the natural history of HIV infection in infants and children should be the subject of additional investigations. (Pediatr Res31: 22–28, 1992)

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

We previously demonstrated that certain biologic activities in human milk were partially blocked by antibodies directed against human tumor necrosis factor-α (TNF-α). In this study, immunochemical methods were used to verify the presence of TNF-α in human milk obtained during the first few days of lactation. Gel filtration revealed the presence of TNF-α by RIA in molecular weight fractions between 80 and 195 kD. TNF-α could not be detected consistently by conventional Western blotting or cytotoxic assays. Although immunoreactive bands were detected by a Western blot-125I protein A technique in TNF-α-positive fractions from gel filtration, those bands proved to be nonspecific. TNF-α in milk was reliably quantified by the competitive RIA. Those studies revealed that the concentrations of TNF-α in milk were 620 ± 183 pg/mL. Although RNA to TNF-α was detected in milk leukocytes by Northern blotting, little TNF-α was found in those cells before or after stimulation with N-formyl-l-methionyl-l-leucyl-l-phenylalanine or 4β-phorbol-12β-myristate-13α-acetate. The origin of this cytokine in human milk remains unclear. Nevertheless, this study suggests that TNF-α is present in early human milk in sufficient quantities to exert possible biologic effects upon the mammary gland of the mother or the immune system of the infant. (Pediatr Res31: 79–33, 1992)

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is a common autosomal recessive disorder of mitochondrial fatty acid oxidation characterized by episodes of hypoketotic hypoglycemia usually beginning in the first 2 y of life. We previously showed, in pulse labeling experiments, that the biosynthesis and immediate posttranslational processing of MCAD are normal in fibro-blasts from patients with MCAD deficiency. Most patients studied to date are homozygous for a point mutation (A985-G) that results in the substitution of glutamate for lysine at residue 304 of the mature MCAD subunit. We performed immunoblot analysis of fibroblast MCAD from a total of 34 patients with MCAD deficiency, including 31 homozygous for the A985-G mutation, using a rabbit anti-rat MCAD antibody that cross-reacted specifically with human MCAD, but not with the related enzymes, short-chain and long-chain acyl-CoA dehydrogenases. All patients with the A985-G mutation lacked detectable MCAD. Pulse-chase labeling of MCAD-deficient fibroblasts with35S-methionine demonstrated that this variant MCAD was unstable compared to controls. Taken together, these data suggest that this mutation affects the stability of MCAD protein within the mitochondrial matrix. (Pediatr Res31: 34–38, 1992)

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The activity of medium-chain acyl-CoA de-hydrogenase (MCAD) with octanoyl-CoA as a substrate was measured in human lymphocytes by a gas chromatographic technique. Phenazine methosulfate was used as the primary electron acceptor. After the addition of crotonase and subsequent hydrolysis, the reaction product 3-hydroxyoctanoic acid was quantitated by capillary gas-liquid chromatography of the trimethylsilyl derivatives. Control subjects had MCAD activities of 3.46 ± 0.18 nmol/mg protein/min (n= 15). Five patients were investigated while receiving no therapy at all; MCAD activity ranged from 0.08 to 0.23 in four of them and was 0.65 in the fifth one. Subsequent to the long-term administration of 50–150 mg/d of riboflavin to MCAD-deficient patients (n= 11), these activities increased to an average of 0.41 in 10 patients and 2.22 in one. The activities in 15 obligate heterozygotes were 1.91 ± 0.41 nmol/mg protein/min, thus enabling a clear distinction from controls. Neither heterozygotes nor a control responded to riboflavin. The method was also applicable to postmortem liver tissue. One patient, who had died suddenly and unexpectedly at the age of 19 mo, was correctly diagnosed as MCAD-deficient, whereas five additional children who died of the sudden infant death syndrome showed normal activities. (Pediatr Res31: 39–41, 1992)

