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)

The process of functional adaptation after extensive small bowel resection is complex and imprecisely understood. In vivo electrophysiological measurements for monitoring the functional adaptive process after massive small bowel resection in Brown-Norway rats were evaluated. Rats underwent either a sham operation (SH) or a 90% small bowel resection (SB). Standard rat chow was fed in unlimited quantities. At three or 10 weeks after operation, jejunal and ileal transepithelial potential differences (PD, mV) were determined. Electrogenic ion transport in the villus was measured after glucose (sodium coupled active glucose absorption; PD-glu) and in the crypt, after theophylline infusion (theophylline stimulated chloride secretion; PD-theo). Biopsies were taken simultaneously. Each experimental group consisted of three to five animals. At three weeks the PD-theo and PD-glu in SB rats were significantly lower than in SH rats in both jejunal and ileal segments. At 10 weeks PD-theo and PD-glu were significantly diminished in the jejunal segment of the SB rats compared with the SH rats. The values of PD-theo and PD-glu in the ileal segments were, however, no longer different between the two groups. Three and 10 weeks after operation the length of the villi in the SB group was increased significantly compared with the SH controls. These results indicate that in the early phase of adaptation in vivo electrophysiological variables do not correlate with histological changes in the SB rats. This might be due to cell immaturity resulting from an increased rate of cell turnover or lack of intercellular tight junctions. This hypothesis is supported by a recovery of PD responses in the ileum 10 weeks after resection.
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PMID:The value of in vivo electrophysiological measurements for monitoring functional adaptation after massive small bowel resection in the rat. 850 63

Pre-eclampsia is a placental disorder, but until now, biochemical details of dysfunction have been lacking. During an analysis of the oligosaccharide content of syncytiotrophoblast microvesicles purified from the placental chorionic villi of 10 primigravid women with proteinuric pre-eclampsia, we found an excess of glycogen breakdown products. Further investigation revealed a 10-fold increase in glycogen content (223 +/- 117 micrograms glycogen/mg protein), when compared with controls matched for gestational age at delivery (23 +/- 18 micrograms glycogen/mg protein) (P < 0.01). This was confirmed by examination of electron micrographs of chorionic villous tissue stained for glycogen. The increase in glycogen content was associated with 16 times more glycogen synthase (1,323 +/- 1,013 relative to 83 +/- 96 pmol glucose/mg protein per min) (P < 0.001), and a threefold increase in glycogen phosphorylase activity (2,280 +/- 1,360 relative to 700 +/- 540 pmol glucose/mg protein per min; P < 0.05). Similar changes in glycogen metabolism were found in trophoblast microvesicles derived from hydatidiform moles. Glycogen accumulation in villous syncytiotrophoblast may be a metabolic marker of immaturity of this cell which is unable to divide. The implications of these findings with regard to the pathogenesis of pre-eclampsia are discussed.
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PMID:Pre-eclampsia is associated with an increase in trophoblast glycogen content and glycogen synthase activity, similar to that found in hydatidiform moles. 851 82

The cause of the poor secretion of insulin in response to glucose by the beta-cell in the fetal rat pancreas is thought to be immaturity of the metabolism of glucose. Glucokinase (GK), a key enzyme in glycolysis, is the glucose sensor that maintains glucose homeostasis in the adult beta-cell; its role in the fetal beta-cell has not been determined. The aim of this study was to examine whether GK was functional in phosphorylation of glucose in the fetal islet, and if so, to determine what factors regulated this activity. Similar Km values were found in both fetal and adult islets: 7.4 vs. 7.7 mmol/l. The maximal GK velocity (Vmax) of the fetal islet and the contribution of GK to total glucose phosphorylation were also not significantly different from their adult counterparts. Western blot analysis of protein extracts from fetal and adult islets confirmed the presence of GK at 52 kDa. To determine if glucose had any effect on the Vmax of GK, islets were cultured for 7 days in medium containing low (1.4 or 2.8 mmol/l), normal (5.6 mmol/l), or high (11.2 or 16.8 mmol/l) concentrations of glucose. The maximal GK velocity increased linearly with increasing concentrations of glucose (r = 0.93; P < 0.01). To determine whether it was possible to up- and down-regulate Vmax of GK, islets were cultured in either a low (1.4 mmol/l) or high (30 mmol/l) concentration of glucose for 7 days and then switched to the opposite concentration for a further 3 days. The Vmax of GK in the fetal islet was upregulated 3.8-fold when the glucose concentration was raised. Conversely, the Vmax was downregulated 3.6-fold when the glucose concentration was lowered. The same phenomenon was also observed in the adult islet. These data indicate that GK is the glucose sensor for the fetal rat islet, just as it is for the adult islet. Since glucose did not cause insulin secretion from the fetal islet, it was important to examine whether this substrate had any effect on its own metabolism. Glucose utilization was estimated, and its Vmax was found to increase linearly with increasing concentrations of glucose (r = 0.96; P < 0.01). We conclude that the inability of the fetal rat beta-cell to secrete insulin in response to glucose cannot be explained by immaturity of GK or the glycolytic pathway.
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PMID:Glucose regulates the maximal velocities of glucokinase and glucose utilization in the immature fetal rat pancreatic islet. 869 Jan 54

Although the various aspects of digestion in the newborn have been studied for decades, we still lack quantitative information about the contribution of individual enzymes to the overall process. The information to date indicates that in spite of immaturity of many of the classical digestive mechanisms of the adult, the infant uses a number of compensatory systems to achieve adequate digestion of nutrients (Fig. 1). Thus, whereas in the infant gastric proteolysis is probably extremely limited, intestinal protein digestion is adequate. Although starch supplements are better tolerated in breast-fed infants, because of the compensation provided by human milk amylase, the infant is able to digest lactose and short-chain glucose polymers with endogenous brush border enzymes. Fat digestion is markedly aided by gastric lipase and, in breast-fed infants, the bile salt-dependent lipase of human milk. Thus, in the infant, gastric lipolysis is quantitatively much more significant than in adults. The absorption of human milk whey proteins (and probably also cow milk proteins) is probably associated more with the highly glycosylated form of these proteins than with immaturity of neonatal digestive enzymes.
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PMID:Digestion in the newborn. 878 Sep 1

Glucokinase (GK) is the glucose sensor in the adult beta-cell, resulting in fuel for insulin synthesis and secretion. Defects in this enzyme in the beta-cell are responsible for the genetic disorder maturity-onset diabetes of the young, with the beta-cell being unable to secrete insulin appropriately when challenged with glucose. The human fetal beta-cell is also unable to secrete insulin when exposed to glucose, but whether GK is present and functional in this developing cell is unknown. To determine the expression of GK in human fetal pancreatic tissue, cytosolic protein was extracted from human fetal islet-like cell clusters (ICCs) at 17-19 weeks gestation and examined for protein content and enzyme activity. On Western blots, a single band corresponding to GK was seen at 52 kDa, and this was similar to that obtained from human adult islets. The maximal velocity (Vmax) of GK was less in fetal ICCs than that in adult islets (8.7 vs. 20.7 nmol/mg protein x h); similar K(m) values were found in both ICCs and islets. No attempt was made to determine which cells in an ICC contained GK. Glucose utilization was determined radiometrically; the Vmax of the high K(m) component was less in ICCs than in islets (31.3 pmol/ICC x h vs. 101.4 pmol/islet.h). Culture of ICCs for 3-7 days in medium containing 11.2 mmol/L glucose resulted in a 3.7-fold increase in the Vmax of GK and a 1.8-fold increase in glucose utilization. These enhanced activities of glucose phosphorylation and glycolysis, however, did not lead to the beta-cell being able to secrete insulin when exposed to glucose. In conclusion, glucokinase is present and functional in human fetal ICCs, but the inability of the human fetal beta-cell to secrete insulin in response to an acute glucose challenge is not due to immaturity of this enzyme.
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PMID:Expression of glucokinase in glucose-unresponsive human fetal pancreatic islet-like cell clusters. 906 11

Plasma lipoprotein composition in infants receiving fat-free parenteral nutrition reflects the endogenous synthesis and metabolism of lipids. We studied the composition of plasma lipoproteins in 49 appropriate for gestational age newborn infants after surgery who received only glucose and amino acid solutions for 5.4 +/- 0.3 days (M +/- SE). Of the infants studied, 31 were fullterm (gestational age 39.5 +/- 0.2 weeks) and 18 premature (34.3 +/- 0.7 weeks). Plasma lipid levels (total lipids, triglycerides, free cholesterol, sterol, esters, phospholipids) did not differ between term and premature infants, but triglycerides and cholesterol were markedly lower than in young, fasting adults. The contribution of triglycerides to lipoprotein lipids was strikingly low in chylomicrons (21% vs. 90% in young fasting adults) and VLDL (34 vs 60%) and the infants had a consistently lower cholesterol content of HDL (21 mg/dl vs. 45-50 mg/dl in adults) and LDL (43 mg/dl vs. 100 mg/dl). All infantile lipoproteins were enriched with phospholipids. These results are comparable to those reported for cord plasma. In premature babies, VLDL were markedly reduced and contained less triglycerides, free and esterified cholesterol than in term infants. In contrast, HDL were increased in preterm infants and carried more phospholipids. VLDL contributed to al lesser and HDL to a greater extent to plasma lipid transport in premature infants. We conclude that in premature infants hepatic synthesis of triglycerides and cholesterol and their secretion as VLDL is reduced, which may be caused by low substrate availability or an immaturity of the synthetic pathway. In premature infants, HDL appears to play a major role in transporting plasma lipids to peripheral tissues.
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PMID:Immaturity alters plasma lipoprotein composition of intravenously alimented newborn infants. 951 74

Several groups have reported a risk of fetal macrosomia in pregnancies with maternal glucose intolerance which is intermediate between gestational diabetes (GDM) and normal glucose tolerance. The present study was designed to determine whether these pregnancies are also at risk for fetal obesity, hyperinsulinism and placental villous immaturity. 325 women with risk factors for GDM underwent a 75 g OGTT interpreted according to the O'Sullivan criteria. All women who met the criteria for GDM were managed with diet therapy. Insulin therapy was added for women with a mean serum glucose value > 100 mg/dl on a 24 hour glucose profile. Patients not meeting the GDM criteria were managed without special intervention. Primary outcome variables were measures of neonatal weight and skinfold thickness, fetal and neonatal insulin and glucose concentration, and placental villous maturation. Outcome parameters were compared among three groups: pregnancies with normal OGTT (control, n = 95), 1 abnormal value in the OGTT (1 abnl, n = 76) and GDM (n = 154). The outcome of pregnancies with 1 abnormal value in the OGTT was different from those with normal OGTT. Regarding fetal growth, rates of LGA were approximately twice as high in groups with one abnormal value and GDM (21% and 24%) compared to women with normal OGTTs (11%: p < 0.05 vs GDM and p = 0.07 vs 1 abnormal value). The percent of infants with skinfold thickness > 90th percentile was also greater in the 1 abnormal value and GDM groups (31.1 and 31.6% respectively) compared to controls (19.2%; p < 0.05 for GDM vs control only). Regarding fetal hyperinsulinism, AFI concentrations were similar in control and GDM groups (3.1 +/- 0.4 and 3.4 +/- 0.8 microU/ml, respectively), but were higher in the group with one abnormal OGTT value (4.3 +/- 1.2 microU/ml, p < 0.05 vs controls). Cord blood insulin: glucose ratios were elevated in both the 1 abnormal value and GDM groups (0.22 +/- 0.05 and 0.20 +/- 0.02 microU/ml per mg/dl), compared to controls (0.12 +/- 0.01 microU/ml per mg/dl, p < 0.05 vs 1 abnormal value). Neonatal glycemia < 30 mg/dl was significantly more common in the one abnormal value than in the control group (49% vs 34% of infants) and intermediate in the GDM group (40%). Severe placental villous immaturity was more than twice as frequent in the 1 abnormal value group compared to controls (24% vs 9%, p < 0.05) and the most frequent in the GDM group (33%; p < 0.001 vs controls). Pregnancies with glucose intolerance below the thresholds for diagnosis of GDM have an increased risk for fetal obesity, hyperinsulinism, postpartum hypoglycemia and placental immaturity. These findings indicate the continuum of risk for fetal morbidity associated with increasing maternal glucose intolerance in pregnancy.
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PMID:Hyperinsulinism, neonatal obesity and placental immaturity in infants born to women with one abnormal glucose tolerance test value. 959 64

So far, gestational diabetes treated with tolbutamide has never been associated with severe hypoglycaemia in the newborn when the mother's diabetes was well controlled. We report a case of a premature neonate, gestational age 34 weeks, with severe and long-standing hypoglycaemia from birth. The mother had well-controlled gestational diabetes, treated with tolbutamide from the 24th week of gestation until delivery. The neonate had inappropriately high levels of serum proinsulin, insulin and C-peptide relative to blood glucose concentrations. From day 19 after birth, the levels were normalized. Serum tolbutamide was 140.6 micromol/l (38 microg/ml) at 3 h after birth. Zero-order kinetics were seen during the first 90 postnatal hours. The half-life of serum tolbutamide decreased from 46 to 6 h. It is suggested that tolbutamide, when given to the mother until delivery, may cause severe and prolonged hyperinsulinaemic hypoglycaemia in premature neonates. The initially prolonged tolbutamide half-lives and zero-order kinetics suggest immaturity of hepatic elimination during the first 2 days of postnatal life.
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PMID:Prolonged elimination of tolbutamide in a premature newborn with hyperinsulinaemic hypoglycaemia. 967 39

In immature female rats (21 days), a restricted diet (50% of the daily normal intake for 25 days) interrupts sexual development, leaving animals in a state of sexual immaturity. Food restriction does not affect the use of glycogen in uteri isolated and increases 14CO2 production from U14C-glucose in relation to animals receiving normal feeding that reach sexual maturity. Indomethacin and acetylsalicylic acid stop the increase of glucose metabolism produced by underfeeding, without affecting the uteri of rats receiving normal feeding. The addition of PGE2 and PGF2alpha changes the inhibitory effect of indomethacin. Nordihydroguaiaretic acid produces the opposite effect, increasing glucose metabolism only in uteri isolated from immature animals. These results show that immature animals have a higher glucose metabolism if compared to mature rats. The restricted diet, which slows down sexual maturity, keeps this parameter high due to the influence of some eicosanoids.
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PMID:Effect of a restricted diet on the metabolism of glucose in uteri isolated from immature rats: influence of indomethacin and nordihydroguaiaretic acid. 984 89

To characterize differential behavior and the relationship between maternal blood glucose levels and behavior in fetuses of diabetic (n = 10) and nondiabetic (n = 20) women at 33 and 36 weeks gestational age (GA), spontaneous changes in fetal heart rate (FHR), body and breathing movements, and vibroacoustic stimulus elicited (3 stimulus/3 no-stimulus control trials) FHR changes and body movements were compared. Measures of maternal blood glucose levels were obtained immediately following testing; measures varied within normal range. Spontaneous behaviors showed no differences between groups and no relationship to maternal blood glucose levels. Sensory stimulation elicited similar average peak FHR accelerations (M = 17. 1/20.0 BPM) and average movement scores (2.0/2.6) across groups. In the diabetic group at 33 weeks GA, the nature of the FHR change over time, showed more varied patterns of response, a shorter latency to peak acceleration, was less organized, and less mature; as average maternal blood glucose levels increased, elicited body movements decreased. These findings suggest immaturity and differential functional development of sensory-motor response systems in fetuses of diabetic mothers.
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PMID:Fetal behavior in diabetic and nondiabetic pregnant women: An exploratory study. 1039 98


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