摘要:

To test the hypothesis that acute hyperglycemia reduces changes in cell membrane structure and function during cerebral hypoxia in the newborn, brain cell membrane Na+, K+-ATPase activity and levels of membrane lipid peroxidation products were measured in four groups of anesthetized, ventilated newborn piglets: normoglycemia/normoxia (control, group 1,n= 12), hyperglycemia/normoxia (group 2,n= 6), untreated hypoxia (group 3,n= 10), and hyperglycemia/hypoxia (group 4,n= 7). Hyperglycemia (blood glucose concentration 20 mmol/L) was induced using the glucose clamp technique. The hyperglycemic glucose clamp was maintained for 90 min before onset of hypoxia and throughout the period of hypoxia. Cerebral tissue hypoxia was induced in groups 3 and 4 by reducing fraction of inspired oxygen for 60 min and was documented by a decrease in the ratio of phosphocreatine to inorganic phosphate as measured using31P-nuclear magnetic resonance spectroscopy. Blood glucose concentration during hypoxia in hyperglycemic hypoxic animals was 20.7 ± 1.2 mmol/L, compared with 10.3 ± 1.7 mmol/L in untreated hypoxic piglets (p< 0.05). Peak blood lactate concentrations were not significantly different between the two hypoxic groups (8.4 ± 2.8 mmol/Lversus7.8 ± 1.6 mmol/L). In cerebral cortical membranes prepared from the untreated animals, cerebral tissue hypoxia caused a 25% reduction in Na+,K+-ATPase activity compared with normoxic controls and an increase in conjugated dienes and fluorescent compounds, markers of lipid peroxidation. In contrast, Na+,K+-ATPase activity and levels of lipid peroxidation products in hyperglycemic hypoxic animals were not significantly different from the values in control normoxic animals. These data suggest that in the newborn piglet model acute hyperglycemia reduces hypoxia-induced brain cell membrane dysfunction.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The purpose of this study was to evaluate the visual development of preterm infants from 1 to 6 mo of age, using the pattern visual evoked potentials (VEP) in response to three check sizes: 60, 30, and 15 min of arc. Pattern VEP were recorded in 24 full-term and 24 preterm infants (26–36 wk of gestation). The results showed a rapid visual maturation between 1 and 3 mo, followed by a slower progression over the next 3 mo, in both groups. The implicit time of the P100 wave of the pattern VEP was also found to shorten with increasing check sizes. The maturation of pattern VEP in preterm infants was shown to be related to their gestational (or corrected) age rather than their postnatal age. The pattern VEP obtained in response to a 60-min check size in preterm infants aged between 1.5 and 2.5 mo (corrected age) showed a tendency for a faster maturation than those of full-term infants. Our results suggest that within the first 6 mo of age, pattern VEP response is useful to monitor visual development in full-term infants as well as in preterm infants using corrected age.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

To study the course of regional metabolite concentrations during early brain development, we measuredin vivometabolites [N-acetyl-aspartate (NAA), choline-containing compounds, andmyo-inositol (M-Ino)] in the precentral area of the cerebrum by short echo-time single volume proton magnetic resonance spectroscopy and comparedin vivoestablished spectroscopic data with classic chromatographic data (HPLC) on age-corresponding autopsy tissue in different regions of the brain. In autopsy tissue, regional (frontal lobe, precentral area, basal ganglia, thalamus) and age-dependent differences of the concentration of creatine, NAA, and M-Ino were determined.In vivomeasurement of NAA by proton magnetic resonance spectroscopy shows a significant increase of NAA by increasing postconceptional age. M-Ino shows a weak correlation and a nonsignificant decrease with increasing postconceptional age. Choline shows no age-dependent changes. Creatine concentrations measured by HPLC in different regions of the developing brain at autopsy showed an age-dependent increase that was identical for the left and right side and similar for the precentral area and frontal lobe and more pronounced for the basal ganglia and thalamus. Comparison of the results obtained by the two methods shows agreement for the age-dependent changes and the absolute concentration of M-Ino. NAA determined in autopsy tissue by HPLC is significantly lower than that measuredin vivoby proton magnetic resonance spectroscopy. A comparison of the concentrations measured by HPLC in frontal lobe, basal ganglia, and thalamus with the results obtained from the precentral area showed significant regional differences in all measured metabolites. These results define important age-dependent changes detected with both methods and further indicate limitations of both methods that have to be considered when presenting absolute concentration values.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Acute or subacute neurologic disorders can be observed in patients receiving high-dose methotrexate therapy for lymphoblastic leukemia or malignant tumor. Impairment of biopterin metabolism leading to decreased availability of monoamine neurotransmitters has been suggested to explain methotrexate neurotoxicity. To investigate such a mechanism, we have measured prospectively by HPLC the concentrations of total biopterin, homovanillic acid, and 5-hydroxyindolacetic acid in cerebrospinal fluid of 57 children with acute lymphoblastic leukemia. A sequential analysis of cerebrospinal fluid was performed for each patient: cerebrospinal fluid samples were obtained before therapy and after each of the four high-dose methotrexate infusions during the CNS prophylaxis phase. A significant increase of total biopterin concentrations in cerebrospinal fluid was observed after high-dose methotrexate therapy compared with the pretreatment values. No cumulative effect was noted. In contrast, no significant variation of the homovanillic acid and 5-hydroxyindolacetic acid levels was observed in cerebrospinal fluid. However, individual analysis revealed a transient decrease of homovanillic acid and 5-hydroxyindolacetic acid concentrations in cerebrospinal fluid of six children. The increase of total biopterin mimicking that observed in inherited dihydropteridine reductase deficiencies suggests that methotrexate inhibits the regenerating system of biopterin in the brain of patients undergoing high-dose methotrexate therapy.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Previous studies have suggested that,in vivo, activated T lymphocytes and neutrophils are important in immunity to nontypableHaemophilus influenzae.We now extend this work by showing that neutrophils pretreated with products of activated T lymphocytes or activated macrophages show significantly enhanced killing of nontypableH. influenzae.Lymphotoxin, a product of activated T lymphocytes, significantly enhanced the neutrophil-mediated killing of nontypableH. influenzae, and tumor necrosis factor, produced by activated T lymphocytes as well as macrophages stimulated by activated T lymphocytes, also significantly increased the bactericidal activity of neutrophils. These cytokine-induced effects were seen with short pretreatment times of neutrophils and were maximal by 30 min. The killing ofH. influenzaeby neutrophils required the presence of heat-labile opsonins. In the absence of these opsonins, both tumor necrosis factor and lymphotoxin were unable to promote the killing of the bacteria by neutrophils. Furthermore, the results showed that tumor necrosis factor-primed neutrophils displayed significantly increased expression of CR3 and CR4 that was associated with increased phagocytosis of complement-opsonized nontypableH. influenzae.These cytokines may play an important role in immunity toward nontypableH. influenzaeby stimulating neutrophil bactericidal activity.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

At the early stage of aseptic meningitis, there is a transient increase in neutrophil counts in the cerebrospinal fluid. Some factors in the cerebrospinal fluid might induce migration of neutrophils into the cerebrospinal fluid. Granulocyte colony-stimulating factor (G-CSF) plays an important role, not only as a hemopoietic factor but also as a regulating factor for a biologic defense system by neutrophils in the foci of infection. To analyze the role of G-CSF on accumulating neutrophils in the cerebrospinal fluid, we have measured G-CSF levels in the cerebrospinal fluid of children with aseptic meningitis, paying particular attention to the phasal transition. Within the first 2 d from the onset, G-CSF levels in the cerebrospinal fluid were 223 ± 97 ng/L, significantly higher than those of the patients without meningitis (p< 0.01). Beyond the second day after the onset, the G-CSF levels rapidly decreased to below the detectable level, even though the patients manifested meningeal signs and symptoms. There was a direct relationship between G-CSF levels and neutrophil counts in the cerebrospinal fluid (r= 0.763,p< 0.01). During the first 2 d after the onset, the G-CSF level in the cerebrospinal fluid in each case was remarkably higher than that in the serum. This finding suggests that the G-CSF in the cerebrospinal fluid was produced in the spinal cavity. From our results, the transient elevation of G-CSF levels might lead to the transient increase in neutrophil counts in the cerebrospinal fluid by recruiting them from the peripheral blood at the initial stage of aseptic meningitis.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Tumor necrosis factor-α (TNF) is a multifunctional protein hormone that contributes to host defense and perinatal immunologic development. Dysregulated TNF production, however, occurs during the pathogenesis of autoimmune diseases and may be inherent to their development. In animal models of autoimmunity, dysregulated TNF synthesis has resulted from mutations in TNF gene regulatory sequences, specifically those sequences involved in translational control of TNF gene expression. In this study, we have determined whether mutations in the TNF translational control sequences are present in pediatric patients with type I diabetes mellitus and connective tissue diseases. Blood samples were collected from 48 patients with connective tissue diseases, 32 patients with diabetes, and 29 controls. A 250-bp fragment of the translational control sequences present in the TNF 3'-untranslated region was amplified by the polymerase chain reaction, sequenced, and analyzed relative to the published TNF sequence. In this study, all patients and controls exhibited the normal sequence, with no insertions or deletions in the translational control motifs. We conclude that polymorphisms in the TNF 3'-untranslated region occur infrequently, if at all, in patients with diseases examined here.