Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029713 (immaturity)
4,335 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the role of receptors with high and low affinity for fMLF chemotaxic peptide in the generation of active oxygen species by umbilical cord blood granulocytes from newborns with normal neonatal period, born after normal or complicated gestation, in children with manifestations of bacterial infection born after complicated pregnancy, and in granulocytes of non-pregnant women with normal reproductive function. Granulocytes of children born after complicated pregnancy exhibited high reactivity in induction of respiratory burst in a wide range of fMLF concentrations. The presentation of receptors with high and low affinity on granulocytes during initiation of the respiratory burst differs in children born after complicated pregnancy and in healthy babies born after normal gestation. Presumably, the detected differences result from high expression of receptors with low affinity for fMLF and disorders or immaturity of mechanisms responsible for receptor inactivation.
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PMID:Evaluation of the Role of FMLF chemotaxic peptide receptors in umbilical cord blood granulocytes from newborns at risk of infectious inflammatory diseases. 1911 May 92

Many of the morbid conditions associated with extreme immaturity are potentiated by an excess of free radicals occurring in infants who developmentally have decreased levels of antioxidants. The optimal oxygen saturation values for the resuscitation, stabilization, and ongoing care of the very low birth weight infant remain largely undefined. We have reviewed the currently available evidence for clinical oxygen use in the newborn period. Until the results of further studies are available, a reasonable approach to resuscitation would include initial resuscitation with 30-40% oxygen for very preterm infants using targeted SpO2 values and blended oxygen during the first 10 min. For ongoing management of preterm infants, SpO2 targets of 85-93% seem to be most appropriate, with alarm limits set within 1 to 2% of these targets with intermittent audits to ensure compliance. There is no strong evidence to support the use of altered limits for the infant who develops early evidence of retinopathy of prematurity. Further prospective studies are required to evaluate the effects of varied oxygen targets on long-term outcome.
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PMID:Oxygen saturation monitoring for the preterm infant: the evidence basis for current practice. 1912 13

