Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “GLUTAMIC ACID”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,639 records · Page 91Linked to original sources

Nasal application of a gel formulation of N-acetyl-aspartyl glutamic acid (NAAGA) compared with placebo and disodium cromoglycate in the symptomatic treatment of pollinosis.

A gel formulation of the antiallergic compound N-acetyl-aspartyl glutamic acid (NAAGA) (Rhinaaxia (R)) has been evaluated in a multicenter, randomized, double-blind, three-arm, parallel-group comparison with placebo gel (P) and disodium cromoglycate (DSCG) in outpatients suffering from seasonal allergic rhinitis (pollinosis). Nose and eye symptoms were assessed daily by the patients on visual analog scales (VAS), and medical examinations were held after 1 week and at the end of the 4-week treatment. The use of rescue medications (H1-antagonist (terfenadine) and soothing eye-drops (Spersallerg) was recorded as a main assessment indicator of efficacy. For the efficacy analysis, only the periods with relevant pollen concentrations (> or = 50 grains/m3) were considered. The study extended over the two pollen seasons 1989 and 1990. Of 230 included patients, 190 were suitable for efficacy analysis (R = 63, P = 64, DSCG = 63). The VAS data did not reveal a difference between the treatment groups for nasal symptoms, whereas the use of terfenadine tablets was significantly lower in the Rhinaaxia group than in either the placebo (P = 0.0001) or DSCG group (P = 0.03). The eye symptoms were significantly less severe in the Rhinaaxia group than in both placebo (P = 0.0001) and DSCG (P < 0.01) groups. In addition, the use of rescue medication was significantly higher in the placebo than in the Rhinaaxia treatment group (P = 0.0001). The incidence of local untoward effects (itching/burning sensation in the nose) was slightly higher in the Rhinaaxia group, while the overall tolerability assessment was similarly good in all three treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗

Congenital encephalomyopathy and adult-onset myopathy and diabetes mellitus: different phenotypic associations of a new heteroplasmic mtDNA tRNA glutamic acid mutation.

We report the clinical, biochemical, and molecular genetic findings in a family with an unusual mitochondrial disease phenotype harboring a novel mtDNA tRNA glutamic acid mutation at position 14709. The proband and his sister presented with congenital myopathy and mental retardation and subsequently developed cerebellar ataxia. Other family members had either adult-onset diabetes mellitus with muscle weakness or adult-onset diabetes mellitus alone. Ragged-red and cytochrome c oxidase (COX)-negative fibers were present in muscle biopsies. Biochemical studies of muscle mitochondria showed reduced complex I and IV activities. The mtDNA mutation was heteroplasmic in blood and muscle in all matrilineal relatives analyzed. Primary myoblast, but not fibroblast, cultures containing high proportions of mutant mtDNA exhibited impaired mitochondrial translation. These observations indicate that mtDNA tRNA point mutations should be considered in the differential diagnosis of congenital myopathy. In addition they illustrate the diversity of phenotypes associated with this mutation in the same family and further highlight the association between mtDNA mutations and diabetes mellitus.

Adult↗

[Effect of hypothermia and hyperoxia on the ammonia-glutamic acid system in the brain of rats].

The content of ammonia, glutamine, dicarboxylic amino acids and GABA was studied in the brain under 1, 2, 4-fold separate and simultaneous effect of hypothermia (19-20 C) and hyperoxia (3 atm.). A two-fold hypothermia of rats is accompanied by a greater increase of ammonia in the brain than a three-fold one. The content of glutamine under two-fold cooling is unchanged and under three-fold cooling it is twice as low as compared to its content in the brain of the control rats. The content of glutamic acid decreased after two-fold hypothermia is almost unchanged by the third seance of hypothermia. The repeated actions of hyperoxia also cause a considerable increase in the ammonia content but the dynamics of changes in the content of the nitrogenous metabolic products is contary to that in animals subjected to repeated seances of hypothermia. A simultaneous combined action of hypothermia and hyperoxia produces no additive effect on the system ammonia-glutaminic acid.

Ammonia↗

Glutamic acid decarboxylase and enkephalin immunoreactive axon terminals in the rat neostriatum synapse with striatonigral neurons.

Synaptic interactions between striatal projection neurons and axon terminals containing immunoreactive glutamic acid decarboxylase (GAD) or Leu-enkephalin were examined in the rat neostriatum using a combined method of horseradish peroxidase retrograde transport from the substantia nigra and immunohistochemistry at the electron microscopic level. Results showed that numerous immunoreactive GAD and enkephalin boutons formed synapses with the cell bodies and dendrites of medium-sized striatonigral neurons. These findings demonstrate that within the neostriatum GABA and enkephalin directly influence caudate output pathways.

Animals↗

Ectopic Purkinje-like cells are GABAergic: immunohistochemistry with an immune serum against glutamic acid decarboxylase.

Intensely stained cells are found in the cerebellar white matter of the vermis and paravermis in adult rats after immunoreaction with an immune serum raised against glutamic acid decarboxylase (GAD). The cells are similar in size to cortical Purkinje cells and three times the size of Golgi cells of the internal granule layer, and have a thick immunopositive cell process emerging from a well-defined cytoplasmic cone. In the cytoplasm, immunoprecipitates are more dense around the nucleus as in normally located Purkinje cells. The morphological appearance of the immunopositive cells suggests that they may be ectopically located Purkinje cells. The soma of the ectopic Purkinje cells is contacted by a few darkly stained terminal boutons. Data indicate that, in spite of the different cellular environment, ectopic Purkinje cells can develop not only the typical morphological pattern already described but also other intrinsic features, such as their typical inhibitory neurotransmitter.

Animals↗

Peculiar labeling of cultured hippocampal neurons by different sera harboring anti-glutamic acid decarboxylase autoantibodies (GAD-Ab).

Immunological derangement is assumed to be present in a subgroup of patients affected by drug-resistant epilepsy with serum harboring anti-glutamic acid decarboxylase autoantibodies (GAD-Ab). To further investigate the specific reactivity of GAD-Ab with target cells, we tested sera from drug-resistant epileptics harboring GAD-Ab on cultured fetal rat hippocampal neurons. As a control, we tested sera from GAD-Ab-negative epileptics and GAD-Ab-positive patients affected by Stiff Person Syndrome (SPS), ataxia or diabetes. A specific pattern of reactivity, varying according to disease, was detected on application of sera from GAD-Ab-positive patients with epilepsy, SPS and ataxia, but no specific labeling was found on application of sera from patients with GAD-Ab-negative epilepsy or from GAD-Ab-positive diabetic controls.

Animals↗

The Caenorhabditis elegans gene unc-25 encodes glutamic acid decarboxylase and is required for synaptic transmission but not synaptic development.

The neurotransmitter GABA has been proposed to play a role during nervous system development. We show that the Caenorhabditis elegans gene unc-25 encodes glutamic acid decarboxylase (GAD), the GABA biosynthetic enzyme. unc-25 is expressed specifically in GABAergic neurons. Null mutations in unc-25 eliminate the UNC-25 protein or alter amino acids conserved in all known GADs, result in a complete lack of GABA, and cause defects in all GABA-mediated behaviors. In unc-25 mutants the GABAergic neurons have normal axonal trajectories and synaptic connectivity, and the size and shape of synaptic vesicles are normal. The number of synaptic vesicles at GABAergic neuromuscular junctions is slightly increased. Cholinergic ventral nerve cord neurons, which innervate the same muscles as GABAergic ventral cord neurons, have normal morphology, connectivity, and synaptic vesicles. We conclude that GAD activity and GABA are not necessary for the development or maintenance of neuromuscular junctions in C. elegans.

Amino Acid Sequence↗

Glutamic acid decarboxylase antibody positivity is associated with an impaired insulin response to glucose and arginine in nondiabetic patients with autoimmune thyroiditis.

To study whether antibodies to glutamic acid decarboxylase (GADab) are associated with subclinical beta-cell damage and impaired insulin secretion, we screened 441 nondiabetic patients with autoimmune thyroiditis (AT) for GADab, and 15 (3.4%) were found positive. Antibodies to IA-2 were found in two GADab+ and one GADab- patients. We matched 11 GADab+ and 13 GADab- AT patients who were euthyroid on thyroxin supplementation, and 13 control subjects for sex, age, and body mass index and measured insulin, C-peptide, and glucagon response to glucose and arginine at three blood glucose concentrations (fasting, 14 mmol/liter, >25 mmol/liter). In the fasting state, all groups had similar blood glucose concentration and HbA1c level, but the serum insulin concentration was higher in the AT patients compared with the control subjects (P < 0.04). The acute insulin response to arginine was lower in GADab+ than in GADab- thyroiditis subjects at glucose concentration of 14 and >25 mmol/liter (AIR(14): 76.8 +/- 52.0 vs. 158.2 +/- 118.2 mU/liter, P = 0.040; AIR(>25): 84.3 +/- 64.4 vs. 167.9 +/- 101.5 mU/liter, P = 0.035). In conclusion, GADab were associated with a decreased insulin secretion capacity in nondiabetic subjects with thyroiditis, which suggests that GADab positivity could be a marker of subclinical insulitis.

Adult↗

Cytotoxic T cells specific for glutamic acid decarboxylase in autoimmune diabetes.

Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease that results in the destruction of the pancreatic islet beta cells. Glutamic acid decarboxylase (GAD) has been recently indicated as a key autoantigen in the induction of IDDM in nonobese diabetic mice. In human diabetes, the mechanism by which the beta cells are destroyed is still unknown. Here we report the first evidence for the presence of GAD-specific cytotoxic T cells in asymptomatic and recent diabetic patients. GAD65 peptides displaying the human histocompatibility leukocyte antigen (HLA)-A*0201 binding motif have been synthesized. One of these peptides, GAD114-123, binds to HLA-A*0201 molecules in an HLA assembly assay. Peripheral blood mononuclear cells from individuals with preclinical IDDM, recent-onset IDDM, and from healthy controls were stimulated in vitro with the selected peptide in the presence of autologous antigen-presenting cells. In three cases (one preclinical IDDM and two recent-onset IDDM), we detected specific killing of autologous antigen-presenting cells when incubated with GAD114-123 peptide or when infected with a recombinant vaccinia virus expressing GAD65. These patients were the only three carrying the HLA-A*0201 allele among the subjects studied. Our finding suggests that GAD-specific cytotoxic T lymphocytes may play a critical role in the initial events of IDDM.

Adolescent↗

Genetic control of immune responses in vitro. I. Development of primary and secondary plaque-forming cell responses to the random terpolymer 1-glutamic acid 60-1-alanine30-1-tyrosine10 (GAT) by mouse spleen cells in vitro.

In vivo, the antibody response in mice to the random terpolymer L-glutamic acid(50)-L-alanine(30)-L-tyrosine(10) (GAT) is controlled by a histocompatibility-linked immune response gene(s). We have studied antibody responses by spleen cells from responder and nonresponder mice to GAT and GAT complexed to methylated bovine serum albumin (GAT-MBSA) in vitro. Cells producing antibodies specific for GAT were enumerated in a modified Jerne plaque assay using GAT coupled to sheep erythrocytes as indicator cells. Soluble GAT stimulated development of IgG GAT-specific plaque-forming cell (PFC) responses in cultures of spleen cells from responder mice, C57Bl/6 (H-2(b)), F(1) (C57 x SJL) (H-2(b/s)), and A/J (H-2(a)). Soluble GAT did not stimulate development of GAT-specific PFC responses in cultures of spleen cells from nonresponder mice, SJL (H-2(s)), B10.S (H-2(s)), and A.SW (H-2(s)). GAT-MBSA stimulated development of IgG GAT-specific PFC responses in cultures of spleen cells from both responder and nonresponder strains of mice. These data correlate precisely with data obtained by measuring the in vivo responses of responder and nonresponder strains of mice to GAT and GAT-MBSA by serological techniques. Therefore, this in vitro system can effectively be used as a model to study the cellular events regulated by histocompatibility-linked immune response genes.

Alanine↗

[Glutamic acid decarboxylase autoantibody concentration and glucose tolerance in late pregnancy].

Genetic and immunological factors may play a role as possible causes for gestational diabetes. Autoantibodies to glutamic acid decarboxylase (GADA) are frequently found in patients with insulin dependent diabetes, but have only rarely been analyzed with regard to the carbohydrate tolerance in pregnancy. An oral glucose tolerance test (oGTT) with 75 g glucose was performed in 110 pregnant patients during the third trimenon. Glucose (glucose dehydrogenase method) and insulin (RIA) concentrations were measured after 0, 30, 60, 120, and 180 minutes. Patients were divided into five groups of increasing glucose intolerance based on the highest glucose concentration reached during the oGTT. GADA were measured using a quantitative enzyme-immunoassay. Only a single patient showed pathologically elevated GADA, and her oGTT results were within the normal range. GADA in subjects with normal pathological glucose tolerance showed no significant difference (276.6 +/- 151.6 and 263.0 +/- 107.1 mU/ml respectively). There was a tendency of positive correlations between high GADA-levels and higher concentrations of insulin as well as an increased insulin-glucose-index. These findings suggest that pregnant patients with higher GADA-levels may have an increased insulin resistance. In conclusion, the concentration of GADA was not found to be helpful in evaluating the current metabolic situation in gestational diabetes. It remains unclear whether elevated GADA during pregnancy have a prognostic value regarding the manifestation of overt diabetes mellitus later in life.

Adult↗

Glutamic-acid-decarboxylase-and parvalbumin-like-immunoreactive structures in the olfactory bulb of the human adult.

This study examines the distribution and morphological characteristics of glutamic-acid-decarboxylase-like (GAD)- and parvalbumin-like (PA)-immunoreactive structures in the olfactory bulb of the human adult. GAD-immunoreactive somata occurred in the glomerular layer, the external granule cell layer, the more superficial portion of the external plexiform layer, and the internal granule cell layer. The cells were small- to medium-sized. Demonstration of lipofuscin pigment revealed the presence of unpigmented as well as pigmented neurons, thus suggesting the existence of two subpopulations of GAD-positive neurons. GAD-immunoreactive puncta and/or fibers were mainly seen in the periglomerular region and the internal granule cell layer. All other layers of the bulb, as well as the intrabulbar portion of the anterior olfactory nucleus, displayed considerably less of these puncta and/or fibers. The olfactory nerve layer remained practically clear of immunoreactive material. PA-immunoreactive somata occurred in the glomerular layer and both the external and internal granule cell layer. Only a small number of immunoreactive nerve cells were encountered within the white matter or the olfactory tract. Most PA-positive neurons displayed characteristics of short axon cells whereas a few others resembled van Gehuchten cells. All of the PA-immunoreactive neurons were devoid of lipofuscin pigment. Immunoreactive puncta and fibers were present in all layers though predominating in the periglomerular region, the olfactory nerve layer, and the internal granule cell layer. The intrabulbar portions of the anterior olfactory nucleus did not show any immunoreactive structures.

Adult↗