Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To evaluate contributions of catecholamines to inhibition of growth during chronic hypoxemia or severe undernutrition, epinephrine (Epi; 0.25-0.35 microg . kg-1 . min-1) or norepinephrine (NE; 0.5-0.7 microg . kg-1 . min-1) was administered to normoxemic fetuses in twin-pregnant ewes for 8-12 days, from 125 to 127 days of gestation. Both had similar effects and decreased fetal weight by approximately 20% relative to control twins (P < 0.01). Weight gain ceased during infusion of Epi or NE (-21 +/- 14.8 or 14 +/- 20.9 g/day), whereas controls gained 93 +/- 13.2 g/day (P < 0.01). Effects on tissues and organs varied, spleen and thymus being most retarded, whereas brain weight and skeletal measures were affected little. Selected muscles from infused fetuses weighed 72% of those in controls. Growth ceased during infusion (P < 0.001). Weight gain of hindlimb bones was negligible, but length increased at 56% of control rates. Arterial blood CO2 and plasma insulin were decreased (P < 0.001), but plasma glucose, growth hormone, and blood oxygenation increased (P < 0.001). Actions of Epi and NE could underlie asymmetrical growth retardation occurring in many adverse physiological situations during fetal development.
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PMID:Catecholamines inhibit growth in fetal sheep in the absence of hypoxemia. 960 6

Ectopic GHRH-secreting tumors, such as carcinoid, rarely cause acromegaly. As protracted exposure to high levels of GH is associated with considerable morbidity and mortality, these patients require early and effective medical therapy to control hormonal hypersecretion. We employed a prolonged release somatostatin analog, lanreotide, to treat a patient with disseminated GHRH-producing carcinoid. Before treatment, the patient had a biochemical profile characteristic of active acromegaly. Plasma GHRH levels were markedly elevated (200-fold), and urinary 5-hydroxyindolacetic acid (5-HIAA) levels were increased (4-fold). Magnetic resonance imaging revealed a large asymmetrical pituitary mass consistent with somatotroph hyperplasia. Somatostatin receptor scintigraphy revealed multiple bony and soft tissue lesions as well as striking pituitary uptake. Lanreotide (30 mg) was administered weekly by im injection for 12 weeks. Rapid and sustained symptomatic clinical improvement with diminished soft tissue swelling and hyperhidrosis was observed. GHRH levels decreased by 70%; glucose-suppressed GH and insulin-like growth factor I levels were reduced by 90% and 75%, respectively, to near normal values; urinary 5-HIAA levels normalized; and the pituitary mass remained unchanged. Unfortunately, the patient died due to complications of osteogenic sarcoma. In conclusion, prolonged release lanreotide induced clinical and biochemical remission in this patient with diffusely metastatic GHRH-producing carcinoid. This long-acting drug thus offers an effective, well tolerated, and convenient medical therapy for control of hormonal hypersecretion induced by excess GHRH.
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PMID:Long-acting lanreotide induces clinical and biochemical remission of acromegaly caused by disseminated growth hormone-releasing hormone-secreting carcinoid. 1032 16

A positron emission tomography (PET) study on the regional cerebral glucose metabolism (rCMRglc) was performed in six patients with corticobasal degeneration (CBD). The clinical features included asymmetrical parkinsonism with apraxia, were related to the cerebral cortical and basal ganglionic dysfunction. An MRI study showed all cases to have asymmetrical atrophy in the front-parietal cortex contralateral to the dominantly affected limb; however, no case was pathologically verified. A PET study revealed three cases to have asymmetrical glucose hypometabolism in the parietal lobe and thalamus, which was compatible with the results of previous reports. However, two patients demonstrated symmetrical glucose hypometabolism in the frontal lobe, striatum and parietal lobe while one case had a diffuse hypometabolism, in spite of a marked asymmetry of the neurological findings. These results therefore suggest the heterogeneity of the glucose hypometabolism in CBD based on the PET findings.
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PMID:Heterogeneity of glucose metabolism in corticobasal degeneration. 987 84

The metabolism of [2,3-13C]succinic acid dimethyl ester ([2,3-13C]-SAD) 10 mmol/L was examined in hepatocytes from overnight-fasted normal rats, 3-day starved rats, and overnight-fasted hereditarily diabetic Goto-Kakizaki (GK) rats. The amount of 13C-labeled succinate, fumarate, malate, lactate, alanine, and aspartate released by the hepatocytes was much higher in fasted normal rats than in starved or diabetic animals. Although the integrated areas of the 13C2 and 13C3 signals assigned to double-labeled malate, lactate, or alanine were not significantly different, the amount of single-labeled malate, lactate, alanine, and aspartate was higher in C3- versus C2-labeled isotopomers. The release of 13C-labeled glucose by the hepatocytes was lower in fasted versus starved or diabetic rats. Virtually all hexose molecules double-labeled in the C1-C2-C3 and/or C6-C5-C4 moieties corresponded to the [1,2-13C] and/or [5,6-13C] isotopomers. However, in the case of the single-labeled species, 13C-labeling of C1 (or C6) exceeded that of C2 (or C5). Both the single- and double-labeled molecules enriched with 13C in the C1-C2-C3 moiety were less abundant than those labeled in the C6-C5-C4 moiety, with such asymmetry being most marked in overnight-fasted normal rats, less pronounced in diabetic animals, and virtually absent in starved rats. These findings document that SAD is efficiently metabolized in hepatocytes, with its use as a gluconeogenic precursor being influenced by the nutritional and hormonal status of the animals. The present experiments also reinforce the view that asymmetrical labeling of glucose by 13C-labeled precursors is modulated by the relative contribution of exogenous and endogenous nutrients to the production of triose phosphates incorporated into the hexose.
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PMID:Effects of starvation and diabetes on the metabolism of [2,3-13C]succinic acid dimethyl ester in rat hepatocytes. 992 Jan 52

Employing Western blot analysis, we investigated the effect of maternal uterine artery ligation causing uteroplacental insufficiency with asymmetrical intrauterine growth restriction (IUGR) upon fetal (22d) and postnatal (1d, 7d, 14d and 21d) brain (Glut 1 and Glut 3) and skeletal muscle (Glut 1 and Glut 4) glucose transporter protein concentrations. IUGR was associated with a approximately 42% decline in fetal plasma glucose (p<0.05) and a approximately 25% decrease in fetal body weights (p<0.05) with no change in brain weights when compared to the sham operated controls (SHAM). In addition, IUGR caused a approximately 45% increase in fetal brain Glut 1 (55 kDa) with no change in Glut 3 (50 kDa) protein concentrations. This fetal brain Glut 1 change persisted, though marginal, through postnatal suckling stages of development (1d-21d), with no concomitant change in brain Glut 3 levels at day 1. In contrast, in the absence of a change in fetal skeletal muscle Glut 1 levels (48 kDa), a 70% increase was observed in the 1d IUGR with no concomitant change in either fetal or postnatal Glut 4 levels (45 kDa). The change in skeletal muscle Glut 1 levels normalized by d7 of age. We conclude that IUGR with hypoglycemia led to a compensatory increase in brain and skeletal muscle Glut 1 concentrations with a change in the brain preceding that of the skeletal muscle. Since Glut 1 is the isoform of proliferating cells, fetal brain weight changes were not as pronounced as the decline in somatic weight. The increase in Glut 1 may be protective against glucose deprivation in proliferating fetal brain cells and postnatal skeletal myocytes which exhibit 'catch-up growth', thereby preserving the specialized function mediated by Glut 3 and Glut 4 towards maintaining the intracellular glucose milieu.
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PMID:Intra-uterine growth restriction differentially regulates perinatal brain and skeletal muscle glucose transporters. 1009 16

The secretion of milk depends on the activity of a large number of membrane transport systems located on the apical and basolateral membranes of mammary secretory cells. It follows that a thorough knowledge of individual mammary tissue membrane transport systems is required if we are to fully understand the process of milk secretion. The distribution of the transporters between the apical and basolateral poles of the mammary epithelium must be asymmetrical given that the mammary gland is capable of vectorial transport. This is particularly evident in the case of glucose and amino acid transport systems: the transport mechanisms for these compounds are predominantly situated in the blood-facing aspect of the secretory cells. In addition. it is apparent that there is a polarized distribution of transport systems (carriers and channels) which accept sodium, potassium, chloride, phosphate, and calcium as substrates.
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PMID:Mammary gland membrane transport systems. 1081 12

Diabetic polyneuropathy is the most frequent neuropathy in western countries. In Germany, there are 3.5 to 4 million diabetic patients. Diagnosis should rule out other polyneuropathies and assess two out of the five diagnostic criteria: neuropathic symptoms, neuropathic deficits, pathological nerve conduction studies, pathological quantitative sensory testing and pathological quantitative autonomic testing. So far, the pathophysiology of diabetic neuropathy remains to be fully understood. Among the various pathophysiological concepts are the Sorbitol-Myo-Inositol hypothesis attributing Myo-Inositol depletion to the accumulation of Sorbitol and Fructose, the concept of deficiency of essential fatty acids with reduced availability of gamma-linolenic-acid and prostanoids, the pseudohypoxia- and hypoxia-hypothesis attributing endothelial and axonal dysfunction and structural lesions to increased oxidative stress and free radical production. Obviously, the hyperglycemia induced generation of advanced glycation end products (AGEs) also contributes to structural dysfunctions and lesions. Elevated levels of circulating immune complexes and activated T-lymphocytes as well the identification of autoantibodies against vagus nerve or sympathetic ganglia support the concept of an immune mediated neuropathy. The reduction of neurotrophic factors such as nerve growth factor, neurotrophin-3 or insulin-like growth factors also seems to further diabetic neuropathy. The symmetrical, distally pronounced and predominantly sensory neuropathy is far more frequent than the symmetrical neuropathy with predominant motor weakness or the asymmetrical neuropathy. The painless neuropathy manifests with impaired light touch sensation, position sense, vibratory perception and diminished or absent ankle deep tendon reflexes. The painful sensory diabetic neuropathy primarily affects small nerve fibers and accounts for decreased temperature perception and paresthesias. The proximal, diabetic amyotrophy evolves subacutely or acutely, induces motor weakness of the proximal thigh and buttock muscles and is painful. Cranial nerve III-neuropathy is also painful and has an acute onset. Truncal radiculopathy follows the distribution of truncal roots and frequently causes intense pain. Autonomic neuropathy occurs with and without somatic neuropathy. The most important therapy is to attempt optimal blood glucose control, to reduce body weight and hyperlipidemia. Symptomatic therapy includes alpha-lipoic acid treatment, as the antioxidant seems to improve neuropathic symptoms. Aldose reductase inhibitors might reduce sorbitol and fructose production and normalize myo-inositol levels. However, there are no aldose reductase inhibitors available in Europe as yet. Evening primrose oil, containing gamma-linolenic acid, might improve nerve conduction velocities, temperature perception, muscle strength, tendon reflexes and sensory function. Substitution of nerve growth factor showed promising results in pilot studies but failed in a large-scale multicenter study. Symptomatic pain treatment can be achieved with tricyclic antidepressants, selective serotonin reuptake inhibitors, anticonvulsants such as carbamazepine, gabapentin or lamotrigine, or anti-arrhythmic drugs such as mexiletine. Topical capsaicin application should reduce neuropathic pain but also induces local discomfort in the beginning of therapy. Vasoactive substances, so far have not proven to be of major benefit in diabetic neuropathy. Physical therapy and thorough footcare are of primary importance and allow prevention of secondary complications such as foot amputations.
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PMID:[Diabetic somatic polyneuropathy. Pathogenesis, clinical manifestations and therapeutic concepts]. 1092 53

Whereas many reports substantiated the suitability of using [2-(13)C]glycerol and Mass Isotoper Distribution Analysis for gluconeogenesis, the use of [(13)C]glycerol had been shown to give lower estimates of gluconeogenesis (GNG). The reason for the underestimation has been attributed to asymmetric isotope incorporation during gluconeogenesis as well as zonation of gluconeogenic enzymes and a [(13)C]glycerol gradient across the liver. Since the cycling of glycerol carbons through the pentose cycle pathways can introduce asymmetry in glucose labeling pattern and tracer dilution, we present here a study of the role of the pentose cycle in gluconeogenesis in Fao cells. The metabolic regulation of glucose release and gluconeogenesis by insulin was also studied. Serum-starved cells were incubated for 24 h in Dulbecco's modified Eagle's media containing 1.5 mm [U-(13)C]glycerol. Mass isotopomers of whole glucose from medium or glycogen and those of the C-1-C-4 fragment were highly asymmetrical, typical of that resulting from the cycling of glucose carbon through the pentose cycle. Substantial exchange of tracer between hexose and pentose intermediates was observed. Our results offer an alternative mechanism for the asymmetrical labeling of glucose carbon from triose phosphate. The scrambling of (13)C in hexose phosphate via the pentose phosphate cycle prior to glucose release into the medium is indistinguishable from dilution of labeled glucose by glycogen using MIDA and probably accounts for the underestimation of GNG using (13)C tracer methods.
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PMID:Loss of [13C]glycerol carbon via the pentose cycle. Implications for gluconeogenesis measurement by mass isotoper distribution analysis. 1096 Apr 76

The effects of mesial temporal (MT) and cerebellar hypometabolism were studied using measures of verbal, visual and motor skill learning. Twelve patients with refractory temporal lobe epilepsy who showed asymmetrical mesial temporal lobe hypometabolism on [18F] fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) were given tests involving 4 consecutive learning trials and a 30-min delayed recall trial. Delayed recognition was also assessed for the words and designs, and skill transfer was evaluated for mirror drawing. Compared to 9 normal control participants, patients with more marked MT hypometabolism on the left had impaired delayed recall of words and patients with more marked MT hypometabolism on the right showed impaired learning of novel designs, but normal retention over delay. Patients were not impaired in their mirror-drawing performance. The findings for MT hypometabolism correspond well to those obtained in other studies where patients have been classified on the basis of side of hippocampal atrophy or temporal lobe excision.
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PMID:The effects of mesial temporal and cerebellar hypometabolism on learning and memory. 1131 Oct 36

Brain capillary endothelial cells form the blood-brain barrier. They are connected by extensive tight junctions, and are polarized into luminal (blood-facing) and abluminal (brain-facing) plasma membrane domains. The polar distribution of transport proteins allows for active regulation of brain extracellular fluid. Experiments on isolated membrane vesicles from capillary endothelial cells of bovine brain demonstrated the polar arrangement of amino acid and glucose transporters, and the utility of such arrangements have been proposed. For instance, passive carriers for glutamine and glutamate have been found only in the luminal membrane of blood-brain barrier cells, while Na-dependent secondary active transporters are at the abluminal membrane. This organization could promote the net removal of nitrogen-rich amino acids from brain, and account for the low level of glutamate penetration into the central nervous system. Furthermore, the presence of a gamma-glutamyl cycle at the luminal membrane and Na-dependent amino acid transporters at the abluminal membrane may serve to modulate movement of amino acids from blood-to-brain. Passive carriers facilitate amino acid transport into brain. However, activation of the gamma-glutamyl cycle by increased plasma amino acids is expected to generate oxoproline within the blood-brain barrier. Oxoproline stimulates secondary active amino acid transporters (Systems A and B(o)+) at the abluminal membrane, thereby reducing net influx of amino acids to brain. Finally, passive glucose transporters are present in both the luminal and abluminal membranes of the blood-brain barrier. Interestingly, a high affinity Na-dependent glucose carrier has been described only in the abluminal membrane. This raises the question whether glucose entry may be regulated to some extent. Immunoblotting studies suggest more than one type of passive glucose transporter exist in the blood-brain barrier, each with an asymmetrical distribution. In conclusion, it is now clear that the blood-brain barrier participates in the active regulation of brain extracellular fluid, and that the diverse functions of each plasma membrane domain contributes to these regulatory functions.
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PMID:The complementary membranes forming the blood-brain barrier. 1248 36


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