Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The estradiol (E2) to estriol (E3) ratio during human pregnancy depends on fetal liver hydroxylation of fetal adrenal dehydroepiandrosterone sulfate (DHEAS) and conversion by the trophoblast of DHEAS and 16 alpha-hydroxy-DHEAS (16 OH-DHEAS) to estrone (E1), estradiol (E2), and estriol (E3), respectively. It is not known whether the conversion of DHEAS into E1 and E2 influence the conversion of 16OH-DHEAS into E3 and vice versa. To examine this question, we studied these interactions in human choriocarcinoma JEG-3 cells. In serum-free medium (Dulbecco's Modified Eagle's Medium), JEG-3 cells secreted hCG [27 +/- 3 (+/- SEM) ng/mg cellular protein X 24 h] and progesterone (22 +/- 2.5), but neither C-19 nor C-18 steroids. The addition of DHEAS resulted in secretion of E1 and E2; at a concentration of 500 ng DHEAS/ml, the secretion of E1 (1 +/- 0.16) and E2 (11 +/- 3.1) was maximal, while E3 remained undetectable. The addition of 1000 ng 16 OH-DHEAS/ml resulted in maximum E3 secretion (13 +/- 1.8), while E1 and E2 remained undetectable. The addition of increasing concentrations of DHEAS to cultures exposed to 1000 ng 16OH-DHEAS/ml caused a decrease in E3 secretion and increased secretion of E1 and E2. Conversely, addition of increasing concentrations of 16OH-DHEAS in cultures exposed to 500 ng DHEAS/ml resulted in inhibition of E1 and E2 secretion and increased E3 secretion. A concentration of 16OH-DHEAS that inhibited the conversion of DHEAS into E1 and E2 neither altered the intracellular to extracellular steroid ratios (approximately 0.1) nor reduced the secretion of DHEA, androstenedione, and testosterone. The inhibitory effect of 16OH-DHEAS was minimal at low DHEAS concentrations (favoring the secretion of E1 and E2) and was greatly enhanced at concentrations of DHEAS that induced maximum E1 and E2 secretions. The results indicate that in trophoblastic cells, the metabolism of DHEAS can modulate E3 secretion, and the metabolism of 16OH-DHEAS can modulate the secretion of E1 and E2; and this regulatory mechanism appears to take place at the level of the aromatase system.
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PMID:Competitive studies with dehydroepiandrosterone sulfate and 16 alpha-hydroxydehydroepiandrosterone sulfate in cultured human choriocarcinoma JEG-3 cells: effect on estrone, 17 beta-estradiol, and estriol secretion. 294 57

Rat reticulocytes contain a cytosol activator protein (RCAP) that augments catecholamine-sensitive adenylate cyclase activity in reticulocyte membranes. A highly purified preparation of RCAP, obtained by Sephacryl S-200 chromatography, was used to elucidate further its mechanism of action. The specific activity of the S-200 fraction to augment isoproterenol responsiveness was increased approximately 1,100-fold over the starting material, from 1.2 to 1,300 nmol cAMP formed per mg RCAP. The mol wt of RCAP is approximately 20,000. The effect of RCAP to enhance isoproterenol responsiveness was apparent within 20 sec, virtually abolishing the normal lag time of hormone-activated adenylate cyclase. In addition to its effects on catecholamine-responsive adenylate cyclase, RCAP significantly increased basal [21 +/- 3 (+/- SEM) to 41 +/- 4 pmol/mg protein X 30 min; P less than 0.02], guanyl-5'-yl-imidodiphosphate-associated (3173 +/- 213 to 4339 +/- 365 pmol/mg X 30 min; P less than 0.03), and fluoride-associated (5152 +/- 64 to 5807 +/- 58 pmol/mg X 30 min; P less than 0.05) adenylate cyclase activities. RCAP also altered the characteristics of agonist binding to the beta-adrenergic receptor of reticulocyte membranes, causing an increase in the apparent IC50 for isoproterenol from 0.7 +/- 0.2 to 7.9 +/- 1.6 microM (P less than 0.001). Similar to its effects on reticulocytes, RCAP enhanced isoproterenol- and prostaglandin E2-sensitive adenylate cyclase activity in the wild-type S49 lymphoma cell and shifted the binding isotherm for isoproterenol rightward. In cyc-, the mutant that lacks the stimulatory guanine nucleotide-binding protein (Ns) and in UNC, the mutant in which receptors are uncoupled from N, RCAP was ineffective. Moreover, RCAP decreased agonist affinity for the beta-adrenergic receptor in wild-type S49 cells, but not in cyc- or UNC cells. These observations suggest that RCAP requires a functional Ns unit for its effects on hormone-sensitive adenylate cyclase activity.
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PMID:Cytosol activator protein from rat reticulocytes requires the stimulatory guanine nucleotide-binding protein for its actions on adenylate cyclase. 298 18

Estrogen 16 alpha-hydroxylase activity was measured in microsomes prepared from fetal tissues of first and second trimester human abortuses using [16 alpha-3H]estrone sulfate as substrate and NADPH as cofactor. Estrogen 16 alpha-hydroxylase activity was demonstrable in 13 of 14 fetal tissues examined in this study, viz. liver, adrenal fetal zone, adrenal neocortex, lung, kidney, intestine, heart, brain, skin, testis, spleen, pancreas, and stomach, and was either negligible or absent in placental tissue. The highest specific activity of the microsomal enzyme [pico-moles of product(s) formed per mg protein/h] was found in liver (mean +/- SEM, 338 +/- 62), and the next highest was found in the fetal zone of the adrenal cortex (70 +/- 20). The specific activities of estrogen 16 alpha-hydroxylase in adrenal neocortex, brain, skin, and testis were similar (25-53 pmol/mg protein X h) as were those in lung, kidney, intestine, heart, spleen and stomach (23-36 pmol/mg protein X h). The specific activity of the enzyme in the pancreas was 12 pmol/mg protein X h; the lowest specific activity, however, was in placental microsomes (0.2 +/- 0.1 pmol/mg protein X h).
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PMID:Estrogen 16 alpha-hydroxylase activity in human fetal tissues. 372 30

Choline acetyltransferase (ChAT) activity was estimated in brain cortex capillaries isolated from 3-, 12-, 18-, and 24-month-old rats. Maximum enzymatic activity was found at 12 months (55 +/- 0.3 pmol X mg-1 protein X min-1; mean +/- SEM) and then it decreased to reach a minimum at 24 months (34 +/- 3.1 pmol X mg-1 protein X min-1). A less marked decrease of enzymatic activity was also found in cortex homogenate and in a synaptosomal fraction obtained from the same groups of rats. Loss of ChAT of brain capillaries with aging could be related to a general phenomenon of cortical cholinergic deficit in that condition.
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PMID:Decrease of choline acetyltransferase activity of rat cortex capillaries with aging. 400 78

A model for whole body glycine nitrogen flux based on the compartmental analysis of plasma [15N] glycine decay curves is described and used for the measurements of (1) total body glycine nitrogen flux and the components of this flux in three healthy young adults and (2) total body protein synthesis based on the conversion of 15N to excretory products, ie, the sum of urinary [15N] urea and 15NH3 and the amount of labeled urea remaining in the body at five hours following administration of [15N] glycine. The mean glycine nitrogen flux was 3.93 +/- 0.42 mg N X kg-1 X h-1 (SEM). The major components of this flux are de novo synthesis of glycine, which accounts for 18% to 27%, and release from protein breakdown, which accounts for 62% to 73%. The outward pathways of glycine from the total body free glycine pool are conversion to other amino acids and oxidation to excretory end products (30% to 42%) and incorporation into protein, which accounts for 45% to 61% of glycine N loss from the metabolic pool. The mean rate of total body protein synthesis as determined by compartmental analysis was 3.56 g protein X kg-1 X day-1. The results that were obtained for protein synthesis and whole body glycine kinetics accord well with previous studies in normal adults, using the stochastic model.
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PMID:A model for determination of total body protein synthesis based upon compartmental analysis of the plasma [15N] glycine decay curve. 686 54

Exhaled nitric oxide (NO) concentration is a noninvasive measure of airway inflammation and is increased in asthma. Inhaled glucocorticoids decrease exhaled NO concentration, but the relative contributions of alveolar and bronchial levels to the decrease in exhaled NO concentration are unknown. Alveolar NO concentration and bronchial NO flux can be separately approximated by measuring exhaled NO at several exhalation flow rates. The effect of steroid treatment on alveolar and bronchial NO output in asthma was studied. Alveolar NO concentration and bronchial NO flux were assessed in 16 patients with asthma before and during treatment with inhaled fluticasone for 8 weeks and in 16 healthy controls. Before the treatment, asthmatics had increased bronchial NO flux (mean+/-SEM: 3.6+/-0.4 versus 0.7+/-0.1 nL x s(-1), p<0.001) but normal alveolar NO concentration (1.2+/-0.5 versus 1.0+/-0.2 parts per billion (ppb), p>0.05) compared with controls. Inhaled fluticasone decreased bronchial NO flux from 3.6+/-0.4 to 0.7+/-0.1 nL x s(-1) (p<0.01) but had no effect on alveolar NO concentration (before: 1.2+/-0.5; after: 1.2+/-0.1 ppb, p>0.05). The forced expiratory volume in one second improved, whereas asthma symptom score and serum levels of eosinophil cationic protein and eosinophil protein X decreased during the treatment. In conclusion, inhaled fluticasone decreases bronchial but not alveolar nitric oxide output simultaneously with clinical improvement in patients with asthma.
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PMID:Inhaled fluticasone decreases bronchial but not alveolar nitric oxide output in asthma. 1171 67

Biochemical evaluation of inflammation may be a useful adjunct to measures of pulmonary function and symptoms in children with asthma. However, little data have been provided to validate the markers in children. The aim of the present study was to assess circadian variations in serum eosinophil cationic protein (ECP), and serum and urine eosinophil protein X (EPX) in children. Five girls and two boys aged 10-14 years were studied. The first sample of urine consisted of urine collected from 24.00 hours the night before until 08.00 hours on the morning of the day of investigation. Thereafter urine was collected at 4-h intervals until 24.00 hours and in another 8-h interval from 24.00 to 08.00 hours. Blood samples for assessment of serum ECP and serum EPX were collected every 2 h during the 24 h. Statistically significant circadian variations in serum ECP (F=3.2, p=0.002), serum EPX (F=3.1, p=0.002) and in urine EPX/creatinine (F=5.4, p=0.003) were detected. The concentrations were higher during the night compared to daytime. Peak levels of serum ECP (mean [+/- SEM]) were found at 06.00 hours (16.3 [5.3] micro g/l), trough levels at 08.00 hours (3.9 [0.7] micro g/l) (p=0.01). Peak levels of serum EPX were seen at 06.00 (43.7 [9.5] micro g/l) with trough levels at 12.00 hours (22.0 [3.5] micro g/l) (p=0.01). Peak levels of urine EPX/creatinine occurred in urine collected from 24.00 to 08.00 hours (90.0 [27.7] micro g/mmol), trough levels in the 16.00-20.00 hours sample (29.7 [8.9] micro g/mmol) (p=0.02). Serum ECP, serum EPX and urine EPX exhibit a circadian variation in children with nocturnal and early morning peak levels. To avoid confounding influence from circadian variations in ECP and EPX in clinical studies blood or urine should be sampled at consistent times.
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PMID:Circadian variations in serum eosinophil cationic protein, and serum and urine eosinophil protein X. 1267 59