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PubMed1983

Evidence for the vitamin K-dependent gamma-carboxylation of the first glutamic acid residue in peptide substrates containing a diglutamyl sequence.

The peptide substrate commonly used in vitamin K-dependent carboxylation, Phe-Leu-Glu-Glu-Val, has been shown, by the use of high-voltage paper electrophoresis, to be degraded from the N-terminus by a microsomal leucine amino-peptidase. The replacement of phenylalanine with a N-t-butoxycarbonyl group resulted in a tetrapeptide substrate with a blocked N-terminus resistant to enzymic degradation. Vitamin K-dependent carboxylation of this non-degradable substrate gave a unique carboxylated product, which was separated from microsomal protein and unchanged substrate by using DEAE-Sephadex A25 as a final step. The carboxylated product was subsequently decarboxylated in 2HCl and analysed by using g.l.c. coupled to a mass spectrometer. This showed that only the first glutamic acid residue in the peptide substrate was carboxylated.

Animals↗
PubMedDate not supplied

Frequency of glutamic acid decarboxylase autoantibodies in Mexican diabetic children.

OBJECTIVE: Use radio binding assay (RBA) to quantify the frequency of autoantibodies to glutamic acid decarboxylase in Mexican children with type 1 diabetes mellitus (DM 1). RESEARCH DESIGN AND METHODS: GAD antibodies were measured in 140 mestizo children with DM 1, 66 female (47.14%) and 74 male (52.8%); age 11.7 +/- 3.55 years, and range 1.10 to 18.5 years. Most patients were treated with intermediate acting insulin, and some with the former combined with regular insulin. Mean disease duration was 3.11 +/- 2.94 years, and range 1 month to 14.5 years. Once the signed written consent was obtained, a 5.0-mL blood sample was drawn, immediately centrifuged, and the serum was kept frozen to -20 degrees C until RBA evaluation was performed with a commercial kit. RESULTS: The anti-GAD was positive in 76 DM 1 patients (54.28%) with values from 1.11 to 156.73 U/mL, and negative in 64 (45.71%). In 19 positive anti-GAD patients, the test was repeated and levels were found between 1.38 and 156.62 U/mL. An initial control group consisting of 25 healthy non-related volunteers matched by sex and age, showed negative anti-GAD for all. CONCLUSIONS: The frequency of anti-GAD in these patients was lower than that of the DM 1 European patients, but similar to that of Asians. This supports the heterogeneity of the etiopathogenic factors of DM 1 in different ethnic groups.

Adolescent↗
PubMed1994

High prevalence of autoantibodies to glutamic acid decarboxylase in long-standing IDDM is not a marker of symptomatic autonomic neuropathy.

Immune reactivity to the enzyme glutamic acid decarboxylase (GAD), a pancreatic islet autoantigen, is present at the diagnosis of insulin-dependent diabetes mellitus (IDDM). Because GAD is also highly expressed in the nervous system, we investigated the presence of autoantibodies to the isoform GAD65 in patients with diabetic neuropathy, which is a debilitating complication of the disease. We studied 39 patients with autonomic and somatic neuropathy, 28 patients matched for age and IDDM duration, and 13 patients with a shorter duration of IDDM, all with no diabetic complications, as well as 50 recently diagnosed diabetic patients, 23 neurologic patients with idiopathic autonomic failure unrelated to IDDM, and 72 healthy subjects. An immunoprecipitation radioligand assay was used to detect anti-GAD65 autoantibodies with in vitro transcribed and translated human islet GAD65 as antigen. Autoantibodies to GAD65 were present in 56% of the diabetic patients with neuropathy, 57% of the long-duration and 69% of the short-duration diabetic control subjects, 78% of the recently diagnosed patients, and 13% of the nondiabetic neuropathic patients. Among the diabetic patients with neuropathy, there was no correlation between the presence of anti-GAD65 antibodies and the presence of autoantibodies to sympathetic ganglia, vagus nerve, or adrenal medulla structures identified by immunofluorescence. Our study shows that anti-GAD65 antibodies are present in a high proportion of patients with diabetic neuropathy but are not exclusively associated with it, rendering it unlikely that they have a role as a disease marker or that they are pathogenetic.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2004

Epitope-restricted 65-kilodalton glutamic acid decarboxylase autoantibodies among new-onset Sardinian type 2 diabetes patients define phenotypes of autoimmune diabetes.

