摘要:

We have identified two unrelated girls with chronic neutropenia [absolute neutrophil counts (ANC) 10–870 and 10–940/μL in patients 1 and 2, respectively] and severe defect in superoxide anion generation by granulocytes. Formyl-methionyl-leucyl-phenylalanine-induced superoxide release was 1.2 ± 0.9 and 1.9 ± 1.9% (mean ± SEM,n= 3) of normal controls‘, mean value in patients 1 and 2, respectively. However, granulocytes from both patients released a normal amount of superoxide upon stimulation with phorbol myristate acetate. Patient 2 exhibited characteristic features of Duane syndrome, a rare disorder of eye movement. Treatment of the patients with recombinant granulocyte colony-stimulating factor led to significant clinical improvements and reduction of infectious complications and to increases in the ANC, to 400–2100/μL in patient 1 and to 500–3000/μL in patient 2. Treatment with 5 μg/kg/d resulted in increased intracellular killing of opsonizedStaphylococcus aureusby granulocytes and an enhancement of superoxide release upon stimulation with formyl-methionyl-leucyl-phenylalanine in both patients up to 11.1 ± 6.0 and 13.5 ± 7.0% (mean ± SEM,n= 5) of normal controls’, mean value in patient 1 and patient 2, respectively. These data suggested that recombinant human granulocyte colony-stimulating factor treatment enhanced resistance to bacterial infection by stimulation of superoxide generation and increasing the bactericidal capacity of peripheral blood granulocytes.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Infants vertically infected with human immunodeficiency virus type 1 (HIV-1) often manifest profoundly deficient growth with failure to thrive. The pathologic mechanisms that produce growth failure associated with pediatric HIV infection are not clear. Transgenic mice homozygous for agag/poldeletion mutant of the infectious pro virus pNL4–3 have been found to manifest a similar growth failure pattern. To explore the influence of HIV-1 on fetal growth and maternal-fetal interactions, we examined intrauterine growth of transgenic and nontransgenic mice and evaluated the consequence of embryo transfer into normal and heterozygous transgenic mothers. Mice homozygous for the HIV transgene had normal intrauterine and birth weights but uniformly displayed severe growth retardation postnatally. Transgene expression was prominent in transgenic fetuses and their placentas and in uteri of transgenic mothers, as determined by Northern analysis. Although embryo transfer did not affect intrauterine growth, the pregnancy rate in transgenic mothers was markedly lower than in nontransgenic controls. In both fetal and neonatal tissues, transgene expression was significantly greater in homozygous animals when compared with heterozygotes, but the difference was magnified postnatally. These results suggest that HIV gene expression affected both mother and neonate. In the mother, expression of the HIV-1 transgene reduced postfertilization pregnancy rate. Once the animal was pregnant, however, the effects of transgene expression on the homozygous fetus were overcomein utero, possibly by the contribution of maternal factors or by inhibition of HIV-1 gene expression by a fetal or maternal factor(s). In the neonate, HIV-1 transgene expression increased dramatically in homozygotes and was associated with profound growth failure. Thus, the expression of HIV-1 and its consequences are complex and dependent on important maternal-fetal interactions.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Expression of IL-2, interferon-γ, and IL-3 mRNA and proteins was investigated in peripheral blood mononuclear cells from cord blood after activation with phytohemagglutinin, CD2, or CD3 MAb. The results showed that interferon-γ and IL-3 expression was decreased in cord peripheral blood mononuclear cells when compared with expression observed in adult peripheral blood mononuclear cells, irrespective of the stimulation used. In addition, in newborn cells a defect in IL-2 secretion and mRNA expression was observed in response to CD2 or CD3 MAb but not in response to phytohemagglutinin-mediated activation. We further analyzed the modulation of nonlymphokine genes under the same protocol of stimulations. The results indicate that in newborn cells, despite a reduced lymphokine expression observed after CD2 or CD3 MAb activation, the up-regulation of the T-cell receptor, CD8, and p56lckwas similar to that found in adult cells, as was also found after phytohemagglutinin activation of both types of cells. These data are in favor of a deficient T-cell responsiveness to CD2 or CD3 MAb in newborn cells. This impairment of the T-cell response appears to selectively affect lymphokine gene expression because the modulation of other genes also implicated in T cell activation is not altered.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Among coagulase-negative staphylococci,Staphylococcus epidermidisis the species most commonly implicated in catheter-related infections. Whether some staphylococcal organisms are inherently more virulent than others, or whether their ability to infect relates more to the sheer numbers of organisms at the catheter site, remains unclear. We therefore compared eight S.epidermidisisolates and two other coagulase-negative staphylococci using a murine model that allowed us to quantify catheter colonization and abscess formation in the same animal. The organisms were isolated from different clinically relevant settings and were classified according to their slime phenotype. The ability to evoke abscesses or colonize catheters in half of the animals (ID50) was assessed. ID50inoculum titers (log10data ± SD) ranged widely, from 8.5 ± 0.3 to 10.2 ± 0.2 for abscess formation (p< 0.005) and from 7.5 ± 0.5 to 10.3 ± 1.0 for catheter colonization (p< 0.005). ID50values by statistical criteria suggested variability among organisms in the ability to induce abscess formation. High slime production correlated with both parameters, but not with the clinical source of the isolate. Our findings demonstrate impressive heterogeneity in the ability of a representative group ofS. epidermidisisolates to colonize catheters and to evoke abscess formation and implicate slime productivity as a major virulence factor. The murine model used permitted simultaneous analysis of multiple factors involved in pathogenesis and should be useful in establishing the basis ofS. epidermidispathogenicity.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Escherichia coli RDEC-1 (serotype O15:H-) is a rabbit enteropathogen in whichin vivoenteroadherence is both site specific and age related. To determine whether these differences could be related to mucins, we evaluated inhibition of binding of AF/R1 piliated RDEC-1 by mucins isolated from various segments of intestine of rabbits at different ages. Mucin was purified from intestinal crude mucus by cesium chloride serial ultracentrifugation. RDEC-1 was grown to promote the expression of hydrophobic mannose-resistant AF/R1 pili. Quantitation ofin vitrobacterial binding was determined using a crystal violet colorimetric assay. In postweanling rabbits, inhibition of RDEC-1 binding by purified mucin derived from ileal segments (45.1 ± 2.6%, mean ± SEM) and proximal colonic segments (46.0 ± 5.5%) was less than purified mucins derived from jejunal segments (70.0 ± 2.0%) and distal colonic segments (71.0 ± 3.7%,p< 0.05) of the intestinal tract. In all age groups, mucins derived from jejunal segments inhibited RDEC-1 binding to a greater level than mucins derived from ileal segments. In addition, inhibition of binding by mucin derived from proximal small intestine of postweanling rabbits (70.0 ± 2.0%) was greater than that of weanling rabbits (55.2 ± 3.5%,p< 0.05) with suckling rabbit inhibition (62.1 ± 3.5%) between these two levels. We conclude that mucin inhibition of RDEC-1 adhesion is both age and region related and therefore may contribute to both age-related and site localization of bacterial infections of the intestinal tract.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Different nonsteroidal antiinflammatory drugs (NSAID), especially ibuprofen, are being considered as an alternative to indomethacin for use in the newborn and as antipyretics for infants. However, some of these NSAID have been shown to cause visual complications. We therefore studied the effects of different NSAID indomethacin 19.6 μ-mol/kg (7 mg/kg), diclofenac 15.7 μmol/kg (5 mg/kg), ibuprofen 48 and 194 μmol/kg (10 and 40 mg/kg), naproxen 79 μ,mol/kg (20 mg/kg), and flurbipro-fen 41 μmol/kg (10 mg/kg) on photopic and scotopic electroretinograms (ERG) and retinal prostaglandin E2, prostaglandin F2α, and 6-keto-prostaglandin F1α levels in piglets 1–5 d old. All NSAID decreased retinal prostaglandin levels, but their effects on the ERG were not identical. Indomethacin and diclofenac did not alter the ERG. In contrast, the propionic acid derivatives ibuprofen (the two doses used), naproxen, and flurbiprofen affected the amplitude as well as the implicit time of the ERG under photopic and scotopic conditions. These changes are suggestive of generalized alterations in the function of rods and cones. Prior inhibition of prostaglandin synthesis by indomethacin did not modify the effects of ibuprofen on the ERG. These findings thus show a dissociation between the effects of NSAID on the ERG and prostaglandin synthesis. Because ERG changes are associated with visual alterations, these effects of propionic acid derivatives should be taken into account before considering their use in infants.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

We sought to determine whether elevated circulating growth hormone (GH) concentrations in uremic prepubertal children are due to an increase in GH secretory activity by the pituitary gland or a decrease in the metabolic clearance of GH consequent to reduced GFR. Deconvolution analysis was applied to the nighttime plasma GH profiles of1) 11 children with preterminal chronic renal failure,2) 12 children with end-stage renal disease (ESRD), and3) a control group of matched children with idiopathic short stature (n= 12). Mean (± SEM) half-life of endogenous GH in children with ESRD (27.5 ± 2.7 min) and preterminal chronic renal failure (23.1 ±2.1 min) was significantly higher than in controls (14.8 ± 1.6 min;p< 0.001). GH half-life correlated inversely with GFR (r= −0.65,p< 0.001). The number of GH secretory bursts/10 h in ESRD (8.1 ± 0.4) was amplified compared with preterminal chronic renal failure (6.4 ± 0.5) and with controls (5.9 ± 0.4;p< 0.005). GH production rate varied over a broad range in the three groups: It was highest in ESRD (202 ± 56.6 mg/L/10 h; range 36–683), mainly as a result of an increased number of GH secretory bursts, and not statistically different in preterminal chronic renal failure (66.2 ± 11.4 mg/L/10 h; range 25–168) and in controls (129 ± 27.7 mg/L/10 h; range 39–392). Increased GH half-life, in concert with an increased GH production in some individuals with ESRD, leads to a 2.5-fold increase in the mean plasma GH concentration in ESRD compared with the two other groups (p< 0.005). However, total immunoreactive plasma IGF-I levels were indistinguishable between groups. This disruption of the normal relationship between circulating GH and total plasma IGF-I levels in ESRD suggests a relative insensitivity to the action of GH in uremia, at least in those target organs (e.g.liver) that contribute predominantly to circulating IGF-I levels.