Glutamic acid and human intelligence.

"A review of the literature relating glutamic acid medication to the intellectual functioning of mental defectives indicates that positive effects tend to be reported in studies not employing a control group. The few positive studies employing controls contain methodological flaws, rendering their conclusions difficult to accept. The tendency for negative findings to occur in the more adequately designed experiments sheds doubt on the hypothesis that glutamic acid medication has a specifically beneficial effect on intellectual functioning." (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Glutamic acid decarboxylase and other autoantigens in IDDM

Most family policy implicitly or explicitly focuses on families with young children, but the revolution in longevity suggests the value of a life course focus, aimed at promoting the effectiveness of families and individuals at all ages and stages. Gerontologists can make a contribution by documenting and describing the gaps between needs and resources of families at all life stages, developing family indicators of social change, and sensitizing both decision makers and the public to the unintended consequences of existing or proposed policies.     

Analysis of antigen receptor genes in Hodgkin''s disease

We report three cases of fundic gland polyposis in the stomach identified in three patients who were related. Grossly the numerous polyps covered an area limited to the body and fundus of the stomach, no polyps were found in the antrum, duodenum, colon, or rectum, and histologically, the gastric lesions consisted of numerous hamartomatous polyps, characterized by proliferation of the fundic and cystic glands. The gastric lesions were identified in families without polyposis coli. This type of fundic gland polyposis has never been documented before in the literature.     

Double-stranded deoxyribonucleic acid binds to HLA class II molecules and inhibits HLA class II-mediated antigen presentation

CD4+ T cells proliferating in response to purified double-stranded deoxyribonucleic acid (dsDNA) have been recently demonstrated in peripheral blood mononuclear cells of patients with systemic lupus erythematosus. Their activation was inhibited by anti-HLA class II (HLA-II) monoclonal antibodies; thus, the existence of a molecular interaction between dsDNA and HLA-II is conceivable. In this report we show that dsDNA specifically bind to HLA-II. After preincubating cells with purified dsDNA or synthetic oligonucleotides, dsDNA was detected on the cell membrane and in the lysates of HLA-II+ but not of isogenic HLA-II- cell lines. We demonstrate that dsDNA binding inhibits that of a specific peptide to HLA-II. Mixed lymphocyte reaction and antigen-specific T cell proliferation were inhibited by the preincubation of stimulator cells or antigen-presenting cells with dsDNA. These results suggest the existence of a novel mechanism of down-modulation of the CD4+ T cell function generated by lack of stimulation due to the HLA-II presenting molecules being "occupied" by dsDNA.     

Determinants of tPA antigen and associations with coronary artery disease and acute cerebrovascular disease

A serum-free organ culture model for chondrocyte maturation, using the Avian sternum, was developed. Day-14 chick embryo sterna were placed in organ culture in the presence of defined medium. The optimal medium for chondrocyte terminal differentiation contained specific concentrations of dexamethasone, insulin, thyroid hormone and ascorbic acid. Three parameters, including sternal growth, cell diameter and type X collagen production, were analyzed as indicators of chondrocyte terminal differentiation. These parameters were analyzed in cephalic, middle and caudal regions of the organ-cultured chick sterna and compared to sterna grown in ovo. This study demonstrates that the organ-cultured tissue maintains normal morphological characteristics and terminal differentiation in the cephalic region only, similar to in ovo development, while maintaining normal cell-matrix relationships.     

Presence of IgM antibodies to Trypanosoma cruzi urinary antigen in sera from patients with acute Chagas'' disease

We have investigated the ability of an antisense immunoglobulin E (IgE) receptor alpha-subunit oligodeoxynucleotide (Fc epsilon RI alpha ODN) specifically to inhibit IgE-mediated allergic reactions in the mouse. Synthetic antisense Fc epsilon RI alpha ODN dose-dependently inhibited passive cutaneous anaphylaxis and histamine release from the mouse peritoneal mast cells (MPMC) activated by anti-dinitrophenyl (DNP) IgE. Northern blot analysis showed that the mast cells treated with antisense Fc epsilon RI alpha ODN exhibited no detectable levels of L-histidine decarboxylase mRNA after anti-DNP IgE stimulation, whereas the cells treated with sense Fc epsilon RI alpha ODN possessed significant amounts of this mRNA. Examination of the elevation of cAMP levels in MPMC following the activation with anti-DNP IgE demonstrated a significant rise in activated cells, but not in the antisense Fc epsilon RI alpha ODN-treated cells. Moreover, antisense Fc epsilon RI alpha ODN had a significant inhibitory effect on anti-DNP IgE-induced tumour necrosis factor-alpha production. Our results demonstrated that antisense Fc epsilon RI alpha ODN inhibited the IgE-mediated allergic reaction in vivo and in vitro.     

Concentration of endogenous tPA antigen in coronary artery disease: relation to thrombotic events, aspirin treatment, hyperlipidemia, and multivessel disease

Tissue plasminogen activator (tPA) is the major plasminogen activator responsible for dissolving blood clots found in blood vessels. However, elevated concentrations of tPA antigen were found to be related to adverse events in patients with coronary artery disease (CAD). Considerable controversy about the significance of these results exists. The goal of this cross-sectional study was to identify independent determinants for tPA antigen concentrations in patients with CAD, to possibly clarify the above paradoxical relationship. The baseline tPA antigen concentrations of 366 patients with angiographic evidence of coronary sclerosis were determined. Univariate analysis showed that age (P=0.013), angiographic extent of disease (P<0.001), presence of angina at rest (P<0.001), diabetes mellitus (P=0.004), hypercholesterolemia (P=0. 045), hypertriglyceridemia (P=0.015), and chronic intake of nitrates (P<0.001) were significantly and positively related to tPA antigen concentration, while the chronic intake of aspirin was inversely related to tPA antigen (P<0.001). In addition, plasminogen activator inhibitor type 1 (PAI-1) activity was found to be significantly and positively associated with tPA antigen concentration (P<0.001). A multivariate analysis identified chronic low-dose aspirin therapy (P<0.001), PAI-1 activity (P<0.001), hypertriglyceridemia (P=0.005), the type of angina (P=0.026), multivessel disease (P=0.041), and hypercholesterolemia (P=0.043) as significant and independent determinants of tPA antigen. While hypertriglyceridemia and hypercholesterolemia both are related to the underlying disease, the type of angina and the number of involved vessels are linked to the severity and extent of disease, and all of them are indicators of a prothrombotic state found during the progression of CAD. In contrary, low-dose aspirin rather would decrease the likelihood of thrombotic events. The relation of tPA antigen to PAI-1 activity furthermore underlines the relation between tPA antigen concentration and a prothrombotic state. Therefore, the positive or-in case of aspirin therapy-negative correlation of these parameters with tPA antigen concentration would indicate that thrombus formation and simultaneous endothelial cell activation might be major determinants for tPA antigen concentration in CAD.     

Glutamic acid 203 of the cAMP-dependent protein kinase catalytic subunit participates in the inhibition by two isoforms of the protein kinase inhibitor

Although the protein kinase inhibitors (PKIs) are known to be potent and specific inhibitors of the catalytic (C) subunit of cAMP-dependent protein kinase, little is known about their physiological roles. Glutamate 203 of the C alpha isoform (C alpha E203) has been implicated in the binding of the arginine 15 residue of the skeletal isoform of PKI (PKI alpha R15) (Knighton, D. R., Zheng, J., Ten Eyck, L. F., Xuong, N., Taylor, S.S., and Sowadski, J. M. (1991) Science 253, 414-420). To investigate the role of C alpha E203 in the binding of PKI and in vivo C-PKI interactions, in vitro mutagenesis was used to change the C alpha E203 codon of the murine C alpha cDNA to alanine and glutamine codons. Initially, the C alpha E203 mutant proteins were expressed and purified from Escherichia coli. C alpha E203 is not essential for catalysis as all of the C subunit mutants were enzymatically active. The mutation of Glu203 did increase the apparent Km for Leu-Arg-Arg-Ala-Ser-Leu-Gly (Kemptide) severalfold but did not affect the apparent Km for ATP. The Vmax(app) was not affected by the mutation of C alpha E203. The mutation of C alpha E203 compromised the ability of PKI alpha (5-24), PKI alpha, and PKI beta to inhibit phosphotransferase activity. PKI alpha was altered using in vitro mutagenesis to probe the role of Arg15 in interacting with C alpha E203. The PKI alpha R15A mutant was reduced in its inhibition of C alpha. Preliminary studies of the expression of these C alpha mutants in COS cells gave similar results. These results suggest that the C alpha E203 mutants may be useful in assessing the role of PKI in vivo.     

Increased vulnerability to 3-nitropropionic acid in an animal model of Huntington's disease

There is substantial evidence for both metabolic dysfunction and oxidative damage in Huntington's disease (HD). In the present study, we used in vivo microdialysis to measure the conversion of 4-hydroxybenzoic acid to 3,4-dihydroxybenzoic acid (3,4-DHBA) as a measure of hydroxyl radical production in a transgenic mouse model of HD, as well as in littermate controls. The conversion of 4-hydroxybenzoic acid to 3,4-DHBA was unchanged in the striatum of transgenic HD mice at baseline. Following administration of the mitochondrial toxin 3-nitropropionic acid (3-NP), there were significant increases in 3,4-DHBA generation in both control and transgenic HD mice, and the increases in the transgenic HD mice were significantly greater than those in controls. Furthermore, administration of 3-NP produced significantly larger striatal lesions in transgenic HD mice than in littermate controls. The present results show increased sensitivity to the mitochondrial toxin 3-NP in transgenic HD mice, which suggests metabolic dysfunction in this mouse model of HD.     

Carcinoembryonic antigen and immunoglobulin IgE in duodenal ulcer disease in children

The aim of this study was to monitor the behaviour of carcinoembryonic antigen (CEA) and immunoglobulin IgE level in children with duodenal ulcer disease. No sex-dependent differences were found in mean values of CEA, whereas the mean IgE level in boys was twice as high as in girls. No seasonal differences in CEA and IgE levels were found. The IgE concentration increased during exacerbations, and this difference was statistically significant. CEA levels changed according to a similar pattern during exacerbation and remission, but remained within normal limits.     

FVIII coagulant activity and antigen in subjects with ischaemic heart disease

A commercial IgM immunoblot kit was evaluated for dengue diagnosis with a panel of serum specimens collected from patients in a dengue endemic area. The kit is not recommended for use in its present form because of its undesirable rate of false-positive results. However, by substituting internal controls with the reference positive and negative controls that are more representative of those seen in endemic areas and by modifying the positive and negative scoring criteria, sensitivity and specificity of 80.3% and 94.5%, respectively, were obtained. These results are comparable with those obtained with the IgM ELISA on specimens, most of which were obtained from outpatient health care facilities. With further technical modifications, inclusion of a visual guide to ensure scoring standardization, and a more complete elaboration of the limitations of the test, wide application of the kit in diagnostic laboratories should be possible.     

A study of sialylated carbohydrate antigen in patients with benign bronchopulmonary disease

We studied the levels of carbohydrate antigen (CA 19-9, SLX, CA 50, Span-1, and Dupan-2) in serum, bronchoalveolar lavage fluid, and tissue from patients with benign bronchopulmonary disease. Patients had bronchiectasis, healed pulmonary tuberculosis, pulmonary fibrosis, or other diseases. Bronchoalveolar lavage fluid levels and immunohistochemical findings for lung tissue samples, in the absence of digestive and other diseases, suggested that elevated serum sialylated Lewis(A) (CA 19-9, CA 50, and Span-1) and Lewis(X) (SLX) antigen in patients with benign broncho-pulmonary disease are due to marked production of sialylated carbohydrate antigen in respiratory bronchioles. Common features of patients with benign bronchopulmonary disease include elevated serum carbohydrate antigen levels and bronchiectasis.     

Allograft coronary disease: the role of antigen independent mechanisms in pathogenesis

On seven dairy farms an attempt was made to control lungworm disease in calves by turnout on a pasture grazed earlier by cows, followed by a move to aftermath and ivermectin treatment 2 months later. Transmission of lungworm was observed on all farms. Lungworm disease occurred on four farms at treatment. Coughing re-occurred on three of these farms in some animals 2 months later. Owing to poor performance between turnout and treatment, weight gain was below the norm on the farm with the highest infections and most severe respiratory signs. On the other farms respiratory signs did not result in poor weight gain. Gastrointestinal nematode infections remained low on all farms. The conclusion is that this dose and move scheme cannot be recommended for the control of lungworm.     

Hepatobiliary clearance of glycocholic acid in Gilbert's disease

AIM: To research the behaviour of one biliary acid (glyco-cholic) i.v. injected in patients with Gilbert's disease and in healthy controls, so that contribute to the knowledge of the pathophysiological correlate between bilirubin and biliary acids. PATIENTS AND METHODS: We include 15 patients with Gilbert's disease and 7 healthy voluntary ones. We injected i.v. glycocholic acid and obtained the clearance curve (CG-RIA Abbot method). We evaluated the possible biostatistically significant differences between the obtained values of both groups though the non-parametric method of Mann-Whitney. RESULTS: The clearance curve of both groups had a similar profile; biostatisticaly there are not significant differences between the serum values of glyco-cholic acid in both groups. CONCLUSIONS: The clearance of the glyco-cholic acid in patients with Gilbert's disease had a similar behaviour as in healthy controls, without biostatisticaly significant differences between both groups.