The 65-kDa glutamic acid decarboxylase (GAD65) autoantibodies (GAD65Abs), commonly found in type 1 diabetes mellitus (T1DM) patients, are also found at lower frequencies in type 2 diabetes mellitus (T2DM) patients. GAD65Abs in T1DM patients are epitope specific, in contrast to those found in other GAD65Ab-positive individuals, including T2DM patients. Our aim was to assess whether epitope-specific GAD65Abs, or the additional presence of islet antigen 2 (IA-2) autoantibodies, better define T1DM phenotypes among T2DM patients. GAD65 and IA-2 autoantibodies were analyzed in 1436 Sardinian subjects classified with T2DM and in 384 nondiabetic patient controls. Autoantibody binding specificity to the N-terminal, middle (M), and C-terminal (C) portions of the GAD65 molecule was evaluated. Among the T2DM patients, 5.1% had GAD65 (P < 0.001) and 2.4% had IA-2 autoantibodies, compared with 1.3 and 1.6%, respectively, among the controls. GAD65Ab-positive T2DM patients with M+C (epitope-specific) reactivity were found to have the lowest body mass index (P < 0.001), followed by GAD65Ab/IA-2Ab-positive patients (P < 0.01), and non-M+C-reactive (non-epitope-specific) patients (P < 0.02). In GAD65Ab-positive T2DM patients, c-peptide levels were lower in M+C-reactive compared with non-M+C-reactive patients. Sardinian T2DM patients with M+C-predominant GAD65Ab reactivity have clinical features more similar to those of T1DM patients. Thus, GAD65Ab epitope analysis may help to define T1DM phenotypes among newly diagnosed GAD65Ab-positive patients classified with T2DM.

Adult↗
PubMed1997

Autoantibodies to glutamic acid decarboxylase in three patients with cerebellar ataxia, late-onset insulin-dependent diabetes mellitus, and polyendocrine autoimmunity.

BACKGROUND: Glutamic acid decarboxylase (GAD) is the main target of humoral autoimmunity in stiff-man syndrome (SMS) and insulin-dependent diabetes mellitus (IDDM). GAD autoantibodies (GAD-Abs) are reported in a few patients with cerebellar ataxia, but their relevance is unclear. We describe three patients with cerebellar ataxia and GAD-Abs. METHODS: GAD-Abs were assayed by radioimmunoassay (RIA) and immunohistochemistry and confirmed by immunoblot of recombinant human GAD65. The GAD-Ab levels of the three patients with cerebellar ataxia were compared with those of five with SMS, 49 with IDDM, 64 with cerebellar ataxia of probable degenerative origin without associated autoimmune features, 14 non-IDDM islet cell antibody-positive first-degree relatives of IDDM patients, and 91 normal subjects. RESULTS: The three patients with ataxia and GAD-Abs were women (mean age, 63 years) with an isolated progressive cerebellar disorder, family history of IDDM, late-onset IDDM, and several positive serum organ-specific autoantibodies. Two patients had autoimmune thyroiditis, and one had pernicious anemia. CSF analysis demonstrated oligoclonal IgG bands and intrathecal synthesis of GAD-Abs. By RIA, GAD-Ab titers from the three patients were similar to those of SMS and significantly higher, without overlap, than the titers of IDDM patients. GAD-Abs were absent in the 64 patients with cerebellar ataxia and no evidence of autoimmune disorders. CONCLUSIONS: These findings suggest a link of GAD autoimmunity not only with SMS but also with cerebellar dysfunction. GAD-Abs should be sought in patients with cerebellar ataxia who have late-onset IDDM and other organ-specific autoimmune manifestations.

Adolescent↗
PubMedDate not supplied

Glutamic acid decarboxylase and islet cell antibodies in healthy Estonian children.

The prevalence of antibodies to the 65 kDa isoform of glutamic acid decarboxylase (GADA) was compared with that of islet cell antibodies (ICA) in 614 non-diabetic Estonian children (314 males) aged 3-18 years representing the general population. GADA were analyzed with a radioligand assay, and ICA with a standard immunofluorescence method with a detection limit of 2.5 Juvenile Diabetes Foundation (JDF) units. Fourteen subjects (2.3%, 95% confidence interval [CI] 1.1-3.5%) tested positive for GADA (median level 10.8 relative units [RU], range 7.7-154.2 RU), while 10 (1.6%, CI 0.6-2.6%) had ICA (median levels 34 JDF units, range 3-97 JDF units). Five subjects (0.8%, CI 0.1-1.5%; p = 0.03 vs GADA and 0.15 vs ICA) were double positive. The individual with the second highest GADA level (129.3 RU) and the highest ICA level (97 JDF units) presented with type 1 diabetes 4 months later. A follow-up sample was obtained approximately 3-4 years after the first sampling in 14 subjects initially positive for ICA and/or GADA. Four of the nine initially ICA-positive children remained positive, but their levels decreased from a median of 42 to 18 JDF units (p = 0.06). Only two of the nine retested subjects initially positive for GADA remained positive in the second sample. These observations suggest that the prevalence of GADA in non-diabetic children is of the same magnitude as that of ICA. Combined positivity for both GADA and ICA is less prevalent than single antibody specificities, indicating that double autoantibody positivity may have a higher predictive value for future type 1 diabetes in the general population than either antibody separately. The evanescent character of diabetes-associated autoantibodies in a proportion of the unaffected children implies that more subjects may experience self-restricted beta-cell damage than the number progressing to actual disease.

Adolescent↗
PubMed1995

Autoantibodies to glutamic acid decarboxylase in patients with autoimmune thyroid disease: relation to competitive insulin autoantibodies.

We evaluated the presence of autoantibodies to glutamic acid decarboxylase (GAD), competitive insulin autoantibodies (IAA) and islet cell antibodies (ICA) in sera from 288 non-diabetic patients with autoimmune thyroid disease (AITD), including 212 patients with Graves' disease and 76 with Hashimoto's thyroiditis, and in 235 age- and sex-matched healthy control subjects. GAD antibodies and IAA were assayed using radioimmunoassay with 125I-labelled purified pig brain GAD and human insulin, respectively. Titers of greater than 4.7 units for GAD antibodies and 50 nU/ml for IAA, respectively, the mean + 3SD of 235 age- and sex-matched healthy individuals, were defined as positive. The mean titers of GAD antibodies in patients with Graves' disease and in patients with Hashimoto's thyroiditis were 3.6 +/- 4.6 (mean +/- SD, range 0.6-52.0) units and 3.2 +/- 1.4 (range 0.6-10.0) units, respectively. Titer of GAD antibodies in patients with AITD was significantly higher than in healthy controls (P < 0.0005). Thirteen of 212 (6.1%) patients with Graves' disease and 6 of 76 (7.9%) patients with Hashimoto's thyroiditis had positive GAD antibody titers, whereas titers in healthy control sera were < 4.7 units in all but two individuals (P < 0.005). In competition analysis with purified unlabelled GAD, binding tracer was inhibited in all of 13 GAD antibody-positive Graves' sera and 5 of 6 GAD antibody-positive sera from patients with Hashimoto's thyroiditis. Eight of 212 (3.8%) patients with Graves' disease and 3 of 76 (3.9%) patients with Hashimoto's thyroiditis, but none of healthy controls had IAA levels exceeding the range for normal controls (P < 0.005). Positive IAA levels ranged between 50 and 2383 nU/ml. Strikingly, all of 19 GAD antibody-positive sera were negative for IAA. ICA were not detected in any of the patients or healthy controls. These data demonstrate that GAD antibodies in sera of AITD patients are of low titer but significantly elevated compared to healthy controls, and are independent of the appearance of IAA. They also indicate that, in patients with AITD, an autoimmune response to GAD may occur with no relationship to production of IAA.