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Immunoblot analyses with bovine fumaryl-acetoacetase antibodies have been performed in fibroblast extracts from 28 patients with hereditary tyrosinemia of various clinical phenotypes, in one healthy individual homozygous for a “pseudodeficiency” gene for fumarylac-etoacetase, and in three tyrosinemia families in which one or both parents are compound heterozygotes for the tyrosinemia and pseudodeficiency genes. Liver extracts from two chronic patients were also investigated. None of the patients with the acute type of tyrosinemia had detectable immunoreactive protein in fibroblast extracts. Only two of seven patients with typical chronic tyrosinemia had definite immunoreactivity in fibroblasts. In liver tissue, one of the patients had cross-reactive material and the other had no immunoreactivity. Four of 13 patients with intermediate clinical findings showed immunoreactivity in fibroblasts. There was no relationship between severity of symptoms and amount of cross-reactive material in this group. The psendodeficiency gene product gave almost no detectable immunoreactivity in fibroblasts. The results indicate that chronic tyrosinemia may be due to at least two protein variants, and immunobloting does not classify tyrosinemia patients according to clinical findings. (Pediatr Res31: 43–46, 1992)

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Our objective was to determine the quantitative changes of individual triacylglyercol (TG) species in liver and carcass during early postnatal growth. Pregnant rats were killed at d 21 of pregnancy, and neonatal rats were killed at d 3 or 9 after birth. Quantitative changes in fatty acids and TG species of fetal/neonatal liver and carcass were determined using capillary gas liquid chromatography. At postnatal d 3 or 9 compared with fetal d 21, total carcass TG increased 11− to 12-fold, with nonessential fatty acids increasing 8− to 9-fold, n-6 essential fatty acids (EFA) increasing 34− to 44-fold, and n-3 EFA increasing 19− to 29-fold, respectively. Total neonatal liver TG increased 13-fold from fetal d 21 to postnatal d 3, with a 6-fold increase in non-EFA, a 34-fold increase in total n-6 EFA and a 65-fold increase in total n-3 EFA. At postnatal d 3 compared with fetal d 21, larger molecular weight liver TG classes (C56-C64) increased 68-fold, followed by lower molecular weight TG classes C40-C48 (19-fold) with only a 6-fold increase in C50-C54. In liver, highly unsaturated TG classes (C56-C64) accounted for 49% of total TG at postnatal d 3 and consisted mainly of arachidonic, docosahexaenoic, and linoleic acids accompanied by palmitic and oleic acids. During early postnatal development, TG species containing one, two, or even three 20–22 EFA may be structurally important themselves or serve as direct substrates for synthesis of phospholipids. The unique accumulation of C54-C64 TG species, especially in liver, indicates that highly unsaturated TG are a quantitatively important EFA pool during early life. (Pediatr Res31: 47–51, 1992)

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Kinetics of glycerol metabolism and triglyceride/fatty acid cycling were quantified in 12 healthy, normal, appropriate-for-gestational-age (AGA) infants, eight small-for-gestational-age (SGA) infants, and five infants of insulin-dependent diabetic mothers (IDM) at less than 48 h of age. Stable isotope-labeled [2-13C]glycerol and [6,6-2H2]glucose in combination with indirect respiratory calorimetry were used. The tracers were used as constant rate infusion and steady state isotopic enrichment of glucose, glycerol, and bicarbonate was measured by mass spectrometric methods. After a 7− to 9-h fast, the plasma glucose, glycerol, and FFA concentrations were similar in the AGA and IDM groups. In the SGA group, the plasma glucose concentration was significantly lower than that in the AGA group throughout the study, but plasma FFA and glycerol concentrations were not different from those in the AGA infants. Plasma betahydroxybutyrate concentration was significantly elevated in the AGA group compared with IDM and SGA infants (AGA 0.59 ± 0.39, SGA 0.35 ± 0.09, IDM 0.33 ± 0.21 mmol/L; mean ± SD). The rate of appearance of glycerol was significantly elevated (p< 0.05) in SGA infants (AGA 9.47 ± 2.11, IDM 9.55 ± 2.14, SGA 12.15 ± 3.87 μmol/kg·min). Between 80 and 90% of glycerol turnover was converted to glucose, accounting for 20% of glucose turnover with no significant difference in the three groups. Approximately 35% of glycerol carbon was recovered in the bicarbonate (CO2) pool. Less than 5% of CO2carbon was derived from glycerol. Estimation of triglyceride-fatty acid cycle revealed that the triglyceride energy mobilized was increased in SGA infants. Only 22–24% of the triglyceride energy released was oxidized to CO2in the newborn infants; the majority (76–78%) was recycled back to the adipose tissue. These data show that lipolysis is active in the immediate neonatal period. The contribution of fat to oxidative metabolism is increased in SGA infants. The major metabolic fate of glycerol in the neonate is conversion to glucose, and glycerol is a minor contributor to oxidative metabolism. (Pediatr Res31: 52–58, 1992)

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID