ISSN:0031-3998    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

In eight patients with Legg-Perthes disease, we assessed the etiologic roles of thrombophilia caused by protein C and protein S deficiency and hypofibrinolysis mediated by low levels of tissue plasminogen activator activity. We speculated that thrombosis or hypofibrinolysis were common causes of Legg-Perthes disease. Three of the eight patients had protein C deficiency; they came from kindreds with previously undiagnosed protein C deficiency. In one of these three kindreds there were six protein C-deficient family members (beyond the proband child), four of whom had thrombotic events as adults. One of the eight patients had protein S deficiency, as did his brother who had sustained mesenteric vein thrombosis at age 43. One of the eight patients who had normal proteins C, S, and antithrombin III had hypofibrinolysis, failing to elevate tissue plasminogen activator activity after 10 min of venous occlusion at 100 mm Hg. Plasminogen activator inhibitor, α2-antiplasmin, and fibrinogen values were normal in all eight patients. Beyond their Legg-Perthes disease, none of the eight patients had evidence for venous thrombosis. Of the eight patients, four had thrombophilia and one had hypofibrinolysis, disorders that we believe contributed to thrombotic venous occlusion of the femur with subsequent venous hypertension and bone death that characterize Legg-Perthes disease.

ISSN:0031-3998    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Previous studies demonstrated that, compared with adult serum, neonatal serum contained a diminished concentration of complement component C9 and that supplemental C9 enhanced the capacity of neonatal serum to kill an isolate ofEscherichia coli.Therefore, experiments were designed to determine the mechanisms by which supplemental C9 enhances the bactericidal capacity of neonatal serum and to determine whether supplemental C9 enhances the capacity of neonatal serum to kill several different pathogenic strains ofE. coli.A radiobinding assay and immunogold electron microscopy using a monoclonal anti-C9 antibody revealed that, compared with 40% adult serum, neonatal serum deposited a diminished quantity of C9 ontoE. coliO7w:K1:NM. Supplemental C9 (75 mg/L) significantly enhanced the quantity of C9 deposited by the neonatal serum. Treatment with 10 mM MgEGTA (a mixture of 100 mM MgCl2and 100 mM EGTA that blocks activation of the classic complement pathway but leaves the alternative pathway intact) abolished the capacity of neonatal serum to deposit C9 and to kill the bacteria. Supplemental C9 enhanced the capacity of neonatal serum to kill eight different blood isolates ofE. coli.Therefore, supplemental C9 enhanced the capacity of neonatal serum to killE. coliby increasing the total quantity of C9 deposited via activation of the classic complement pathway. Neonatal serum contained sufficient quantities of classic pathway components, other than C9, to deposit the supplemental C9 ontoE. coliand to enhance bacterial killing. The bactericidal activity of neonatal serum against multiple isolates of pathogenicE. coliwas increased after C9 supplementation. We speculate that C9 deficiency may be one of the defects in antibacterial host defense that predisposes neonates to the acquisition ofE. colisepsis.

ISSN:0031-3998    

出版商:OVID    

年代:1994

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Mononuclear phagocytes (MO) secrete tumor necrosis factor-α (TNF) in response to inflammatory stimuli, most notably the bacterial product lipopolysaccha-ride (LPS). Cross-linking of MO Fc receptors also induces TNF release. Immunoglobulin for i.v. use is currently being investigated for the treatment and prophylaxis of neonatal sepsis and for the treatment of various syndromes of autoimmune dysfunction in children and adults. We examined the invitroeffect of immunoglobulin-γ (IgG) on neonatal (cord blood) monocyte and adult MO TNF production. Kinetic studies were performed on MO incubated with IgG alone and on MO preincubated with IgG and stimulated with interferon-γ/LPS. Incubation of MO in IgG (1–25 g/L) for 2, 6, and 24 h did not stimulate TNF secretion or production. However, enhanced TNF secretion was detected in MO preincubated in IgG and subsequently stimulated with interferon-γ/LPS. TNF secretion by cord blood monocytes was increasingly enhanced by preincubation for 6 h with 1, 10, and 25 g/L IgG (2413.1 ± 1389.4,p< 0.05; 4070.4 ± 3069.2,p< 0.005; and 6383.7 ± 2982.2,p< 0.005versus1215 ± 575.9 ng/L, respectively, in cells preincubated in medium alone). Significant enhancement was also detected in cord blood monocytes preincubated in IgG for 2 h. TNF secretion by adult MO was similarly enhanced (6082.0 ± 1732.8,p< 0.05; 7158.8 ± 3938.2,p< 0.05; and 7302.7 ± 3451.4,p< 0.05versus3353.2 ± 2946.7 ng/L for 1, 10, and 25 g/L IgG, respectively,versuspreincubation in medium alone). In additional experiments performed with Fc, Fab, and F(ab‘)2fragments, only F(ab’)2fragments yielded positive results. Northern analyses revealed increased levels of mRNA for TNF only when 25 g/L IgG were used for preincubation. Preincubation in the lower concentrations of IgG did not result in increased accumulations of TNF mRNA. Thus, IgG acts primarily posttranscriptionally to enhance interferon-γ/ LPS-induced TNF releasein vitro.

ISSN:0031-3998    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Zinc is important for normal cell growth and differentiation, DNA synthesis, and gene expression. IGF-II is a fetal growth and differentiation factor whose regulation is largely unknown. To assess the effect of zinc (Zn) on fetal hepatocyte IGF-II expression and DNA synthesis, primary cultures of ovine fetal hepatocytes were studied in serum-free medium containing 1 μmol/L Zn or supplemented to 10 or 50 μmol/L Zn. Fetal hepatocyte DNA synthesis, Zn and protein content, IGF-II mRNA, and IGF binding protein production were measured. Zn concentration in medium increased slightly in unsupplemented dishes, from 1 to 1.5 μmol/L; however, Zn concentration declined by 4 and 8 μmol/L over 24 h in culture medium supplemented to contain either 10 or 50 μmol/L Zn (p< 0.05). Zn content of cell pellets increased 155 and 204% after 24 h in supplemented cultures compared with unsupplemented controls, demonstrating uptake of Zn by the liver cells. Media Zn supplementation to 10 and 50 μmol/L decreased3H-thymidine incorporation of cells in culture by 11 and 13%, respectively, compared with 1 μmol/L Zn (p= 0.001). Addition of Zn caused a progressive 2− to 3-fold decline in the nuclear labeling index of fetal hepatocytes, whereas the labeling index of nonhepatocytes increased almost 2-fold at 50 μmol/L compared with 1 μmol/L Zn. Associated with decreased hepatocyte DNA synthesis, IGF-II mRNA abundance declined by almost 30%. IGF binding protein content of conditioned medium did not change with added Zn. Cellular DNA and protein contents did not vary after 24 h in culture with either 1, 10, or 50 μmol/L Zn, suggesting that Zn was not toxic to the cells. We conclude that Zn selectively decreases fetal hepatocyte proliferation in primary culture, whereas nonparenchymal cell growth is not inhibited. Some of this response may be caused by decreased expression of IGF-II, an automne growth factor for fetal hepatocytes.

ISSN:0031-3998    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The relationships between spontaneous variations in serum 24-h osteocalcin (OC), carboxyterminal propeptide of type I procollagen (PICP), and aminoterminal propeptide of type III procollagen (PIIINP) concentrations and GH secretion, measured as GH response to provocative pharmacologic stimuli and spontaneous GH secretion during 24 h, were evaluated in prepubertal normal children and in GH-deficient and GH-secreting short normal children (SNC). All the subjects showed a circadian rhythm in smoothed 24-h OC and PICP mean data with higher nocturnal values in comparison with diurnal values. Conversely, serum PIIINP concentrations did not vary throughout the day. In children with classic GH deficiency and nonclassic GH deficiency, mean 24-h serum levels and smoothed 24-h mean data for OC, PICP, and PIIINP were significantly reduced (p< 0.001) with respect to age-matched controls. SNC showed mean 24-h OC concentrations similar (p= NS) to those we found in age-matched controls, but they had significantly lower (p< 0.001) diurnal 12-h mean data in comparison with controls. SNC also showed both 24-h PICP and PIIINP mean data and smoothed 24-h PICP and PIIINP mean data significantly lower (fromp< 0.02 top< 0.001) at all the time points of measurement in comparison with controls. Twenty-four-hour PICP and PIIINP mean data were positively related to spontaneous 24-h GH concentrations (r= 0.77,p< 0.005 andr= 0.69,p< 0.005, respectively) and growth velocity (r= 0.85,p< 0.005, andr= 0.70,p< 0.005, respectively), whereas 24-h OC mean data were not. Our study suggests that circadian serum PICP and PIIINP concentrations show GH dependency in children with classic GH deficiency and those with nonclassic GH deficiency, but this was less evident in SNC. Serum PICP and PIIINP concentrations may reflect somatic growth in children with short stature that is or is not related to GH deficiency.

ISSN:0031-3998    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

CNS therapy for childhood leukemia has adverse effects upon growth and cognition. The cause of these deficits is unknown. In a rat model, we determined which agent, or combination of agents, in CNS therapy affected growth. Young Sprague-Dawley rats were exposed to cranial irradiation (1000 cGy), methotrexate (2 or 4 mg/ kg, intraperitoneally), or prednisolone (18 or 36 mg/kg, intraperitoneally) alone or in two- or three-agent combinations. Matched control groups received appropriate sham radiation, intraperitoneal saline, or both. Body weight was recorded from 14 through 150 d of age. After the rats were killed at 150 d, body length was recorded and the head and left femur were removed to determine body and craniofacial proportions. Cranial irradiation alone, but not methotrexate or prednisolone alone, stunted growth permanently and altered craniofacial proportions. When these agents were combined, methotrexate and prednisolone modified the growth response to cranial irradiation. Methotrexate given before cranial irradiation prevented radiation stunting in males. This protection was lost when the dose of methotrexate was increased, when prednisolone was added to the combination, or when females were studied. The protection in males was effective against both growth and behavioral deficits. These results indicate that the physical and behavioral side effects of CNS therapy are better understood in the context of dose, sex, and interactions of the agents.

ISSN:0031-3998    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

We evaluated the utility of alkaline phosphatase (AP) histochemical staining for studying intraparenchymal vascular morphology in the brain of a 31-wk-gestation (1480 g) neonate who died of respiratory insufficiency after 23 h. In this baby, afferent cerebral vessels (arteries, arterioles, and capillaries) stained with AP, whereas efferent vessels (venules, veins) did not. The large periventricular channels in the germinal matrix were determined to be veins, according to AP staining criteria. Arterioles connected with these large periventricular veins after passing through 4− to 6-μm capillaries. Branchings and connections of the cerebral circulation were conventional;i.e.no arterial rete or arteriovenous shunts were found. With this method of differential vascular staining, bleeding in the germinal matrix was found to be perivenous only. No dilated capillaries or arterioles were seen. Smooth muscle was identified in extrastriatal medullary arteries. This preliminary investigation suggests that AP histochemical staining is an excellent method for studying brain vascular morphology and pathology of the very-low-birth-weight neonate.

ISSN:0031-3998    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Phosphorus magnetic resonance spectroscopy is a noninvasive method to investigate brain metabolismin vivo.ATP generally serves as an internal concentration standard for the quantification of the various phosphorus metabolites, because the ATP concentration in mammalian brains is assumed to be age independent. This presumption is based on observations made in the biochemical analysis of the developing rat brain. In the present study, metabolite concentrations were assessed with an external concentration standard. Each brain spectrum was quantified using a calibration spectrum that was acquired from a phantom after thein vivobrain measurement. Fully relaxed localized brain spectra were obtained from 16 neonates (2–28 d), 17 infants (6–20 mo), and 28 adults (22–58 y). The metabolite concentrations (in mmol/L) changed from neonates to adults: phosphomonoester from 4.5 to 3.5, inorganic phosphate from 0.6 to 1.0, phosphodiester from 3.2 to 11.7, phosphocreatine from 1.4 to 3.4, and ATP from 1.6 to 2.9. We conclude that 1) the ATP concentration in the human brain almost doubles between neonates and adults, and 2) ATP may not be used as an age-independent internal concentration standard.

ISSN:0031-3998    

出版商:OVID    

年代:1994

数据来源: OVID