This review emphasizes the predictive ability, sensitivity and specificity of aquatic plant biomarkers as biomonitoring agents of exposure and effect. Biomarkers of exposure are those that provide functional measures of exposure that are characterized at a sub-organism level. Biomarkers of effect require causal linkages between the biomarker and effects, measured at higher levels of biological organization. With the exception of pathway specific metabolites, the biomarkers assessed in this review show variable sensitivity and predictive ability that is often confounded by variations in growth conditions, rendering them unsuitable as stand alone indicators of environmental stress. The use of gene expression for detecting pollution has been, and remains immature; this immaturity derives from inadequate knowledge on predictive ability, sensitivity and specificity. Moreover, the ability to the detect mode of action of unknown toxicants using gene expression is not as clear-cut as initially hypothesized. The principal patterns in gene expression is not as clear-cut as initially hypothesized. The principal patterns in gene expression are generally derived from stress induced genes, rather than on ones that respond to substances with known modes of action (Baerson et al. 2005). Future developments in multivariate statistics and chemometric methods that enhance pattern analyses in ways that could produce a "fingerprint", may improve methods for discovering modes of action of unknown toxicants. Pathway specific metabolites are unambiguous, sensitive, correlate well to growth effects, and are relatively unaffected by growth conditions. These traits make them excellent biomarkers under both field and laboratory conditions. Changes in metabolites precede visible growth effects; therefore, measuring changes in metabolite concentrations (Harring et al. 1998; Shaner et al. 2005). The metabolic phase I enzymes (primarily associated with P-450 activity) are non-specific biomarkers, and few studies relate them to growth parameters. P-450 activity both increases and decreases in response to chemical stress, often confounding interpretation of experimental results. Alternatively, phase II metabolic enzymes (e.g., glutathione S-transferases; GST's) appear to be sensitive biomarkers of exposure, and potentially effect. Some GST's are affected by growth factors, but others may only be induced by xenobiotics. Measuring xenobiotic-induced GST's, or their gene expression patterns, are good candidates for future biomarkers of the cumulative load of chemical stress, both in the laboratory and under field conditions. Phytochelatins respond to some but not all metal ions, and may therefore be used as biomarkers of exposure to identify the presence and bioavailability of ions to which they respond. However, more data on their specificity to, and interactions with growth factors, in more species are needed. The flavenoids are only represented by one heavy metal exposure study; therefore their use as biomarkers is currently difficult to judge. Stress proteins tend to be specific for toxicants that affect protein function. Growth factors are known to affect the level of stress proteins; hence, the use of stress proteins as biomarkers will be confined to experiments performed under controlled growth conditions, where they can be excellent indicators of proteotoxicity. Reactive oxygen species (ROS), ROS scavenging enzymes, changes in pigment content, photosynthesis and chlorophyll fluorescence are all affected by growth factors, particularly light and nutrient availability. Therefore, these biomarkers are best suited to investigate the mode of action of toxicants under controlled growth conditions. These biomarkers are sensitive to xenobiotic stressors that affect various processes in the photosynthetic apparatus, and can be used to diagnose which photosynthetic process or processes are primarily affected. Chlorophyll fluorescence is a non-destructive measure, and is thereby well suited for repeated measures of effect and recovery (Abbaspoor and Streibig 2005; Abbaspoor et al. 2006; Cedergreen et al. 2004). Bi-phasic responses (over time and with dose) are probably major sources of variation in sensitivity for many biomarkers. Metabolic enzymes, stress proteins, ROS and their corresponding scavenging enzymes increase in a time-frame and at doses in which plant cell damage is still repairable. However, when toxicity progresses to the point of cell damage, the concentration/activity of the biomarker either stabilizes or decreases. Examples of this response pattern are given in Lei et al. (2006); Pflugmacher et al. (2000b); Teisseire et al. (1998); and Teisseire and Guy (2000). Gene expression is also a time-dependent phenomenon varying several fold within a few hour. Therefore, bi-phasic response patterns make timing and dose-range, within which the biomarkers can be used as measures of both exposure and effect, extremely important. As a result, most biomarkers are best suited for situations in which the time and dose dependence of the biomarker, in the investigated species, are established. Notwithstanding the previously mentioned limitations, all assessed biomarkers provide valuable information on the physiological effects of specific stressors, and are valuable tools in the search for understanding xenobiotic modes of action. However, the future use of aquatic plant biomarkers will probably be confined to laboratory studies designed to assess toxicant modes of action, until further knowledge is gained regarding the time, dose and growth-factor dependence of biomarkers, in different species. No single biomarker is viable in gaining a comprehensive understanding of xenobiotic stress. Only through the concomitant measurement of a suite of appropriate biomarkers will our diagnostic capacity be enhanced and the field of ecotoxicology, as it relates to aquatic plants, advanced.
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PMID:Biomarkers in aquatic plants: selection and utility. 1925 39

Obstructive lung diseases remain as important complications of preterm birth, usually attributed to a combination of lung immaturity, oxygen therapy and ventilator support. This is particularly true for low birth weight infants with severe respiratory neonatal disease; however, preterm infants that did not initially demonstrate significant respiratory neonatal disease also have reduced lung function when examined later in life, suggesting that prematurity alone could generate a persistent obstructive disease. Recent data have shown a significant reduction in maximal expiratory flows in healthy premature infants compared with control infants and reference values, when tested in the first months of life. Reduced expiratory flows were associated with male sex, low gestational age, smoking exposure and increased weight gain. The mechanism for this has not been determined and could result from smaller airways, a decrease in pulmonary elastic recoil secondary to abnormal alveolarisation of the lung parenchyma, as well as more compliant airways.
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PMID:Effect of preterm birth on airway function and lung growth. 1965 91

Chronic lung disease of prematurity (CLD) is commonly considered to be a consequence of assisted ventilation. However, prior to the description in 1967 of bronchopulmonary dysplasia (BPD), following ventilator therapy for respiratory distress syndrome, Wilson-Mikity syndrome (WMS) had been described in very preterm infants on minimal oxygen supplementation. In the 1970s and 1980s, many infants treated with assisted ventilation required prolonged mechanical ventilation after developing radiographic features of coarse infiltrates, severe hyperinflation, and microcystic changes, associated with hypercarbemia and the need for increased inspired oxygen concentrations. Some infants died and showed evidence of pulmonary fibrosis, obstructive bronchiolitis, and dysplastic change. The role of supplemental oxygen, positive pressure ventilation, and the immaturity of the lung have long been considered important in the etiology of CLD/BPD. More recently, the role of inflammation (particularly antenatal exposure to cytokines) and individual susceptibility (genetic predisposition) have assumed greater etiologic importance. The historical setting into which corticosteroid treatment for BPD was introduced is also discussed. After the licensing of exogenous surfactant to treat RDS in the early 1990s and more widespread use of prenatal corticosteroids in the mid-1990s, severe BPD became an unusual event. Gradually, the diagnosis of CLD, still often referred to as BPD, was based on an oxygen requirement at 36 weeks postmenstrual age. However, it is not clear that this 'new BPD' is substantially different from WMS. It is difficult to make prognostications about long-term lung function of these infants based on oxygen 'requirement' at 36 weeks, since supplemental oxygen is frequently used unnecessarily.
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PMID:Chronic lung disease of prematurity: a short history. 1969 62

This chapter provides recommendations on pig islet product manufacturing and release testing to scientific and corporate programs interested in future clinical studies using xenogeneic porcine pancreatic islet cell products for the treatment of type 1 diabetes.To facilitate control of manufacturing as well as reproducibility and consistency of product lots, the manufacturing process, and the manufacturing facility must be in compliance with current Good Manufacturing Practices regulations. Data must be provided to demonstrate that islet products can be consistently prepared that would meet basic lot release requirements. To facilitate product safety: (i) materials used in the manufacturing process, including the pig pancreas, must be free of adventitious agents; (ii) islets must be manufactured using aseptic processing; and (iii) final product must undergo tests for sterility, mycoplasma (if cultured) and endotoxin. Safety specifications for pig islet product release include a negative Gram stain and an endotoxin content of <5.0 EU/kg recipient body weight. Product post-release assessments must include sterility cultures on the final product. Because results for sterility are available only retrospectively, a plan of action must be in place for patient notification and treatment in case the sterility culture results are positive for contamination. Product characterization information must address important aspects of lot release testing such as identity/purity (cell composition), quantity [islet equivalents (IE), cell number] and potency (insulin secretory capacity, oxygen consumption rate corrected for DNA or transplant bioassay in immunoincompetent diabetic mice). This information is also critical to demonstrate manufacturing control and product consistency across multiple islet preparations (lots). Providing islet products containing an islet mass sufficient to restore euglycemia in trial participants (>or=10 000 IE/kg) requires pooling of islets from multiple donor pancreata (two to four from adult donors and seven to 10 from neonatal donors). Demonstration of product consistency across products from individual pancreata would warrant release testing to be performed on a sample of the pooled product. As product development and clinical trials advance, the increasingly more detailed specifications of potency assays on adult porcine islet products are expected to be predictive of post-transplant glycemic control. The immaturity of fetal and neonatal porcine islet tissue precludes the use of in vitro insulin secretion as a potency test as part of lot release testing; another measure of potency appropriate to fetal and neonatal cells will need to be developed for product release testing and evaluation of aliquots of these products in mouse transplant bioassays should be performed to provide meaningful post-release information.
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PMID:The International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes--chapter 3: Pig islet product manufacturing and release testing. 1979 62

Intraventricular hemorrhage (IVH) is a major complication of prematurity. IVH typically initiates in the germinal matrix, which is a richly vascularized collection of neuronal-glial precursor cells in the developing brain. The etiology of IVH is multifactorial and is primarily attributed to the intrinsic fragility of the germinal matrix vasculature and the disturbance in the cerebral blood flow (CBF). Although this review broadly describes the pathogenesis of IVH, the main focus is on the recent development in molecular mechanisms that elucidates the fragility of the germinal matrix vasculature. The microvasculature of the germinal matrix is frail because of an abundance of angiogenic blood vessels that exhibit paucity of pericytes, immaturity of basal lamina, and deficiency of glial fibrillary acidic protein (GFAP) in the ensheathing astrocytes endfeet. High VEGF and angiopoietin-2 levels activate a rapid angiogenesis in the germinal matrix. The elevation of these growth factors may be ascribed to a relative hypoxia of the germinal matrix perhaps resulting from high metabolic activity and oxygen consumption of the neural progenitor cells. Hence, the rapid stabilization of the angiogenic vessels and the restoration of normal CBF on the first day of life are potential strategies to prevent IVH in premature infants.
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PMID:Intraventricular hemorrhage in premature infants: mechanism of disease. 1981 35

Prematurity apnea remains a major clinical problem that requires treatment choices which are sometimes difficult. Prematurity apnea occurs in most infants of gestational age at birth less than 33 weeks. It is a developmental disorder which usually reflects a "physiological" immaturity of respiratory control. However, neonatal diseases may be associated and play an additive role, resulting in an increased incidence of apnea. Careful screening should therefore be performed in order to make sure that no other factor than immaturity is involved in the occurrence of apnea. Short apnea (less than 10s, without hypoxemia and bradycardia), due to immaturity, are not clinically relevant. More prolonged apnea, that last for more than 15 or 20s, and / or apnea associated with bradycardia or oxygen desaturation, results in short-term disturbances of cerebral haemodynamics and oxygenation, which may negatively impact on neurodevelopmental outcome. Evaluating the immediate severity of apnea and the risks that apnea may affect long-term outcome remains a challenge. The choice of treatments is based on a few evidences. Caffeine citrate, which reduces the incidence of apnea, has been used for decades. However, a thorough evaluation of risks and benefits of this medication has been performed only recently. Caffeine citrate was found to be safe and resulted in unexpected benefits. In treated infants, compared with controls, indeed, a decreased incidence of the following complications was recorded: bronchopulmonary dysplasia at 36 weeks of conceptional age, patent ductus arteriosus, cerebral palsy at 18 months of age. Nasal CPAP can be used in association with caffeine citrate, when the latter is not effective enough.
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PMID:[Apnea of prematurity: what's new?]. 1994 73

Adult marine mammal muscles rely upon a suite of adaptations for sustained aerobic metabolism in the absence of freely available oxygen (O(2)). Although the importance of these adaptations for supporting aerobic diving patterns of adults is well understood, little is known about postnatal muscle development in young marine mammals. However, the typical pattern of vertebrate muscle development, and reduced tissue O(2) stores and diving ability of young marine mammals suggest that the physiological properties of harbor seal (Phoca vitulina) pup muscle will differ from those of adults. We examined myoglobin (Mb) concentration, and the activities of citrate synthase (CS), beta-hydroxyacyl coA dehydrogenase (HOAD), and lactate dehydrogenase (LDH) in muscle biopsies from harbor seal pups throughout the nursing period, and compared these biochemical parameters to those of adults. Pups had reduced O(2) carrying capacity ([Mb] 28-41% lower than adults) and reduced metabolically scaled catabolic enzyme activities (LDH/RMR 20-58% and CS/RMR 29-89% lower than adults), indicating that harbor seal pup muscles are biochemically immature at birth and weaning. This suggests that pup muscles do not have the ability to support either the aerobic or anaerobic performance of adult seals. This immaturity may contribute to the lower diving capacity and behavior in younger pups. In addition, the trends in myoglobin concentration and enzyme activity seen in this study appear to be developmental and/or exercise-driven responses that together work to produce the hypoxic endurance phenotype seen in adults, rather than allometric effects due to body size.
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PMID:Postnatal development of muscle biochemistry in nursing harbor seal (Phoca vitulina) pups: limitations to diving behavior? 2014 Jun 78

Liver injury causes vascular disorganization and local tissue hypoxia starting early in disease course. In this context, hypoxia acts not only as an aggravating factor of cell damage and inflammation, but also as an inhibitor of liver regeneration, a major stimulus of angiogenesis and fibrogenesis, and a promoter of liver carcinogenesis. Many of the effects of hypoxia are mediated by hypoxia-inducible factor-1alpha (HIF-1alpha), an oxygen-sensitive transcription factor. Compared to cells in the periportal area, intralobular hepatic stellate cells (HSCs) are more responsive to hypoxia and like other pericytes play a key role in angiogenesis through interactions with endothelial cells VIA platelet-derived growth factor (PGDF) and vascular endothelial growth factor (VEGF) signaling, at the leading edge of fibrotic septa. Although required for successful liver repair, angiogenesis in cirrhosis may be inefficient because of the immaturity and permeability of VEGF-induced neo-vessels, and thereby may fail to correct liver hypoxia. The multiple receptor tyrosine kinase inhibitors, acting on VEGF and PDGF receptors, initially designed for cancer treatment, show in addition to therapeutic efficacy in patients with hepatocellular carcinoma, beneficial effects on many aspects of the progression of liver diseases, including, fibrosis, inflammation and portal hypertension.
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PMID:Hypoxia: a link between fibrogenesis, angiogenesis, and carcinogenesis in liver disease. 2066 78


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