Adult↗
PubMed1996

Islet cell antibodies and antibodies against glutamic acid decarboxylase in newly diagnosed adult-onset diabetes mellitus.

This study aimed to determine the prevalence of antibodies against glutamic acid decarboxylase (anti-GAD) and islet cell antibodies (ICA) in relation to beta-cell function in adults newly-diagnosed with diabetes mellitus. beta-cell function was assessed in adults aged 25-70 years newly-diagnosed with diabetes mellitus (n = 84) and control subjects (n = 34) using a 1.6 MJ mixed meal test procedure. beta-cell function was evaluated by the true insulin (defined as immunoreactive insulin minus proinsulin) response to the mixed meal test. Subjects were classified on the basis of the area under the true insulin curve (normal 16830-107700 pmol min/I) and the sum of the 30 and 60 min incremental response (normal 285-3295 pmol/I). The prevalence of anti-GAD and ICA was determined using radioimmunoprecipitation and indirect immunofluorescence, respectively. Twelve (14%) of the study cohort were insulin deficient showing little or no true insulin release. Of the insulin deficient individuals, seven (58%) subjects were anti-GAD antibody positive, compared with eleven (15%) of the subjects without insulin deficiency (P < 0.001). Seven (58%) insulin deficient subjects were ICA positive, whereas only two (3%) non-insulin deficient subjects were ICA positive (P < 0.001). Eight (67%) of the insulin deficient individuals had anti-GAD or ICA, compared with twelve (17%) of those who were not insulin deficient (P < 0.001). The positive predictive values for insulin deficiency of anti-GAD and ICA were 39 and 78% respectively. The sensitivity of both antibodies for detecting insulin deficiency was 50%. The specificity for detecting insulin deficiency was 85% for anti-GAD and 97% for ICA. Positivity for both anti-GAD and ICA gave a specificity and positive predictive value for insulin deficiency of 99%, and a sensitivity of 50%. Nearly one in seven adults presenting with diabetes mellitus as a new diagnosis are insulin deficient using our criteria. Loss of beta-cell function in two thirds of individuals who are insulin deficient can be identified by anti-GAD and ICA. Early detection of these immune markers of beta-cell damage creates the potential for immune modulation to limit such damage.

Adult↗
PubMed1973

Glutamic acid decarboxylase in spores of Bacillus megaterium and its possible involvement in spore germination.

Spores of Bacillus megaterium were examined for glutamic acid decarboxylase (GAD). Although dormant spores showed no GAD activity, spores given sonic treatment and heat-activated spores had high activities when assayed for this enzyme. Several parameters of GAD in heat-activated spores were examined. The effects of KCN, NaN(3), 2,4-dinitrophenol, and KF on GAD activity were examined. Only KCN was an effective inhibitor of GAD activity in heated spores and was also shown to be the only effective inhibitor of GAD activity in vegetative bacteria. Similar patterns of inhibition were obtained with GAD activity and with spore germination, KCN being the only effective inhibitor of both, although at different concentrations. Spore GAD activity in heat-activated spores showed a loss with storage at 4 C; on the other hand, storage at 25 C was not accompanied by a loss, but, to the contrary, showed an increase in GAD activity of about 30%. A comparison of GAD activity at different times during germination, growth, and sporulation showed it to be highest in freshly germinated spores. Although vegetative cells contained GAD activity, the level in log-phase cells was approximately one-half the level obtained with freshly germinated spores. Heat-activated mutant spores with a requirement of gamma-aminobutyric acid for germination gave no GAD activity. GAD activity appeared in mutant spores after germination and increased to levels comparable to parent spores after 9 min of germination.

Aminobutyrates↗
PubMed1994

Comparative localization of two forms of glutamic acid decarboxylase and their mRNAs in rat brain supports the concept of functional differences between the forms.

Two isoforms of glutamic acid decarboxylase (GAD67 and GAD65) and their mRNAs were localized in the rat brain by immunohistochemistry and nonradioactive in situ hybridization methods with digoxigenin-labeled cRNA probes. In most brain regions, both GAD isoforms were present in neuronal cell bodies as well as axon terminals. A few populations of neurons, such as those in the reticular nucleus of the thalamus, exhibited similar cell body labeling for both GADs. However, in many brain regions, the cell bodies that were immunoreactive for GAD67 were often more numerous than those that were immunoreactive for GAD65. In contrast, the density (quantity) of GAD65-immunoreactive axon terminals was higher than that of GAD67-immunoreactive terminals. Strong parallels were observed between the intensity of immunohistochemical labeling of cell bodies and the levels of mRNA labeling for both GAD isoforms. Many groups of GAD-containing cell bodies were distinctly labeled for GAD67, and these same groups of neurons were heavily labeled for GAD67 mRNA. Such neurons included Purkinje cells of the cerebellar cortex, nonpyramidal cells in the cerebral cortex, and neurons of the reticular nucleus of the thalamus. Similar parallels in labeling were observed for GAD65 and its mRNA. Distinct cell body labeling for the protein and associated high levels of GAD65 mRNA were found in neurons of the reticular nucleus of the thalamus and periglomerular cells in the olfactory bulb. However, many cell bodies were not readily labeled for GAD65 with immunohistochemical methods. Such absence or weakness of cell body labeling for the protein was associated with low or moderate levels of GAD65 mRNA. Even though light cell body staining was frequently observed for GAD65 and its mRNA, strong axon terminal labeling for GAD65 was present. Thus, in the deep cerebellar nuclei to which the Purkinje cells of the cerebellar cortex project, strong terminal labeling was observed for both GAD isoforms even though only light cell body labeling of the Purkinje cells was obtained for GAD65 and its mRNA. The findings suggest that the two isoforms of GAD are present in most classes of GABA neurons but that they are not similarly distributed within the neurons. GAD67 is present in readily detectable amounts in many GAD-containing cell bodies whereas GAD65 is particularly prominent in many axon terminals. In addition, neurons that express either form of GAD mRNA also express the corresponding protein. Levels of labeling for the GAD mRNAs suggest that, under normal conditions, the synthesis of GAD65 is frequently lower than that of GAD67.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Postnatal development of the inferior olivary complex in the rat: IV. Synaptogenesis of GABAergic afferents, analyzed by glutamic acid decarboxylase immunocytochemistry.

The postnatal maturation of the GABAergic innervation of the rat inferior olive was studied with an antiserum to glutamic acid decarboxylase (GAD), the GABA-synthesizing enzyme. GAD-positive axons were present at a very low density in the periolivary and interlamellar regions of newborn rats, as well as in certain precise areas of the lamellae, at the mediodorsal limit. The immature distribution indicates that the GABAergic projections reach the inferior olive shortly before birth and that the greater part of synaptogenesis and the establishment of the adult organization occurs postnatally. Light and electron microscopic analyses disclosed that the maturation of this system of olivary afferents passes through three well-defined stages: (1) During the first, or immature stage (from PO to P5), GAD immunoreactivity is not confined to axon terminals, as in adult rats. The labeled fibers penetrate progressively into the periphery of the lamellae and reach their centers in an irregular manner by the end of the immature stage. This staggered invasion of the lamellae accentuates intraregional olivary differences and begins to take the adult configuration. As fiber penetration advances, the density of labeled axons establishing synaptic contacts increases, while the number of completely immunostained fibers decreases. This distribution prevails until the end of the immature stage and suggests that the GABAergic afferent projections remain in a "waiting compartment" from their prenatal arrival until the moment they invade the olivary parenchyma. (2). The second stage is designated as an intermediate stage of maturation and lasts from P7 to P10. During this period, GAD axoplasmic compartmentation occurs, and henceforth only axon terminals exhibit GAD immunoreactivity. Concomitantly, intraregional differences in the pattern of innervation become more marked, because of the continuing irregular distribution of the growing labeled axons. This intermediate maturational stage is also characterized by a rapid increase in labeled axon terminals bearing synaptic complexes and by the formation of complex synaptic arrangements, the protoglomeruli. From the beginning of protoglomeruli formation, GAD-positive axon terminals are one of their constituents, and they are systematically localized at the periphery of the incipient dendritic protrusions. (3) The final stage of maturation takes place from P10 to P15. During this stage, the adultlike pattern of GABAergic innervation of the inferior olive is attained. Toward P15, intraregional differences in GAD immunoreactivity are similar to those of the adult rat.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Catecholaminergic neurons containing GABA-like and/or glutamic acid decarboxylase-like immunoreactivities in various brain regions of the rat.

The coexistence of immunoreactivities for tyrosine hydroxylase (TH) and glutamic acid decarboxylase (GAD) and/or gamma-aminobutyric acid (GABA) was revealed in various brain regions in colchicine-injected and untreated rats, using the peroxidase-antiperoxidase method. Consecutive 40 micron thick Vibratome sections were incubated in different antisera and those cells which were bisected by the plane of sectioning so as to be included at the paired surfaces of two adjacent sections were identified. The coexistence of the immunoreactivities for TH and GAD or GABA in the same cell could thus be determined by observing the immunoreactivity of the two halves of the cell incubated in two different antisera. In the olfactory bulb, retina, diencephalon, mesencephalic central grey and cerebral cortex, many TH-like immunoreactive neurons also showed GAD-like or GABA-like immunoreactivity, whereas in the substantia nigra, ventral tegmental area and locus ceruleus none of TH-like immunoreactive neurons showed either GAD-like or GABA-like immunoreactivity. In the olfactory bulb, retina and cerebral cortex, the majority of the TH-like immunoreactive neurons were also GAD-like or GABA-like immunoreactive. In the diencephalon of colchicine-injected rats, at least one-third of the TH-like immunoreactive neurons were GAD-like immunoreactive. Using serial 0.5 micron thick plastic-embedded sections, it was shown that immunoreactivities for three antigens, GAD, GABA and TH could occur in the same neurons in the olfactory bulb. These observations indicate the possible coexistence of two classical transmitters. GABA and catecholamine, in various brain regions of the rat.

Animals↗
PubMed2002

Enantioselective binding and stable encapsulation of alpha-amino aids in a helical poly(L-glutamic acid)-shelled dendrimer in aqueous solutions.

A novel water-soluble peptide-shelled dendrimer containing a poly(L-glutamic acid) segment grafted on the third-generation poly(amido amine) dendrimer was successfully synthesized, and its secondary structural properties and interaction with alpha-amino acids (Trp, Phe, and Tyr) were revealed by spectroscopic measurements. In the lower pH region, this peptide-dendrimer adopted an alpha-helix conformation with almost 100 % helicity resulting from the three-dimensional aggregation of the segment. Interactions with alpha-amino acids proceeded with positive cooperativity on the basis of a Hill plot, and as a result, D isomers preferentially bound to the alpha-helical segments relative to L isomers. The bound alpha-amino acids were not released into the water phase but were transferred into the inner core of the dendrimer where they remained stable, even when a conformational change of the helix segment was caused by pH variation.

Amino Acids↗
PubMed1992

Secretory expression of a glutamic-acid-specific endopeptidase (SPase) from Staphylococcus aureus ATCC12600 in Bacillus subtilis.

In order to obtain a large quantity of glutamic-acid-specific endopeptidase of Staphylococcus aureus ATCC12600 (SPase) without cultivating its pathogenic host bacterium, expression plasmids enabling secretion of SPase from Bacillus subtilis were constructed by inserting the SPase gene into B. subtilis-Escherichia coli shuttle vectors. B. subtilis harbouring a simple recombinant plasmid containing the coding and the 5'-flanking regions of SPase in the shuttle vector pHY300PLK secreted 22 mg/l of SPase into the medium. As this level was lower than that of the natural strain (45 mg/l), we tried to increase the expression level by constructing a series of hybrid plasmids with the following features: (1) the terminator sequence of the alkaline protease gene from B. subtilis, (2) the promoter and the leader sequences of the alpha-amylase gene or of alkaline protease gene from B. amyloliquefaciens, (3) the vector pHY300PLK and the fused vector of pHY300PLK and pUB110. By using a variety of hybrid plasmids, the resulting transformants secreted SPase at levels of 33-120 mg/l. The recombinant SPase isolated from the medium was indistinguishable from the natural one with respect to its behaviour on sodium dodecyl sulphate-polyacrylamide gel electrophoresis and Western blotting as well as its enzyme activity.

Amino Acid Sequence↗
PubMed1998

N-acetyl-aspartyl-glutamic acid inhibits cellular recruitment and mediator release during the late allergen-induced nasal reaction.

OBJECTIVE: N-acetyl-aspartyl-glutamic acid (NAAGA) was effective in the treatment of allergic rhinitis, with an action on early allergen-induced nasal symptoms and mediator release. The aim of this study was to evaluate the clinical activity of NAAGA and its effects on the late antigen-induced reaction in the nose. METHODS: Ten patients with allergic seasonal rhinitis were included in this randomized double-blind crossover trial of a 6% wt/vol solution of NAAGA (daily dosage 84 mg) versus placebo (lactose). The drug and placebo were administered intranasally five times daily for 1 week, with a 2-week interval between treatments. RESULTS: Treatment with NAAGA, but not with placebo, significantly reduced the late antigen-induced nasal symptoms, mainly nasal obstruction. Eosinophil numbers in the nasal lavages collected 6 h and 24 h after challenge were significantly lower after NAAGA than after placebo. Active treatment also significantly reduced the neutrophil count 6 h after antigen challenge, and significantly lowered eosinophil cationic protein and myeloperoxidase levels in nasal lavages 6 h and 24 h after antigen challenge. CONCLUSION: These results indicate that treatment for 1 week with NAAGA can reduce the late antigen-induced reaction in the nose. This is accompanied by a reduction in eosinophil and neutrophil recruitment and release of eosinophil cationic protein and myeloperoxidase.

Adult↗
PubMed2001

The production of poly-(gamma-glutamic acid) from microorganisms and its various applications.

This review article deals with the chemistry and biosynthesis of poly-(gamma-glutamic acid) (gamma-PGA) produced by various strains of Bacillus. Potential applications of gamma-PGA as thickener, cryoprotectant, humectant, drug carrier, biological adhesive, flocculant, or heavy metal absorbent, etc. with biodegradability in the fields of food, cosmetics, medicine and water treatments are also reviewed.

Absorption↗
PubMed2006

Bio-based hydrogels prepared by cross-linking of microbial poly(gamma-glutamic acid) with various saccharides.

Novel bio-based hydrogels were prepared by cross-linking of microbial poly(gamma-glutamic acid) (PGA) with saccharides such as glucose, maltotriose, and cyclodextrin (CD) in the presence of water-soluble carbodiimide in dimethyl sulfoxide (DMSO) by one-pot synthesis at 25 degrees C for 24 h. The degradation of the gels in alkaline solution (pH 9) at 37 degrees C was also investigated. The PGA gels cross-linked with various neutral saccharides were obtained in relatively high recovery yields by use of a base like 4,4-(dimethylamino)pyridine. The PGA gel cross-linked by glucose showed the highest water absorption of 3000 g/g. The PGA gels cross-linked by CDs showed higher water absorption than those cross-linked by the corresponding linear saccharides. It was revealed that the water absorption of the PGA gel was affected by the cross-linker content and also the structure of cross-linkers as they had an effect on the cross-linking density of the PGA gel. The PGA gels were hydrolyzed under alkaline condition (pH 9) at 37 degrees C. The degradation rate was higher when the cross-linker content of the gel was lower.

Absorption↗