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Epidermal growth factor (EGF) in pharmacologic doses is able to induce growth and development in the fetus and the newborn. To investigate the opposite situation, the effects of insufficient amounts of EGF during development, we wanted to establish anin vivomodel with a state of EGF deficiency. This was attempted by induction of autoimmunity to EGF in rats. Twenty rats were immunized with EGF. Fifteen of these developed autoantibodies against EGF, which, as judged by Scatchard analysis, had a median apparent affinity constant of 14 X 109L/mol and a median concentration of binding sites of 20 X 10-9mol/L. The antibodies recognized purified EGF from the submandibular glands (6 kD) and from urine (45 kD) and further native EGF in saliva and urine. The cross-reactivity toward transforming growth factor-α was below 3%. Binding of EGF by antibodies inhibited its binding to the EGF-receptor by approximately 97%in vitro.Investigation ofin vivometabolism of antibody-bound125I-EGF confirmed these results, that is, the antibodies were able to inactivate EGF. The adult rats were unaffected by the induction and presence of autoantibodies, and the EGF-containing organs did not show any histologic signs of inflammation or tissue damage. Furthermore, as judged by immunohistochemistry, no major changes in the distribution and tissue concentration of EGF were seen in the adult rat. These results show that it is possible to induce homologous antibodies that can inhibit the binding of EGF to its receptor and further suggest that circulatory EGF is of no physiologic importance in the healthy, adult rat.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

We have used rats with epidermal growth factor (EGF) autoantibodies to study the role of EGF deficiency during perinatal development. The study was focused on organs known to contain EGF or its receptor. Compared with controls, the offspring of autoimmune rats had a higher perinatal mortality and a lower birth weight. The weight of the lungs was particularly low in the offspring of EGF-immunized rats, and morphologically the lungs from the surviving pups seemed atelectatic and had alveolar duct dilatation, which indicates mild respiratory distress syndrome. Judged from immunohistochemical studies, the amount of surfactant protein-A was decreased, suggesting a delayed lung maturation. The offspring of EGF-immunized rats had dry and wrinkled skin. The skin was thin and the hair follicles were immature. This suggests a role for EGF in the growth and development of the skin. The liver/body weight ratio was lower in pups from EGF-immunized rats. This difference was, however, not significant (p= 0.07), but flow cytometric analyses showed a significantly lower proportion of the liver cells from newborn EGF-deficient pups to be in S-phase and indicated that these cells were larger than liver cells from controls. To study possible alterations in EGF binding,125I-EGF was injected i.v. in newborn rats.125I-EGF bound in all the organs investigated. The binding is listed in decreasing order: liver, gut, skin, kidney, and lungs. In the pups from EGF-immunized rats, the lungs and the skin bound a significantly higher amount than the controls. This could represent an upregulation of the EGF receptor in response to the lack of EGF. Postnatally, the pups from EGF-immunized mothers grew faster and were on paar with controls within 1 wk. We found no differences concerning tooth eruption, ear opening, and eye opening. In extension of present knowledge concerning the tissue localization of EGF and its receptor and concerning the pharmacologic effects of EGF, our study demonstrates an effect of EGF deficiency. This supports a role for EGF in the epigenetic regulation of the development of the lungs, the skin, and the liver.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Myocardial energy metabolism was studied in newborn sheep to determine whether the metabolic responses to pacing-induced increases in heart rate were similar to those previously found during catecholamine stimulation. Open-chest newborn sheep, 3 to 9 d old (n= 11), underwent atrial pacing at a respiratory rate harmonic just above the intrinsic heart rate. Pacing rate was increased by 30 beats/min every 5 min until conduction block or a drop in systemic arterial pressure occurred. Phosphorous metabolites were monitored simultaneously (n= 7) using a31P magnetic resonance surface coil over the heart within a magnet operating at 4.7 tesla. Myocardial oxygen consumption was monitored via an extracorporeal shunt from the coronary sinus. Rate pressure product increased with heart rate and was found to relate to myocardial oxygen consumption (r= 0.75), which increased maximally by 47 ± 9% due to increases in coronary blood flow. Phosphocreatine/ATP ratio decreased significantly, and calculated ADP increased between baseline and peak performance but returned to near baseline levels during recovery at the initial pacing rate. These findings indicate that intracellular high-energy phosphate concentrations do change with alterations in myocardial oxygen consumption induced by cardiac pacing in the newborn. These changes are similar to those found during epinephrine infusion. Furthermore, the ATP hydrolysis products probably participate in myocardial respiratory regulation in the newbornin vivo.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID