Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
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The purpose of the present study was to examine stimulation of gastrin release and the synthesis of gastrin directly by measurement of incorporation of [(3)H]tryptophan into gastrin in rat antral mucosal explants maintained in organ culture. Gastrin synthesis and secretion were assessed simultaneously at intervals over the 24-h duration of explant culture. Antral mucosal explants from fed female Wistar rats (4-5 wk, 100-150 g) were cultured at 37 degrees C (95% O(2)/5% CO(2)) in medium containing 70% Trowell-T8 and 10% NCTC-135 without unlabeled tryptophan, 10% dialyzed fetal calf serum and [(3)H]tryptophan (100 muCi/ml). Antral tissue was harvested at regular intervals during 24-h culture periods. Incorporation of [(3)H]tryptophan into immunoreactive gastrin was determined by techniques utilizing double-antibody immunoprecipitation. Antral tissue protein synthesis was assessed by measurements of incorporation of [(3)H]tryptophan into tissue protein of cultured antral explants. In paired experiments, gastrin synthesis and secretion in the presence of dibutyryl cAMP (DBCAMP) were compared to those observed under control conditions. Gastrin and protein specific activity progressively increased with time. Gastrin specific activity at 30 min increased from 3.3+/-0.5 (SEM) to 55.2+/-10.6 fmol [(3)H]tryptophan/pmol gastrin (or from 1.57+/-0.48 to 26.28+/-5.05 pmol [(3)H]tryptophan/mug gastrin) at 24 h: specific activity of antral tissue protein at 30 min increased from 33.6+/-8.4 to 1,660+/-236 fmol [(3)H]tryptophan/mug protein at 16 h. Culturing of explants for 4 h in the presence of cycloheximide (100 mug/ml) inhibited both gastrin synthesis and protein synthesis by greater than 90 and 95%, respectively. DBCAMP (10 mM) significantly increased both the synthesis and secretion of antral gastrin when compared with control cultured explants. Results of these experiments provide direct demonstration of gastrin synthesis by rat antral mucosal explants in organ culture, indicate that both gastrin and total antral protein synthesis are inhibited by cycloheximide, and demonstrate DBCAMP-induced stimulation of both gastrin synthesis and secretion, suggesting the potentially important role of cyclic AMP in gastrin cell function.
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PMID:Stimulation of gastrin secretion and synthesis in antral organ culture. 19 22

Reversion to tryptophan independence induced by 365-nm and 254-nm radiation was studied in Escherichia coli WP2s (B/r trp uvrA). Under aerobic conditions, the mutant frequency responses was of the fluence-square or "two-hit" type at both 365 and 254 nm when revertants were assayed on minimal agar supplemented with 2% nutrient broth (SEM plates). In contrast, when mutants were assayed on minimal agar supplemented with tryptophan only, the revertant yield was reduced to very low values at 365 nm, whereas values substantially greater than with SEM plates were obtained at 254 nm. Premutational lesions induced by both 365-nm and 254-nm radiation were photoreactivated more than 10-fold when assayed on SEM plates, implicating pyrimidine dimers as premutational lesions at both wavelengths. The strong photoreactivation of 365-nm-induced mutagenesis contrasted strikingly with the complete absence of photoreactivation of 365-nm-induced lethality in this strain.
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PMID:Near-UV mutagenesis: photoreactivation of 365-nm-induced mutational lesions in Escherichia coli WP2s. 34 11

We conducted analyses of 1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (1Me3C-THBC) by gas chromatography-mass spectrometry (negative chemical ionization mode) to investigate its presence and the in vivo condensation between tryptophan and AcH. 1Me3C-THBC was found in the cerebellum and the cerebrum of normal rat [117.0 +/- 41.7 and 46.5 +/- 13.9 pmol/g tissue (mean +/- SEM), respectively]. The concentrations of 1Me3C-THBC and tryptophan were higher in the cerebellum than those in the cerebrum. The level of 1Me3C-THBC in both regions remained unchanged following a single oral ethanol administration alone or with cyanamide pretreatment. These data suggest that acetaldehyde is an unlike precursor of 1Me3C-THBC as a result of ethanol ingestion. 1Me3C-THBC also existed in the rat chow (282.0 +/- 24.2 pmol/g), so that most of brain 1Me3C-THBC detected in the rat brain might have originated from dietary sources. However, the possibility of a biosynthesis from tryptophan and alpha-keto acid still remained, especially after long-term ethanol treatment.
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PMID:1-Methyl-tetrahydro-beta-carboline-3-carboxylic acid is present in the rat brain and is not increased after acute ethanol injection with cyanamide treatment. 173 23

1. The role of the median raphe nucleus (MRN) and of increased central serotonin (5HT) synthesis/release in the mediation of Na+ excretion (UNaV) and K+ excretion (UKV) and of urine output (UV) was evaluated for 120 min. 2. Male Wistar rats weighing 220-280 g were used in each group of 12-13 animals. The rats implanted with a cannula in the MRN were injected with saline (0.5 microliters) or with 5.0 and 15.0 ng/0.5 microliters kainic acid (KA), an excitatory amino acid (EAA). Another group of rats was injected ip with 200 mg/kg saline or tryptophan, the initial precursor of 5HT synthesis. 3. Injection of both kainic acid and tryptophan led to increased Na+ excretion, but the magnitude and time course were different for each treatment. 4. Both KA doses were effective in increasing UNaV (0.61 +/- 0.08, mean +/- SEM, and 0.95 +/- 0.19 microEq/min, respectively, vs 0.27 +/- 0.04 microEq/min for saline at 60 min). The effect on UKV was statistically significant with the 15.0 ng dose (0.44 +/- 0.05 microEq/min vs 0.25 +/- 0.03 microEq/min for saline) at 20 min. 5. Tryptophan administration caused an initial gradual increase in UNaV which became steady and significant after 60 min (1.02 +/- 0.15 microEq/min vs 0.36 +/- 0.06 microEq/min for saline), as well as an increase in UKV (0.58 +/- 0.06 microEq/min vs 0.26 +/- 0.04 microEq/min for saline) at 60 min and throughout the remainder of the observation period. 6. KA-induced MRN stimulation and systemic tryptophan overload significantly increased UV at 60, 80 and 100 min (30 to 97% above control values).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Participation of the median raphe nucleus and central serotoninergic pathways in the control of water electrolyte excretion. 179 77

Over a 21-d period, 400 [four rats/level, 10 levels/amino acid, 10 indispensable amino acids (IAA)] male weanling rats (65.9 +/- 0.3 g; mean +/- SEM) were fed diets with one of 10 levels of each of the 10 IAA. In addition, four rats were fed an amino acid-free diet and 16 rats were killed on d 0 for individual body composition. With the exception of the limiting amino acid (LAA), an increment (35% of the requirement) of each IAA was added to the mixture to insure that the LAA remained first limiting. A four-parameter logistic equation was used to describe the nitrogen and weight gain responses of rats to each IAA. Conservation of nitrogen, defined as a predicted y-intercept value greater than the value observed for rats fed an amino acid-free diet (-0.304 +/- 0.023 g N/21 d), was seen when diets devoid of total aromatic amino acids or lysine (-0.062 +/- 0.013 g N/21 d) or histidine, leucine, tryptophan or valine (-0.115 +/- 0.011 g N/21 d) were fed. When total sulfur amino acids were first limiting, diminishing returns (a decrease in the first derivative) was evident from zero intake to Rmax (estimated asymptotic response maximum). In contrast, when other IAA were limiting, diminishing returns were apparent after approximately the first third of the full response. Based on the first derivative of the response curves, the efficiency of nitrogen gain depends on the LAA. The dietary LAA would be expected to influence the shape of the response curve and therefore influence the quantitative aspects of diminishing returns.
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PMID:Use of a four-parameter logistic equation to evaluate the response of growing rats to ten levels of each indispensable amino acid. 194 Nov 79

We investigated the correlation between amino acid level and hepatic graft function. Plasma amino acid levels were measured at three time periods during canine orthotopic liver transplantation. During the anhepatic phase, plasma amino acid levels rose except for tryptophan. Cystine and alanine (Ala) increased significantly to 210 +/- 28% (n = 20, mean +/- SEM) and 203 +/- 11% from preoperative values (100%), respectively. In animals successfully surviving without hepatic insufficiency after transplantation of fresh livers (n = 7), plasma amino acid levels were restored to preoperative values within 3 hr following reperfusion. On the other hand, in animals that died from hepatic insufficiency within 5 days after grafting of warm ischemically damaged livers (n = 8), plasma amino acids, especially Ala, phenylalanine, total free plasma amino acids, and aromatic amino acids progressively increased to 216 +/- 25, 274 +/- 36, 152 +/- 15, and 152 +/- 15% at 3 hr after reperfusion. These were significantly higher compared to those of the group of animals transplanted with fresh livers (P less than 0.01-0.05). Furthermore, higher values were found in those dogs transplanted with warm ischemically damaged livers surviving for shorter periods. Also in dogs that died from hepatic insufficiency within 8 hr after grafting of livers preserved for 24 hr (n = 5), amino acid levels were at high values at 3 hr. These results suggest that in animals having good graft function, plasma amino acid levels are restored to preoperative values by 3 hr after reperfusion. In other cases, primary nonfunction should be strongly suspected after liver transplantation.
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PMID:Evaluation of initial hepatic allograft function with changes of free plasma amino acids in canine orthotopic liver transplantation. 199 Feb 18

Integrity of the hepatic microcirculation and maintenance of endothelial cell viability are critical components in preventing primary non-function after liver transplantation. Therefore, hepatic microcirculation and leucocyte-endothelial interaction were studied in rat livers stored for 1 h in Euro-Collins (EC), University of Wisconsin (UW), and histidine-tryptophan-ketoglutarate (HTK) solutions and subsequently transplanted. One hour after transplantation surgery, the livers were exposed under an intravital fluorescence microscope. After injection of the leucocyte marker acridine orange (1 mumol/kg), six pericentral fields were observed for 30 s and experiments were recorded continuously. The percentage of perfused sinusoids was reduced in the livers in the EC group (82.9%) in contrast to the UW (93.2%) and HTK groups (91.0%). Livers in the EC group showed a reduction in the diameters of pericentral sinusoids (7.3 +/- 0.2 microns; mean +/- SEM) compared with the UW group (9.5 +/- 0.2 microns; P less than 0.05) and HTK group (10.2 +/- 0.8 microns; P less than 0.05), indicating substantial cell swelling in livers stored in EC solution. Permanent adherence of leucocytes was most frequently observed in the EC group (33.5 +/- 1%), while this phenomenon was less pronounced in the UW group (14.5 +/- 1.1%; P less than 0.05) and HTK group (16.3 +/- 0.7%; P less than 0.05). Conversely, temporary adherence of leucocytes was reduced in the EC group (19.7 + 1.3%) compared with the UW group (30.5 + 2.1%) and the HTK group (34.4 + 0.8%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Microcirculatory disturbances and leucocyte adherence in transplanted livers after cold storage in Euro-Collins, UW and HTK solutions. 205 99

The recent recognition of the eosinophilia-myalgia syndrome (EMS) associated with the ingestion of L-tryptophan prompted an analysis of the peripheral blood eosinophil phenotypes and of the serum eosinophil hematopoietins in this disorder. Five patients with an illness characterized by the abrupt onset of aching skeletal muscles, edema, thickening and induration of the skin, and marked blood eosinophilia associated with L-tryptophan ingestion provided eosinophils, serum, or both, for evaluation. Gradient sedimentation density analysis of the peripheral blood eosinophils from four of these patients revealed that 43 +/- 13% (mean +/- SEM) of the cells had converted to the abnormal (hypodense) sedimenting phenotype. When normodense eosinophils from the reference donors were cultured for 3 days in medium supplemented with increasing concentrations of serum from the patients with EMS, their viability increased in a dose-dependent manner to 45%, which was significantly augmented over the effect of normal serum. This eosinophil viability-sustaining activity was inhibited by 76 +/- 7% (mean +/- SEM; n = 3) by the addition of anti-interleukin 5 (IL-5) but not by neutralizing antibodies monospecific for either granulocyte/macrophage colony-stimulating factor (GM-CSF) or IL-3. IL-5, an eosinophilopoietic factor, converts normodense peripheral blood eosinophils in vitro to a hypodense sedimenting form with extended viability and augmented biologic responses to activating stimuli. Thus, the presence of IL-5 in the sera of patients with EMS may contribute to the development and maintenance of the eosinophilia and may regulate the conversion of the peripheral blood eosinophils to the hypodense phenotype with augmented pathobiologic potential.
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PMID:Hypodense eosinophils and interleukin 5 activity in the blood of patients with the eosinophilia-myalgia syndrome. 223 76

The effects of ethanol consumption during pregnancy on maternal, placental, and fetal tissue amino acid levels and metabolism were investigated. Pregnant Sprague-Dawley rats were given 35% ethanol-calorie liquid diet, ad libitum, from gestation day 7 to 21. Control rats were pair-fed with isocaloric sucrose substituted for ethanol. Ethanol consumption decreased fetal body weight and increased placental weight. Twenty-four amino acids were determined in six tissues (maternal plasma and liver, placenta, fetal plasma, liver, and brain) by HPLC with orthophthalaldehyde derivatization. The effects of ethanol on free amino acid levels differed from tissue to tissue. In general, ethanol affected more amino acids in maternal plasma, fetal plasma, and liver. Maternal liver, placenta, and fetal brain amino acids were more resistant to ethanol effect. Two essential amino acids, histidine and tryptophan, were consistently decreased in fetal tissues by maternal ethanol consumption. The values (ethanol vs. control, nmole/ml or g, mean +/- SEM, N = 20) of fetal plasma, liver, and brain for histidine were 51.8 +/- 6.0 vs. 85.3 +/- 4.5 (p = 0.001), 269.0 +/- 26.4 vs. 503.7 +/- 47.3 (p = 0.0004), and 117.9 +/- 7.7 vs. 154.6 +/- 8.7 (p = 0.0055), respectively; and for tryptophan were 105.7 +/- 3.1 vs. 132.2 +/- 4.1 (p = 0.0001), 128.8 +/- 3.7 vs. 144.3 +/- 6.0 (p = 0.0407), and 83.4 +/- 7.2 vs. 103.6 +/- 3.2 (p = 0.0198), respectively. Histidine was also decreased in placenta by ethanol (138.1 +/- 6.6 vs. 189.1 +/- 11.8 nmole/g, p = 0.0014).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Gestational ethanol consumption on tissue amino acid levels: decreased free histidine and tryptophan in fetal tissues with concomitant increase in urinary histamine excretion. 237 28

Levels of whole blood serotonin and tryptophan were measured in 11 human subjects after the consumption of a meal. Blood samples were obtained at 30 and 15 min before the meal and at 15, 30, and 60 min postcibal. One-hour urine specimens were collected for 5 subjects at 0, 60, and 120 min. Whole blood serotonin and tryptophan and urinary 5-hydroxyindoleacetic acid were measured using specific high-performance liquid chromatographic methods. A precibal mean (+/- SEM) serotonin level of 136 +/- 8 ng/ml (n = 22) was observed; means at 15, 30, and 60 min after the meal were 138 +/- 20 ng/ml (n = 9), 145 +/- 18 ng/ml (n = 11), and 138 +/- 16 ng/ml (n = 11), respectively. At no time were postcibal levels of whole blood serotonin significantly higher than baseline levels (paired t-test). Urinary excretion of 5-hydroxyindoleacetic acid also was unchanged; mean hourly rates were 230 +/- 23 micrograms/h before the meal, and 196 +/- 17 micrograms/h and 190 +/- 33 micrograms/h (n = 5) during the first and second hour postcibal, respectively. The absence of a postcibal increase of serotonin in circulating whole blood indicates that serotonin is probably not a human gastrointestinal hormone in the usual sense.
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PMID:Effect of a meal on human whole blood serotonin. 257 39


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