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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The recent availability of recombinant human interleukin-2 (RIL-2) has increased interest in the potential clinical use of this lymphokine. We have examined the biologic effects of intermittent bolus and continuous intravenous administration of RIL-2 in rats. The mean (+/- SEM) half-life after an intravenous bolus injection of RIL-2 was determined to be 2.9 +/- 0.5 min (n = 4). The administration of intermittent intravenous bolus injections of RIL-2 of doses up to 10(6) units/kg every other day for 2 weeks was well tolerated without toxicity as determined by organ histology and serum chemistries. The continuous intravenous infusion of RIL-2 through an indwelling external jugular vein catheter was tolerated for 2 weeks at doses less than or equal to 3,000 U/kg/h and was associated with no abnormal serum chemistries or organ pathology. By contrast, animals that received less than 10,000 U/kg/h demonstrated RIL-2 toxicity leading to death of treated rats. Serum chemistries revealed a fourfold increase in serum glutamate oxaloacetic transaminase and serum glutamate pyruvic transaminase. Liver histology revealed hepatocellular necrosis with mononuclear cell infiltration. The thymus was depleted of lymphocytes and lymphoid infiltrates were present in liver, spleen, and lung. This is the first documentation of toxicity secondary to RIL-2 administration and suggests that hepatopathy may be the dose-limiting toxicity accompanying the administration of RIL-2.
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PMID:Toxicity of recombinant human interleukin-2 in rats following intravenous infusion. 387 93

The unidirectional resorption rates of L-glutamate (initial concentrations of 0.07, 0.66, 2.0 or 20.0 mmol X 1(-1)), D-glutamate (0.66 mmol X 1(-1) in the presence or absence of 20 mmol X 1(-1) L-glutamate), and of L-aspartate (0.073, 0.3, 0.66, 2.0 or 5.0 mmol X 1(-1)) were determined in the rat proximal convolution. L-Glutamate resorption was saturable. A permeability coefficient (P) of less than or equal to 20 microns2 X S-1, and a maximum resorption rate (Jmax) of 0.15 +/- 0.015 (SEM) nmol X S-1 X m-1 at a Km of 0.17 +/- 0.025 (SEM) mmol X 1(-1) was obtained for L-glutamate. For L-aspartate, Jmax was 0.13 +/- 0.005 at a Km of 0.1 +/- 0.013. A free flow glutamate concentration profile along the proximal convolution was (I) predicted from these constants and (II) actually measured by means of free flow micropuncture. The data agree very well and show that more than 90% of the filtered load is resorbed within the first third of the proximal convolution. The late proximal and early distal free flow recoveries of L-glutamate amounted to 5.3 +/- 1.7% (SEM) and 6.6 +/- 1.4% of the filtered load, respectively. In contrast to this, unidirectional resorption during the microperfusion of the same tubule section was high: fractional resorption amounted to ca. 96% at 2 mmol X 1(-1) initial L-glutamate. It fell to 35 or 33% respectively if the initial L-glutamate concentration was 20 mmol X 1(-1) or if the resorption of 0.66 mmol X 1(-1) D-glutamate in presence of 20 mmol X 1(-1) L-glutamate was measured. The fractional excretion of endogenous L-glutamate in the final urine amounted to 0.13 +/- 0.012% of the filtered load. It is concluded that L-glutamate and L-aspartate are quickly resorbed in early parts of the proximal convolution (low Km). Saturation already occurs when there is a small increase in the filtered load (low Jmax). The nephron section between the late proximal and early distal nephron sites also reabsorbs "acidic" amino acids. Normally, however, the back leak cancels this out, and net flux becomes zero. Deep nephrons seem to handle amino acids somewhat differently than superficial nephrons do.
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PMID:Kinetics and localization of tubular resorption of "acidic" amino acids. A microperfusion and free flow micropuncture study in rat kidney. 613 64

The development of intraventricular axons in the infundibular recess of the young rat was investigated by correlative scanning and transmission electron microscopy (SEM-TEM). From the fourth through the fifteenth day of life such axons increase steadily in number. During subsequent weeks their number gradually decreases. In animals given monosodium glutamate on the fourth postnatal day there is widespread neuronal necrosis in the arcuate nucleus, and the development of intraventricular axons is greatly reduced. These findings suggest that the axons originate from the neurons of the arcuate nucleus.
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PMID:Effects of monosodium glutamate on the development of intraventricular axons in the rat hypothalamus. 667 14

Mitochondria were isolated from the hepatopancreas of the Florida spiny lobster Panulirus argus using a high osmolarity medium containing 600 mM mannitol, 83 mM sucrose, 5 mM 4-morpholinepropanesulfonic acid, pH 7.6, 0.5% bovine serum albumin (BSA), and 1 mM EDTA. O2 uptake and Ca2+ transport were measured by electrode methods in similar media (plus 4 mM KPi, 3.3 mM MgCl2, and 0.67 mg/ml BSA, with 80 mM KCl replacing a portion of the osmotic support). Substrate-supported respiration was observed to be coupled to phosphorylation of ADP or uptake of Ca2+ ions. State 3 rates (nanogram atoms O X minute-1 X milligram protein-1 +/- SEM (N)) were: 49.2 +/- 3.9 (19), succinate; 30.9 +/- 3.9 (6), DL-palmitoyl carnitine; 29.0 +/- 2.7(9), L-malate; 40.0 +/- 2.3(3), L-glutamate; 27.7 +/- 2.2(5), D-3-hydroxybutyrate; and 26.4 +/- 2.4 (18), L-proline +/- pyruvate. alpha-Glycerol phosphate was not oxidized. Ca2+ uptake driven by succinate oxidation proceeded with Ca:O ratios of 4.0 +/- 0.2 (SEM). Hepatopancreas mitochondria were not uncoupled by Ca2+ uptake in excess of 1100 ng atoms X mg protein-1. Ca2+ efflux could be induced by ruthenium red, indicating the presence of an active Ca2+ cycle. These mitochondria may provide a favorable model system in which to study regulation of the Ca2+ cycle.
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PMID:Respiratory and calcium transport properties of spiny lobster hepatopancreas mitochondria. 687 Feb 85

Cell morphology, glutamic pyruvic (GTP) and glutamic oxalacetic transaminases (GOT) concentrations, and the ability to produce glucose or urea from different substrates (pyruvate, alanine, fructose, lactate and glutamine) were studied in isolated mouse and rat liver cells in the presence of Ca2+ and K+ chelating agents (0.1 M sodium perchlorate and 0.027 M sodium citrate with 1 mg/ml bovine albumin; ionic strength: 0.198, pH: 7.4). The chelating agent is perfused through the portal vein of an in situ liver, at low pressure (8 ml/min) at 20 C for 15 min. Cell dispersion is obtained by cutting liver lobes and "massaging" the tissue with a plastic spatula. Wash and cell concentration may be obtained by sedimentation or centrifugation in Krebs III, glucose 150 mg %, improved with 0.16 M pyruvate, 0.1 M fumarate and 0.16 M glutamate. This procedure furnished 53.06 +/- 3.33 X 10(6) cells, which was highly significant (p less than 0.001) with respect to saline controls: 6.11 +/- 1.91 X 10(6). After staining with Papanicolaou, hematoxylin-eosin, and PAS, the cellular material obtained was classified optically into: normal isolated parenchymal liver cells, hepatocyte clumps, "burst" cells, normal blood or reticuloendothelial cells, cellular debris and non-cellular material. Cell morphology showed that a constant perfusion (8 ml/min) with a minimal mechanical treatment, 82.5% of the liver cells appears normal. Biochemical study showed that transaminases are indeed lost, but this loss is below the amount capable of effecting metabolic blockade (3/4 of transaminases remain in liver cells; GOT in cells: 692 +/- 218; GPT in cells. 264 +/- 94; GOT in supernatant: 152 +/- 29; GPT in supernatant: 79 +/- 12 mUI/10(6) cells, after recovering 60 min at 37 C) (means +/- SEM). Conversion of substrates (sodium pyruvate 10 mM, 20 mM D-L alanine, 10 mM fructose and 20 mM D-L sodium lactate) into glucose was statistically significant with respect to the baseline when the liver cells were isolated and recovered (rat liver cells, basal: 25.37 +/- 3.73; pyruvate: 54.04 +/- 7.98; DL-alanine: 62 +/- 10.07; fructose: 264.67 +/- 20.51; DL-lactate: 78.05 +/- 17.99 mmoles/10(6) cels, means +/- SEM). Urea production from 5 mM DL-glutamine was statistically highly significant to the basal with rat liver cell isolated and recovered (basal: 160.60 +/- 3.76; DL-glutamine: 608.47 +/- 16.15 mmoles/10(6) cells; means +/- SEM). The results obtained suggest that liver cells isolated with Ca2+ and K+ chelating agents used as described above are of value for biochemical studies.
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PMID:Isolation of liver cells with Ca2+ and K+ chelating agents. Biochemistry and cell morphology. 718 90

The histological patterns of supraependymal cell clusters (CC) in rats of different ages (untreated, androgenized, and treated with monosodium glutamate) were investigated with light (LM)-, scanning- and transmission electron microscopy (SEM, TEM). These clusters were a frequent but not a constant finding. In 18 day- and older embryos, CC were always found in the recess of the olfactory bulb immediately prior to its obliteration. All other CC appear in the infundibular recess between the 3rd and the 6th postnatal day. Independent of age, all cell clusters exhibit small aggregates of subependymal tissue protruding through the ependyma. Both neurons (light cells) and neuroglia (dark cells) were found in the CC. By use of SEM, in the region of the infundibular recess it is possible to distinguish four forms of supraependymal cell clusters according to localization, size, number of cells, and presence of intraventricular axons. CC may be 1) receptors or have an additional secretory function; 2) Manifestations of a pathological type of reaction of the ventricular wall; 3) possible excrescences of the neural matrix, or 4) modifications of the ventricular wall in relation to the obliteration of the ventricular recesses. The first two interpretations are not tenable based on the present observations.
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PMID:Supraependymal cell clusters in the rat brain. 724 64

Little is known about the amino acid (AA) biosynthetic capacity and requirements of premature infants. This study assessed the synthesis of seven biochemically nonessential AA from a universal precursor, glucose, in stable, parenterally fed, premature neonates. Seven infants (six boys, one girl) were studied at a mean age of 6.3 +/- 0.6 (SEM) days; mean gestational age was 29.7 +/- 1.3 (SEM) weeks, and mean birth weight was 1,222.8 +/- 176.5 (SEM) grams. All infants were parenterally fed a mixture of 7.5% to 12.5% dextrose and 2.2% Trophamine, with or without lipid. Mean caloric intake was 93 +/- 8.4 (SEM) kcal/kg/d, and total AA intake was standardized at 2.86 g/kg/d AA, plus supplemental cysteine (30 mg/g AA/d). Each infant received a 4-hour continuous, unprimed intravenous infusion of a stable isotope tracer of D(-)[U13C] glucose (200 mg/kg). Blood samples were obtained before and at the end of the infusion. Conversion of the glucose tracer into seven biochemically nonessential AA (cysteine [Cys], proline [Pro], aspartate [Asp], serine [Ser], glutamate [Glu], alanine [Ala], and glycine [Gly]) was assessed by measuring their isotopic enrichment in plasma, using gas chromatography/mass spectrometry (GC/MS), and expressed as mole percent excess (MPE) (mean +/- SEM). The isotopic enrichment of plasma glucose was also measured using GC/MS. Free plasma AA concentrations (mean +/- SD) were measured using an automated amino acid analyzer. Mean MPE for M + 1, M + 2 and M + 3 Cys, and for M + 1 and M + 3 Pro were not significantly different from 0; M + 2 Pro barely achieved statistical significance (P = .048).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Decreased cysteine and proline synthesis in parenterally fed, premature infants. 747 52

Using a controlled cortical impact model of traumatic brain injury (TBI) coupled with tissue microdialysis, interstitial concentrations of aspartate and glutamate (together with serine and glutamine) were assessed in rat frontal cortex. Histological analysis indicated that the severity of injury following severe TBI (depth of deformation = 3.5 mm) was approximately twice that occurring following moderate TBI (depth of deformation = 1.5 mm). Both groups demonstrated significant postinjury maximal increases in excitatory amino acid (EAA) concentration, which were proportional to the severity of injury. The mean +/- SEM fold increase in dialysate concentrations of aspartate was 38 +/- 13 (n = 5) for moderate TBI and 74 +/- 12 (n = 5) for severe TBI. Fold increases in glutamate concentrations were 81 +/- 26 and 144 +/- 23 for moderate and severe TBI, respectively. Although these increases normalized within 20-30 min following moderate TBI, concentrations of aspartate and glutamate took > 60 min to normalize after severe TBI. Changes in levels of nontransmitter amino acids were much smaller. Fold increases for serine concentrations were 4.6 +/- 0.6 and 7.6 +/- 1.7 in moderate and severe TBI, respectively; glutamine concentrations had similar small fold increases (2.6 +/- 0.2 and 4.1 +/- 0.6, respectively). Calculation of interstitial concentrations following severe TBI indicated that aspartate and glutamate maximally increased to 123 +/- 20 and 414 +/- 66 microM, respectively. To determine the extent to which such tissue concentrations of EAAs could contribute to the injury seen in TBI, the EAA receptor agonists N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid were slowly injected into rat cortex. Remarkably similar histological injuries were produced by this procedure, supporting the notion that TBI is an excitotoxic injury.
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PMID:Traumatic brain injury-induced excitotoxicity assessed in a controlled cortical impact model. 750 79

The in vitro and vivo effects of lead on the NMDA-receptors in adult and juvenile mice were studied by means of receptor binding assays. Adult female NMRI-mice received 100 and 1,000 ppm lead as nitrate in their drinking water for 30 and 90 days. Perinatal exposure was achieved by treating gestating mice from the 5th day post conception with 0, 100 or 1,000 ppm lead in their drinking water. Characterization of the NMDA N-methyl-D-aspartate)-receptor was carried out ex vivo using binding studies on homogenates of the forebrain with the non competitive NMDA-antagonist 3H-MK-801. In vitro, complete inhibition of the radioligand binding was found with half maximal inhibiting concentrations (IC50-values) of 19.7 +/- 2.6 microM (SEM) in absence of amino acids and 9.5 +/- 0.9 in presence of glutamate and glycine. These concentrations are in a range which could be achieved in vivo, e.g. the lead content in the forebrain of juvenile mice treated with 1,000 ppm lead was 10.0 +/- 1.8 mumol/kg wet weight. It was speculated that lead binds at the zinc binding site. In the presence of amino acids and divalent cations, such as calcium or magnesium, low lead concentrations lead to a significant increase in receptor affinity. Analysis of the saturation experiments carried out on forebrain homogenates of lead-treated animals showed a slight increase in receptor density of 13 or 15% with an unchanged Kd-value only in the adult animals treated with 100 ppm lead and in absence of stimulating amino acids.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vitro and in vivo effects of lead on specific 3H-MK-801 binding to NMDA-receptors in the brain of mice. 756 90

Amino acids adsorbed onto blood cell membranes represent about 8% of the total amino acids in blood. The aim of this study was to determine the in vitro adsorption kinetics of different amino acids (L-alanine, glycine, L-glutamate, L-glutamine, L-phenylalanine and L-leucine) onto rat erythrocyte membranes and to assess the effect of 24-hr starvation on these adsorption kinetics. Isolated red cell membranes were incubated at 37 degrees C for 10 sec in the presence of 14C-amino acids--with different specific radioactivity--the radioactivity retained in the membrane fraction measured and kinetic parameters of amino acid adsorption determined. With the exception of glutamate, where the adsorption was negligible, all amino acids studied were adsorbed onto isolated red cell membranes, adhering to simple Michaelis-Menten kinetics. Km' values of glycine, phenylalanine and leucine adsorption in control rats (14.7 +/- 3.8 mM, 8.41 +/- 0.95 mM and 4.65 +/- 0.46 mM respectively, SEM, n = 6-8) decreased in response to 24-hr starvation, giving the following values: 0.792 +/- 0.122 mM, 5.32 +/- 0.82 mM and 3.53 +/- 0.31 mM respectively (SEM, n = 6-8), Vmax' value of glycine adsorption of control rats decreased (from 61.0 +/- 15.5 mmol/mol P/sec to 4.25 +/- 0.70 mmol/mol P/sec, SEM, n = 7) and that of leucine increased (from 13.5 +/- 1.0 mmol/mol P/sec to 18.9 +/- 2.0 mmol/mol P/sec, SEM, n = 7) as an effect of 24-hr starvation. This study shows that alanine, glycine, glutamine, phenylalanine and leucine, but not glutamate, adsorbed onto erythrocyte membranes according to Michaelis-Menten-like kinetics.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vitro adsorption of amino acids onto isolated rat erythrocyte membranes. 758 9


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