Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antibodies were raised against synthetic peptides corresponding to several regions of the rat brain gamma-aminobutyric acid (GABA) transporter. According to our model, this glycoprotein has 12 transmembrane alpha-helices with both amino and carboxyl termini located in the cytoplasm. The antibodies recognized the intact transporter on Western blots. Upon papain treatment, a reconstitutively active transporter can be isolated upon lectin chromatography (Kanner, B. I., Keynan, S., and Radian, R. (1989) Biochemistry 28, 3722-3728). The papainized transporter runs on sodium dodecyl sulfate-polyacrylamide gels as a broad band with an apparent molecular mass between about 58 and 68 kDa as compared to 80 kDa for the untreated transporter. The transporter fragment was recognized by all the antibodies, except for that raised against the amino terminus. Pronase cleaves the transporter to a relatively sharp 60-kDa band, which reacts with the antibodies against the internal loops but not with either the amino- or the carboxyl-terminal. This pronase-treated transporter, upon isolation by lectin chromatography, was reconstituted. It exhibits full GABA transport activity. This activity exhibits the same features as the intact system including an absolute dependence on sodium and chloride as well as electrogenicity. We conclude that the amino- and carboxyl-terminal parts of the transporter, possibly including transmembrane alpha-helices 1, 2, and 12, are not required for the transport function.
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PMID:Neither amino nor carboxyl termini are required for function of the sodium- and chloride-coupled gamma-aminobutyric acid transporter from rat brain. 173 54

The bovine heart F0F1-ATPase preparation (Serrano, R., Kanner, B., and Racker, E. (1976) J. Biol. Chem. 251, 2453-2461) has been further delipidated. The lipid-deficient preparation contained 2.5 mol of cardiolipin, 1 mol of phosphatidylcholine (PC), and 1 mol of phosphatidylethanolamine (PE) per mol of F0F1. When reconstituted with asolectin the delipidated preparation exhibited an activity of 13 mumol of ATP hydrolyzed/min/mg of protein which was 88% oligomycin-sensitive. The phospholipids in this preparation were analyzed by 31P NMR spectroscopy to determine if they were immobilized by the enzyme (rendered NMR-invisible). The PC and PE were below the limits of detection under the conditions utilized and the cardiolipin was NMR-invisible until the enzyme was denatured by addition of either 1% sodium dodecyl sulfate or 8 M urea. Addition of cardiolipin to the delipidated preparation and subsequent analysis by NMR spectroscopy revealed that approximately 4 mol of cardiolipin were immobilized per mol of F0F1 ATPase. The enzyme appears to have high affinity for cardiolipin exclusively, since PC (a prominent inner membrane lipid), phosphatidyl serine (an acidic phospholipid), and phosphatidyl glycerol (the precursor to cardiolipin) were not immobilized (rendered NMR-invisible) when added to the delipidated preparation.
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PMID:Tightly associated cardiolipin in the bovine heart mitochondrial ATP synthase as analyzed by 31P nuclear magnetic resonance spectroscopy. 214 80

Plasma levels of testosterone and the adrenal androgen dehydroepiandrosterone sulfate (DHEA-S) were measured in male autistic subjects (31 prepubertal, 8 postpubertal), mentally retarded/cognitively impaired subjects (MR, 12 prepubertal), and normal control subjects (NC, 10 prepubertal, 11 postpubertal). Mean levels of plasma testosterone were similar in the postpubertal autistic (4.54 +/- 1.12 ng/ml) and postpubertal NC (5.02 +/- 1.87 ng/ml) groups. Plasma DHEA-S levels in postpubertal autistic (2170 +/- 1020 ng/ml) and postpubertal NC (1850 +/- 777 ng/ml) groups also were not significantly different. Similarly, no significant group differences were seen for testosterone or DHEA-S in the prepubertal autistic, MR, or NC individuals, although prepubertal MR individuals with cerebral palsy did have increased plasma DHEA-S levels compared to age-matched MR or NC individuals. Significant negative correlations were found between testosterone and whole blood serotonin (5-HT) levels in the combined (all subjects, all ages) groups and in the autistic group, suggesting that the effect of puberty on whole blood 5-HT may deserve further study. Data indicate that altered secretion of the androgens is not a common feature of autism. However, abnormalities of adrenal androgen secretion may be present in individuals with cerebral palsy.
J Autism Dev Disord 1995 Jun
PMID:Plasma androgens in autism. 755 94

Proper bodily response to environmental toxicants presumably requires proper function of the xenobiotic (foreign chemical) detoxification pathways. Links between phenotypic variations in xenobiotic metabolism and adverse environmental response have long been sought. Metabolism of the drug S-carboxymethyl-L-cysteine (SCMC) is polymorphous in the population, having a bimodal distribution of metabolites, 2.5% of the general population are thought to be nonmetabolizers. The researchers developing this data feel this implies a polymorphism in sulfoxidation of the amino acid cysteine to sulfate. While this interpretation is somewhat controversial, these metabolic differences reflected may have significant effects. Additionally, a significant number of individuals with environmental intolerance or chronic disease have impaired sulfation of phenolic xenobiotics. This impairment is demonstrated with the probe drug acetaminophen and is presumably due to starvation of the sulfotransferases for sulfate substrate. Reduced metabolism of SCMC has been found with increased frequency in individuals with several degenerative neurological and immunological conditions and drug intolerances, including Alzheimer's disease, Parkinson's disease, motor neuron disease, rheumatoid arthritis, and delayed food sensitivity. Impaired sulfation has been found in many of these conditions, and preliminary data suggests that it may be important in multiple chemical sensitivities and diet responsive autism. In addition, impaired sulfation may be relevant to intolerance of phenol, tyramine, and phenylic food constituents, and it may be a factor in the success of the Feingold diet. These studies indicate the need for the development of genetic and functional tests of xenobiotic metabolism as tools for further research in epidemiology and risk assessment.
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PMID:Phenotypic variation in xenobiotic metabolism and adverse environmental response: focus on sulfur-dependent detoxification pathways. 871 48

Two boys from separate families presented with hereditary multiple exostoses (EXT) and autism associated with mental retardation. Their fathers both expressed a clinical phenotype of hereditary multiple exostoses milder than those of the patients and without the associated mental disorder. The EXT1 and EXT2 genes from lymphocytes of the affected individuals were analyzed by using denaturing high-performance liquid chromatography and direct sequencing. A novel deletion mutation, 1742delTGT-G in exon 9 of EXT1, causing a frameshift was detected in one boy and his father. Another novel deletion mutation, 2093delTT in exon 11 of EXT1, causing transcription termination was detected in the other affected boy and his father. EXT1 is expressed in the brain, and both EXT1 and EXT2 proteins are associated with glycosyltransferase activities required for the biosynthesis of heparan sulfate, which also has activity in the brain. The coincidental association of mental disorders in the boys was not completely excluded. However, these results suggest the involvement of EXT1 in the development of mental disorders, including mental retardation and autism.
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PMID:Association of autism in two patients with hereditary multiple exostoses caused by novel deletion mutations of EXT1. 1203 95

We measured autoantibodies against nine different neuron-specific antigens and three cross-reactive peptides in the sera of autistic subjects and healthy controls by means of enzyme-linked immunosorbent assay (ELISA) testing. The antigens were myelin basic protein (MBP), myelin-associated glycoprotein (MAG), ganglioside (GM1), sulfatide (SULF), chondroitin sulfate (CONSO4), myelin oligodendrocyte glycoprotein (MOG), alpha,beta-crystallin (alpha,beta-CRYS), neurofilament proteins (NAFP), tubulin and three cross-reactive peptides, Chlamydia pneumoniae (CPP), streptococcal M protein (STM6P) and milk butyrophilin (BTN). Autistic children showed the highest levels of IgG, IgM and IgA antibodies against all neurologic antigens as well as the three cross-reactive peptides. These antibodies are specific because immune absorption demonstrated that only neuron-specific antigens or their cross-reactive epitopes could significantly reduce antibody levels. These antibodies may have been synthesized as a result of an alteration in the blood-brain barrier. This barrier promotes access of preexisting T-cells and central nervous system antigens to immunocompetent cells, which may start a vicious cycle. These results suggest a mechanism by which bacterial infections and milk antigens may modulate autoimmune responses in autism.
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PMID:Antibodies to neuron-specific antigens in children with autism: possible cross-reaction with encephalitogenic proteins from milk, Chlamydia pneumoniae and Streptococcus group A. 1216 Oct 33

The cyclic adenosine monophosphate-specific phosphodiesterase-4 (PDE4) gene family is the target of several potential therapeutic inhibitors and the PDE4B gene has been associated with schizophrenia and depression. Little, however, is known of any connection between this gene family and autism, with limited effective treatment being available for autism. We measured the expression of PDE4A and PDE4B by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting in Brodmann's area 40 (BA40, parietal cortex), BA9 (superior frontal cortex), and cerebellum from subjects with autism and matched controls. We observed a lower expression of PDE4A5, PDE4B1, PDE4B3, PDE4B4, and PDE4B2 in the cerebella of subjects with autism when compared with matched controls. In BA9, we observed the opposite: a higher expression of PDE4AX, PDE4A1, and PDE4B2 in subjects with autism. No changes were observed in BA40. Our results demonstrate altered expressions of the PDE4A and PDE4B proteins in the brains of subjects with autism and might provide new therapeutic avenues for the treatment of this debilitating disorder.
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PMID:Expression of phosphodiesterase 4 is altered in the brains of subjects with autism. 1809 Mar 23

The goal of this study was to evaluate transsulfuration metabolites in participants diagnosed with autism spectrum disorders (ASDs). Transsulfuration metabolites, including: plasma reduced glutathione (GSH), plasma oxidized glutathione (GSSG), plasma cysteine, plasma taurine, plasma sulfate, and plasma free sulfate among participants diagnosed with ASDs (n = 38) in comparison to age-matched neurotypical controls were prospectively evaluated. Testing was conducted using Vitamin Diagnostics, Inc. (CLIA-approved). Participants diagnosed with ASDs had significantly (P < 0.001) decreased plasma reduced GSH, plasma cysteine, plasma taurine, plasma sulfate, and plasma free sulfate relative to controls. By contrast, participants diagnosed with ASDs had significantly (P < 0.001) increased plasma GSSG relative to controls. The present observations are compatible with increased oxidative stress and a decreased detoxification capacity, particularly of mercury, in patients diagnosed with ASDs. Patients diagnosed with ASDs should be routinely tested to evaluate transsulfuration metabolites, and potential treatment protocols should be evaluated to potentially correct the transsulfuration abnormalities observed.
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PMID:A prospective study of transsulfuration biomarkers in autistic disorders. 1861 12

Autism spectrum disorders (ASDs) may result from a combination of genetic/biochemical susceptibilities in the form of a reduced ability to excrete mercury and/or increased environmental exposure at key developmental times. Urinary porphyrins and transsulfuration metabolites in participants diagnosed with an ASD were examined. A prospective, blinded study was undertaken to evaluate a cohort of 28 participants with an ASD diagnosis for Childhood Autism Rating Scale (CARS) scores, urinary porphyrins, and transsulfuration metabolites. Testing was conducted using Vitamin Diagnostics, Inc. (CLIA-approved) and Laboratoire Philippe Auguste (ISO-approved). Participants with severe ASDs had significantly increased mercury intoxication-associated urinary porphyrins (pentacarboxyporphyrin, precoproporphyrin, and coproporphyrin) in comparison to participants with mild ASDs, whereas other urinary porphyrins were similar in both groups. Significantly decreased plasma levels of reduced glutathione (GSH), cysteine, and sulfate were observed among study participants relative to controls. In contrast, study participants had significantly increased plasma oxidized glutathione (GSSG) relative to controls. Mercury intoxication-associated urinary porphyrins were significantly correlated with increasing CARS scores and GSSG levels, whereas other urinary porphyrins did not show these relationships. The urinary porphyrin and CARS score correlations observed among study participants suggest that mercury intoxication is significantly associated with autistic symptoms. The transsulfuration abnormalities observed among study participants indicate that mercury intoxication was associated with increased oxidative stress and decreased detoxification capacity.
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PMID:Biomarkers of environmental toxicity and susceptibility in autism. 1926 2

Molecular and behavioural evidence points to an association between sex-steroid hormones and autism spectrum conditions (ASC) and/or autistic traits. Prenatal androgen levels are associated with autistic traits, and several genes involved in steroidogenesis are associated with autism, Asperger Syndrome and/or autistic traits. Furthermore, higher rates of androgen-related conditions (such as Polycystic Ovary Syndrome, hirsutism, acne and hormone-related cancers) are reported in women with autism spectrum conditions. A key question therefore is if serum levels of gonadal and adrenal sex-steroids (particularly testosterone, estradiol, dehydroepiandrosterone sulfate and androstenedione) are elevated in individuals with ASC. This was tested in a total sample of n=166 participants. The final eligible sample for hormone analysis comprised n=128 participants, n=58 of whom had a diagnosis of Asperger Syndrome or high functioning autism (33 males and 25 females) and n=70 of whom were age- and IQ-matched typical controls (39 males and 31 females). ASC diagnosis (without any interaction with sex) strongly predicted androstenedione levels (p<0.01), and serum androstenedione levels were significantly elevated in the ASC group (Mann-Whitney W=2677, p=0.002), a result confirmed by permutation testing in females (permutation-corrected p=0.02). This result is discussed in terms of androstenedione being the immediate precursor of, and being converted into, testosterone, dihydrotestosterone, or estrogens in hormone-sensitive tissues and organs.
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PMID:Increased serum androstenedione in adults with autism spectrum conditions. 2139 41


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