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Quantitation of the body's fat and lean masses is an important component of nutritional assessment. Such measurements, however, are difficult to conduct routinely in infants due to the numerous limitations of traditional methods. The application of total body electrical conductivity measurements for quantitating fat-free mass (FFM) overcomes many of these limitations. The instruments required to perform these measurements in pediatric patients (HP-2) have recently become commercially available, but their measurement performance has not been evaluated. In these studies, we compared the precision, day-to-day variability, and magnetic field profile of three HP-2 instruments. We also derived a new calibration equation that relates the FFM to the total body electrical conductivity measurement in piglets, and compared it with an equation (provided currently by the manufacturer) derived on a prototype instrument. The performance of the instruments was generally similar, although a significant difference in the magnetic field of one instrument was identified. The coefficient of variation of inanimate phantom measurements varied from ±0.2 to ±0.5%, and the day-to-day variability was generally similar. Such measurement error is significant (±0.035 to ±0.078 kg FFM) for small subjects. The new calibration equation was similar to the original equation; therefore, all the data were pooled to generate a new equation that is linear at least to 10 kg. Thus, the HP-2 total body electrical conductivity instruments, which can be safely and easily used to measure FFM and fat in infants through 1 y of age, proved to be reliable and precise, and results obtained from different instruments can be confidently compared.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Chromogranin A (CGA), a large acidic 48-kD protein, co-stored and coreleased by exocytosis with catecholamines, has been shown to be a precursor of peptides that exert feedback regulatory control on catecholamine secretion. In plasma, CGA levels increase in response to a large-amplitude physical stimulation in adult subjects and may be related to catecholamine levels. Any akin information is not yet available when the sympathoadrenal system is highly actived during birth. This activation is strongly related to parturition circumstances such as the mode of delivery. The aim of our study was to determine CGA plasma levels in infants delivered vaginally or by elective cesarean section and to investigate the possible correlation between CGA and catecholamine concentrations. Plasma levels of catecholamines (norepinephrine and epinephrine) and CGA were assessed by HPLC with electrochemical detection and immu-noenzymology, respectively. CGA and norepinephrine concentrations were significantly higher (p< 0.0002 andp< 0.02) in infants vaginally born than in the group delivered by elective cesarean section. A significant relationship (p< 0.04) was found between CGA and norepinephrine levels. However, for epinephrine, no significant difference was found between both groups. These results demonstrate the fetus' ability to corelease CGA and norepinephrine massively in response to stress of birth.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Plasma growth hormone-binding protein (GH-BP) activity and the levels of IGF-I and its binding proteins (IGFBP) were studied in eight girls with Turner's syndrome before and during recombinant-hGH (r-hGH) administration. Growth hormone and GH-BP activity were assayed at baseline and hourly, over a 12-h period, after an intramuscular bolus of 0.09 mg/kg of the hormone. After 7 d, each patient received r-hGH at 0.33 mg/kg/weekly s.c. every day at nighttime; plasma growth hormone-binding protein activity, blood IGF-I, and IGFBP were evaluated before and on d 7, 30, 180, and 360. Baseline reference values were obtained from 10 bone age-matched healthy girls. Basal GH-BP activity, IGF-I, and IGFBP levels were similar in patients and controls. Four h after the intramuscular injection, GH-BP activity maximally increased and returned to baseline 6–7 h later; during long-term r-hGH administration GH-BP activity peaked at +180 d but declined to pretreatment at +360 d. IGF-I, IGFBP-3, and IGFBP-4 increased under r-hGH and, in contrast to GH-BP activity, remained high throughout the study. In conclusion, in girls with Turner's syndrome, GH-BP activity, IGF-I, IGFBP-3, and IGFBP-4 are induced by r-hGH. However, the increase of IGF-I and IGFBP-3 does not require an increased level of the cellular growth hormone receptors, as suggested by the unchanged +360 d values of plasma GH-BP activity compared with baseline. The absence of an association among any of the biochemical parameters studied and the growth of the patients taking r-hGH suggests that a peripheral defect may affect their growth.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID