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 1,045 records · Page 58Linked to original sources
PubMed1994

Glutamic acid decarboxylase immunoreactivity in some dorsal thalamic nuclei in Crocodilia.

Glutamic acid decarboxylase (GAD) immunocytochemical properties of thalamic nuclei known to project to the telencephalon were investigated in reptiles, Caiman crocodilus and Alligator mississippiensis, by monoclonal antibodies to GAD epitopes designated as GAD-1, GAD-2 and GAD-5. GAD-immunoreactive puncta were observed with all three monoclonal antibodies in the following dorsal thalamic nuclei by avidin-biotin complex methodology: dorsolateralis anterior, dorsomedialis anterior, diagonalis, rotundus, reuniens pars centralis and pars diffusa, and the medialis complex. In general, immunoreactivity to GAD was more robust in Alligator than in Caiman. GAD-2 immunoreactivity was more intense than immunoreactivity to GAD-1 or GAD-5 at similar antibody concentrations in both species. Thalamic nuclei varied in the pattern and intensity of GAD (+)puncta staining in Caiman and Alligator. No GAD-immunoreactive neurons were observed in any of these seven thalamic nuclei with any GAD antibody in either species.

Alligators and Crocodiles↗
PubMed1995

Stimulation of insulin secretion and potentiation of glibenclamide-induced insulin release by the dimethyl ester of glutamic acid in anaesthetized rats.

The dimethyl ester of L-glutamic acid (GME) stimulates insulin release in isolated pancreatic islets and may represent a novel experimental tool in the study of non-insulin-dependent diabetes. In the present study, GME was found both to stimulate insulin secretion and to augment glibenclamide-stimulated insulin release in normal anaesthetized rats. A comparable hierarchy in the magnitude of the secretory response to GME and/or glibenclamide was found in control rats and animals injected with streptozotocin during the neonatal period. In the latter animals, however, the B-cell secretory response was invariably lower than in control animals. It is proposed that GME represents a novel tool to bypass anomalies of glucose transport and metabolism in the beta cell and, hence, to stimulate insulin release and enhance the insulinotropic action of hypoglycaemic sulphonylurea in animal models of non-insulin-dependent diabetes.

Anesthesia, General↗
PubMed1998

A monoclonal antibody-based characterization of autoantibodies against glutamic acid decarboxylase in adults with latent autoimmune diabetes.

Autoantibodies to glutamic acid decarboxylase (GAD) are an important marker of the autoimmune-mediated beta-cell destruction in insulin-dependent (Type I) diabetes. However, these autoantibodies are also found in patients with Stiff-man syndrome (SMS) without onset of diabetes and some diabetic patients who initially present as non-insulin dependent (Type II) diabetes later becoming insulin-dependent, called as latent autoimmune diabetes in adults (LADA). To study the immune response to GAD in these LADA patients a competitive radiobinding assay based on murine monoclonal antibodies recognizing three different GAD regions was performed. The monoclonal antibodies against GAD recognize two different linear epitopes localized at the N- (amino acids 4-17) and C-terminus (amino acids 572-585) and one conformation-dependent epitope region (amino acids 221-442 IDDM-E1) known to be immunodominant for diabetes-associated autoantibodies. All LADA sera (20/20) reduced substantially the 125I-GAD binding of the monoclonal antibodies reactive with the conformation-dependent epitope region IDDM-E1 and only 20% of these sera additionally diminished the 125I-GAD65 binding by those monoclonals reactive with the both linear epitopes. The SMS sera completely abolished the GAD binding of all three monoclonals, reflecting a broader repertoire including an immune response against the IDDM-E1, a conformation-dependent GAD65 epitope region, also revealed if the SMS sera are diluted to equivalent antibody concentrations. In summary, our results show that diabetes-associated GAD autoantibodies even in adult patients with a late autoimmune process preferentially recognize a conformation-dependent middle GAD65 region. An immune response to all three GAD epitope regions is seldom in these LADA patients and only detectable in association with high antibody titres.

Adult↗
PubMed1982

Effects of early monocular deprivation on choline acetyltransferase and glutamic acid decarboxylase in pigeon visual Wulst.

Choline acetyltransferase (ChAT) and glutamic acid decarboxylase (GAD) activities were measured in various visual structures of the pigeon brain after long-term monocular deprivation followed by short-term binocular presence or absence of light stimulation. The short-term phase (45 min) was coupled with a 2-deoxyglucose experiment in order to select the adequate brain samples. After mononuclear deprivation during the first 6-11 months, ChAT activity was higher by 40-60% in the dorsolateral visual Wulst contralateral to the deprived eye, as compared to the other side. In the same structure, animals, either monocularly deprived or undeprived and exposed binocularly to environmental light for 45 min, had higher ChAT activities on both sides than those maintained in the dark. Mononuclear deprivation performed in adult animals did not affect the ChAT activity in visual Wulst. GAD activity was bilaterally decreased in the visual Wulst after early monocular deprivation. These results suggest that early monocular deprivation has an effect on biochemical systems involved in synaptic transmission at selected relays of the visual pathways.

Age Factors↗
PubMed2003

[Quality control of radioligand assay for glutamic acid decarboxylase antibody].

OBJECTIVE: To supply the quality control for glutamic acid decarboxylase antibody (GAD-Ab) measurement using radioligand assay. METHODS: The quality control of GAD-Ab determined with radioligand assay in 83 batches was analyzed. RESULTS: The intra-assay coefficient of variation (CV) was 4.3% to approximately 8.3% and the inter-assay CV was 7.1% to approximately 10.8%. A ratio of signal to noise (S/N) with 15 or more was defined as a valid measurement. Of the 83 batches, 67 batches (80.7%) met with the standard and the other 16 (19.3%) were not qualified. When the results were analyzed according to the season, the failure rate in summer was significantly higher than that in winter (38.5% vs 4.8%, P < 0.05). In addition, the mean value of S/N in summer was significantly lower than that in winter ( 14.1 +/- 7. 3 vs. 21.5 +/- 5.2, P < 0.01). Among the failed batches, 68.8% (11/16) was caused by TBST buffer and 50% (8/16) due to the increased temperature of TBST buffer. Other causes for the failure included the invalidation of reagents for in vitro transcription and translation. CONCLUSION: TBST buffer and other influential factors of radioligand assay in determining GAD-Ab, should be controlled strictly to ensure a reliable and repeatable result.

Autoantibodies↗
PubMed1996

Antibodies to glutamic acid decarboxylase in the prediction of insulin dependency.

Antibodies to glutamic acid decarboxylase (anti-GAD) predict the progression of adults masquerading as NIDDM to insulin dependency and predict the eventual occurrence of IDDM in healthy pregnant women in Finland. Almost 80% of prediabetic and newly diagnosed IDDM cases are positive for anti-GAD. However, approximately 20% of these groups do not have a humoral response to GAD so it cannot be claimed that anti-GAD is the exclusive autoimmune phenomenon. Nevertheless, 94% of children with newly diagnosed IDDM that we studied had an autoimmune response to either GAD, ICA or IAA, singly or in combination. The anti-GAD assay also has a substantial role in the diagnosis and classification of diabetes presenting in adult life since a proportion of adults who present with apparent NIDDM actually have a slowly evolving autoimmune insulitis, a condition we have called latent autoimmune diabetes in adults (LADA). It appears likely that anti-GAD will be predictive for IDDM in both first degree relatives and the general population. As a result of the cost and relative ease of performance, it will provide a practical alternative to ICA, particularly in population screening. Comparisons of testing for anti-GAD and ICA as predictors of IDDM using large population groups are now in progress in our laboratory.

Adult↗
PubMed2000

IgG1 is the dominant subclass of antibody against glutamic acid decarboxylase among type 1 diabetes in Japanese.

Autoantibody against glutamic acid decarboxylase (GADA) is a highly sensitive predictor of insulin-dependency in adult diabetic patients as well as young individuals. A considerable number of diabetics who do not reach the insulin-dependent stage have this antibody. Recently, type 1 diabetes has been thought to be caused by T helper 1 (Thl)-type autoimmunity based on studies in non-obese diabetic mice, but it is still difficult to investigate antigen-specific T-cell function in human type 1 diabetes. We therefore assessed an IgG subclass assay for GADA, which should reflect T-helper function against GAD. Sera from 14 type 1 diabetic patients positive for GADA by radioligand binding assay were tested for the IgG subclass of GADA. The assay was based on an enzyme-linked immunosorbent assay, which showed a good correlation with radioligand binding assay. The sera of all but one of the 14 type 1 diabetic patients (93%) were positive for the IgG1 subclass of GADA. The IgG2 and IgG3 subclasses of GADA were also detected in one diabetic patient each who were also positive for IgG1. The IgG4 subclass was not detected in any of the sera we tested. We concluded that IgG1 is the dominant subclass of GADA in Japanese type 1 diabetic patients.

Adolescent↗
PubMed2001

Cerebellar ataxia with anti-glutamic acid decarboxylase antibodies: study of 14 patients.

BACKGROUND: Antibodies to glutamic acid decarboxylase (GAD-Ab) are described in patients with insulin-dependent (type 1) diabetes mellitus (IDDM), in stiff-man syndrome, and, recently, in a few patients with cerebellar ataxia. OBJECTIVES: To show a link between GAD-Ab and some patients with cerebellar ataxia and to clarify their clinical and immunologic profiles. METHODS: Serum samples were selected from 9000 samples of 4 laboratories. The selection criterion was an immunohistochemical pattern compatible with GAD-Ab that was confirmed by radioimmunoassay. We identified 22 patients with stiff-man syndrome and 14 with cerebellar ataxia and GAD-Ab. RESULTS: Thirteen of the 14 patients with cerebellar ataxia and GAD-Ab were women, and 11 had late-onset IDDM. Patients did not have clinical or radiologic evidence of brainstem involvement. Ten patients had oligoclonal IgG bands in the cerebrospinal fluid, and intrathecal GAD-Ab synthesis was observed in 5 of the 6 patients studied. The level of GAD-Ab of these patients was similar to those with stiff-man syndrome and significantly higher than those with IDDM or with polyendocrine autoimmunity (P<.001). However, the GAD-Ab levels of 6 of the 9 patients with polyendocrine autoimmunity overlapped with those of patients with cerebellar ataxia. CONCLUSIONS: These results suggest a link between high level of GAD-Ab and some cases of cerebellar ataxia, particularly women with IDDM. If high serum levels of GAD-Ab are detected, the cerebrospinal fluid should be evaluated for the presence of oligoclonal IgG bands and intrathecal synthesis of GAD-Ab to further prove an autoimmune origin of the syndrome.

Adult↗
PubMed2006

A highly sensitive immunoassay resistant to autoantibody interference for detection of the diabetes-associated autoantigen glutamic acid decarboxylase 65 in blood and other biological samples.

BACKGROUND: Glutamic acid decarboxylase-65 (GAD65) is a major autoantigen in autoimmune diabetes and is discharged from injured islet beta cells. GAD65 may also be released by transplanted islets undergoing immunological rejection. To test hypotheses regarding the utility of GAD65 as a biomarker for transplant rejection or diabetes-associated islet damage and also regarding the timing and instigators of GAD65 release in humans or animal models, a sensitive assay capable of measuring GAD65 in serum or plasma will be necessary. Ideally, this assay would also be resistant to interference by anti-GAD65 autoantibodies. METHODS: A novel, magnetic bead-based assay was developed based on GAD65 capture by a monoclonal antibody directed to the only region of the protein known not to be significantly targeted by autoantibodies. A subsequent denaturation step allows sensitive immunodetection to proceed using anti-GAD65 polyclonal antibodies that would otherwise potentially be blocked by bound autoantibodies. RESULTS: The GAD65 assay worked equally well with serum and plasma as with a solution of bovine serum albumin (BSA). The limit of blank was 31 pg/mL and did not differ significantly in the BSA solution (27 pg/mL). Mean recovery of GAD65 from the plasma of control subjects and GAD65 autoantibody-positive and -negative subjects with type 1 diabetes was 101 +/- 4.6%, 88 +/- 7.8%, and 99 +/- 7.0% (+/- SEM), respectively. The assay was used to quantify both recombinant GAD65 and the GAD65 content of human and rodent islets and other tissue extracts that were added to human plasma samples. CONCLUSIONS: A sensitive, autoantibody-resistant GAD65 assay has been developed that is compatible with detection in serum and plasma and therefore will likely also work with a variety of other biologic fluids. This assay may enable the use of circulating GAD65 as a biomarker of islet damage or transplant rejection and will facilitate in vivo studies of the pathogenesis of anti-GAD65 autoreactivity.

Autoantibodies↗
PubMed1998

Heterogeneity in the occurrence of a subset of autoantibodies to glutamic acid decarboxylase in autoimmune polyendocrine patients with islet cell antibodies.

Glutamic acid decarboxylase-65 (GAD-65) is a major target for autoantibodies and autoreactive T cells in patients with insulin-dependent diabetes mellitus (IDDM). Autoantibodies to GAD are also found in patients with stiff man syndrome (SMS) or polyendocrine autoimmunity (PE). The epitope specificities of autoantibodies to GAD in IDDM and SMS have been well documented, but the locations of autoantibody epitopes of GAD in PE patients have not been mapped. Thus, the properties of anti-GAD antibodies in PE patients (with or without diabetes) were investigated. The ability of PE serum antibodies to inhibit the binding of the mouse monoclonal antibody, GAD-6, to native GAD in ELISA was determined. For PE patients without diabetes, levels of inhibition of GAD-6 binding ranged from 0% to almost 70% and were unrelated to the level of binding of serum antibodies to GAD (P = 0.351) or to the functional affinities of these antibodies. This suggests differences in the epitope specificities of anti-GAD antibodies in different patients. Levels of inhibition were also unrelated to clinical condition. SMS antibodies showed similar levels of inhibition of GAD-6 binding. Similar analysis was applied to PE patients with diabetes and levels of inhibition of GAD-6 binding to GAD were determined. These ranged from 0% to 80%, and levels of inhibition were similar in samples taken before or after diabetes onset. There was no significant difference between anti-GAD antibodies from PE patients with or without diabetes in the range of abilities to inhibit GAD-6 binding to GAD, although the highest levels of inhibition were given by sera from non-diabetic patients. This raises the possibility of differential expression of subsets of anti-GAD antibodies in progressive versus slow or non-progressive anti-islet autoimmune responses. Serum antibodies of PE and SMS patients did not inhibit the binding of antibodies specific for the extreme C-terminus of GAD, indicating that this is not the site of the epitopes for the patients' antibodies or for GAD-6.

Adolescent↗
PubMed1983

Neural elements containing glutamic acid decarboxylase (GAD) in the dorsal lateral geniculate nucleus of the rat; immunohistochemical studies by light and electron microscopy.

Immunoreactive constituents of the dorsal lateral geniculate nucleus of adult albino rats were examined by light- and electron-microscopy, using the unlabelled antibody enzyme method, following treatment of brain slices with a purified antibody to glutamic acid decarboxylase. The neuropil of the dorsal lateral geniculate nucleus displayed a conspicuous granular immunoreactivity. In addition, the antibody was bound to a class of small neurons of characteristic morphology. These cells possessed few (commonly 2-4) sparsely branched, long dendrites from some of which immunoreactive appendages were traced. Many cells were bipolar in form, and the dendrites of some appeared to be preferentially orientated. The immunoreactive cells closely resembled intrinsic interneurons characterized in previous Golgi studies of this nucleus. By electron-microscopy, immunoreactive presynaptic elements were present both in the extraglomerular neuropil and in the synaptic glomeruli. The former were axon terminals containing flattened synaptic vesicles and making Gray type II axo-dendritic synaptic contact; they appeared to correspond to axon terminals whose origin in the thalamic reticular nucleus has been established in previous studies, but it is possible that some were axon terminals of intrinsic interneurons. The immunoreactive glomerular components also contained flattened vesicles, were presynaptic to presumptive projection cell dendrites, postsynaptic to retinal axon terminals, and participated in triplet (triadic) and other complex synaptic arrangements. They corresponded in all respects to the synaptic portions of the complex dendritic appendages of intrinsic interneurons, identified and characterized in previous studies. The finding that there are high levels of glutamic acid decarboxylase in the cell bodies, dendritic shafts and dendritic appendages of intrinsic interneurons in the dorsal lateral geniculate nucleus of the rat, and in the axon terminals of fibres projecting to this site from the thalamic reticular nucleus, allows us to conclude that the inhibitory inputs to the geniculo-cortical projection cells from both of these sources are probably mediated by gamma-aminobutyric acid.

Animals↗
PubMed1986

Inhibition of microtubule assembly by poly(L-glutamic acid) and the site of its action.

Poly(L-glutamic acid) (PGA) suppresses the polymerization of porcine brain microtubule proteins and induces the depolymerization in vitro in a concentration-dependent manner. The extent of inhibition increases with increasing molecular weight of the PGA tested. A 50% inhibition of the protein polymerization was observed at a PGA (molecular weight = 60,000) to microtubule protein ratio of 0.04 (w/w), and complete inhibition was obtained at a ratio of 0.07. Such an inhibition on the polymerization by PGA is greatly decreased when Mg2+ is present at a higher concentration. The addition of PGA raises the critical concentration of microtubule proteins necessary for assembly. During incubation with PGA, microtubule proteins retain the ability to assemble, i.e., substoichiometric amounts of taxol considerably relieve the inhibition of assembly by PGA. PGA interacts with microtubule-associated proteins (MAPs) preferentially, because the amount of MAPs binding to PGA-Sepharose 4B is much larger than that of tubulin. Tau proteins were observed only in adsorbed fractions, while MAP-2 was present in both unbound and adsorbed fractions.

Animals↗
PubMed1990

Effect of immunization of sexually immature pullets against poly-alpha-L-glutamic acid on long-term fertility.

Poly-alpha-L-glutamic acid (PGA) is a polypeptide synthesized within the upper oviduct and uterovaginal junction of the hen. Sexually immature pullets were immunized against PGA. These virgin pullets, and immunized and non-immunized controls, were inseminated at 25 weeks of age and then monthly throughout a 30-week egg production interval. While birds immunized against PGA were free of PGA as evidenced by an absence of immunoprecipitation when rabbit anti-PGA serum was overlayed with oviduct extract, immunization had no effect on long-term fertility and therefore is unlikely to have an immunosuppressive or antigen-masking biological role with respect to spermatozoa. We suggest instead that PGA could act as a calcium binding protein.

Animals↗
PubMed1999

Biosynthesis and ultrasonic degradation of bacterial poly(gamma-glutamic acid).

A study of the production of poly(gamma-glutamic acid) (PGGA) by Bacillus licheniformis NCIMB 11709 grown on medium E in shake flasks at 30 degrees C is reported. The enantiomeric composition of PGGA was found to be highly sensitive to the concentration of Mn++, especially when the ion is present in small amounts (</= 20 microM). Polymers with D-unit contents ranging from 10 to 90% and Mw between 0.4 and 2.0 million g mol-1 were obtained for [Mn++] ranging from 0 to 1230 microM. Ultrasonic degradation was proven to be an effective method to reduce both the molecular weight and the polydispersity of naturally produced PGGA without disturbing the chemical constitution of the polymer.

Bacillus↗
PubMed1999

Antitumor activity of poly(L-glutamic acid)-paclitaxel on syngeneic and xenografted tumors.

Poly(L-glutamic acid)-paclitaxel (PG-TXL) is a new water-soluble paclitaxel derivative that has shown remarkable antitumor activity against both ovarian and breast tumors. The purpose of this study was to test whether the antitumor efficacy of PG-TXL depends on tumor type, as is the case for paclitaxel, and to test whether paclitaxel-resistant tumors could be responsive to PG-TXL. We evaluated the therapeutic activity of PG-TXL against four syngeneic murine tumors (MCa-4, MCa-35, HCa-1, and FSa-II) inoculated i.m. into C3Hf/Kam mice, a human SKOV3ip1 ovarian tumor injected i.p. into nude mice, and a human MDA-MB-435Lung2 breast tumor grown in the mammary fat pad of nude mice. Two paclitaxel-responsive murine tumors, MCa-4 and MCa-35, showed significant growth delay with PG-TXL given as a single i.v. injection at its maximum tolerated dose of 160 mg of equivalent paclitaxel/kg or even at a lower dose of 120 mg of equivalent paclitaxel/kg. The other two murine tumors, HCa-1 and FSa-II, did not respond particularly well to either of the two agents, although significant growth delay was observed for both tumors with PG-TXL. In mice with SKOV3ip1 tumors, the median survival times for mice treated with PG alone and PG-TXL at doses of 60 or 120 mg of equivalent paclitaxel/kg were 43, 61, and 75 days, respectively; no survival difference was found between paclitaxel-treated and Cremophor vehicle-treated mice. In mice with MDA-MB-435Lung2 tumor, PG-TXL at a dose of 120 mg of equivalent paclitaxel/kg produced regression of the tumor in 50% of the animals, and in the remaining mice, micrometastases in the lung were found only in 25% of the animals. In comparison, treatment with paclitaxel at 60 mg/kg did not result in tumor regression, and the rate of lung metastases was 42%. These results clearly demonstrate that PG-TXL has significant therapeutic activity against breast and ovarian tumors tested in this study. Future studies to elucidate the mechanism of action of PG-TXL and to assess its clinical applications are warranted.

Animals↗
PubMed1998

Post-transplant diabetes with anti-glutamic acid decarboxylase antibody during tacrolimus therapy.

A 54-year-old man undergoing hemodialysis because of end-stage renal failure was transplanted with a cadaver kidney in November 1997. He had no history of diabetes. Tacrolimus was used as the primary immunosuppressant. Three weeks after transplantation, he developed insulin-requiring diabetes mellitus. Anti-glutamic acid decarboxylase antibody was not detected on the third post-operative day, but appeared 4 weeks after transplantation. The recipient had DNA haplotypes that indicated susceptibility to Type 1 diabetes in Japanese subjects. Immunosuppressive therapy was changed from tacrolimus to cyclosporin. Thereafter, titer of anti-glutamic acid decarboxylase antibody disappeared and the patient's insulin requirement was notably reduced. The mechanism underlying the development of diabetes in this case appears to be, in part, direct beta-cell toxicity due to tacrolimus therapy, resulting in secondary beta-cell autoimmunity. This case suggests that tacrolimus therapy after transplantation should be used with caution in patients with genetic susceptibility to Type 1 diabetes.

Antibodies↗
PubMedDate not supplied

[Enzyme activity of glutamic acid metabolism and the Krebs cycle in the brain of rats laser-irradiated against a background of altered adrenoreceptor function].

In the in vivo experiments it was demonstrated that the effect of a helium-neon laser (lambda = 632.8 nm), at the background of altered functional status of adrenoreceptors, changes the activity of some enzymes of the glutamic acid metabolism and the Krebs cycle. This may be attributed to both the direct effect of laser radiation and the indirect effect via the adrenergic system.

Animals↗
PubMed1991

The structural and functional heterogeneity of glutamic acid decarboxylase: a review.

Studies of the GABA-synthetic enzyme glutamate decarboxylase (glutamic acid decarboxylase; GAD; E.C.4.1.1.15) began in 1951 with the work of Roberts and his colleagues. Since then, many investigators have demonstrated the structural and functional heterogeneity of brain GAD. At least part of this heterogeneity derives from the existence of two GAD genes.

Animals↗