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Biomedical subjects

C E Elliott

Publications and source records attributed to C E Elliott.

At least 19 recordsLinked to original sources
PubMed1997

Plectin transcript diversity: identification and tissue distribution of variants with distinct first coding exons and rodless isoforms.

Plectin is a widely expressed protein that is very large in size and that has all the attributes of a multifunctional crosslinking and organizing element of the cytoskeleton. It displays a multidomain structure, versatile binding activities, and subcellular localizations that enable it to strengthen cells against mechanical stress forces. Moreover, hereditary gene defects in plectin cause epidermolysis bullosa simplex (EBS)-MD, a severe skin blistering disease with muscular dystrophy. Here we report the analysis of the exonintron organization of the rat plectin gene and the identification of several different isoforms on the transcriptional level. We show that of 35 coding exons identified, 4 serve as alternative first exons splicing into the same successive exon 2, which is the first of 7 exons encoding a highly conserved actin-binding domain. RNase protection mapping of transcripts containing 3 of the identified 4 alternate first exons revealed their coexpression in rat glioma C6 cells and in a series of different rat tissues that we examined. Significant variations in expression levels of first exons indicated the possibility of tissue-specific promoter usage. In addition, plectin splice variants lacking exon 31 (> 3 kb), which encodes the entire rod domain of the molecule, were identified in a variety of rat tissues. This study provides first insights into a complex plectin gene regulatory machinery with similarities to that of dystrophin.

Alternative Splicing↗
PubMed1995

Maternal attachment status, psychosocial stressors and problem behaviour: follow-up after parent training courses for conduct disorder.

37 Mothers of children with conduct disorder who had received Parent Management Training (PMT) were interviewed using the Adult Attachment Interview, 13-43 months after treatment. Child behaviour levels at follow-up were strongly associated with the scores at referral in the unresolved attachment group, but not in the resolved group. This was reflected in a statistical interaction between referral behaviour score and resolved/unresolved attachment status in a regression model. This model, which also included a strong independent contribution from a composite psychological stress index, explained 66% of the variance in follow-up behaviour scores. The implications of these results for predicting the outcome of PMT are discussed.

Child↗
PubMed1995

Impact of functional severity on self concept in young people with spina bifida.

This study examines the relationship between medical and functional severity of disability and levels of self esteem and self concept in 79 young people with spina bifida. Greater feelings of global self worth and of self esteem in physical appearance were associated with greater severity of disability. This was only in part an effect of lower IQ among the most disabled young people. Many of the least disabled had marked impairment of self esteem. Analysis of the impact of individual aspects of disability confirmed the association between increased self esteem in physical appearance and global self worth, and diminished functional ability. Academic self ratings, however, were higher in the less disabled. Hydrocephalus and continence appeared to have minimal effect on self esteem. The relationship between severity of disability in spina bifida and self concept is complex and mediated by a range of factors. It is incorrect to assume that the psychological impact is less in the mildly disabled young person.

Adolescent↗
PubMed1995

Cloning, expression and pharmacological characterization of a human glutamate receptor: hGluR4.

A member of the ionotropic family of glutamate receptors, hGluR4, was isolated from a human cDNA library and characterized following expression in mammalian cell lines. Human GluR4 possessed a 99% amino acid and 92% nucleotide homology to that of its rat counterpart with sequence differences restricted to the carboxy and amino terminal regions of the molecule. Transfection of simian kidney cells (COS-1) with an hGluR4 expression plasmid resulted in the transient formation of a membrane protein that possessed high specific binding for [3H](RS)-alpha-amino- 3-hydroxy-5-methylisoxazole-4-propionic acid ([3H]AMPA) but not [3H]kainate. Competition studies yielded a displacement profile of AMPA = quisqualate > glutamate > domoate > kainate >> N-methyl-D-aspartate (NMDA) or dihydrokainate. Whole-cell, voltage-clamp recordings from a human embryonic kidney cell line (HEK 293) stably expressing hGluR4 confirmed the presence of constitutively active, ligand-gated ion channels activated by AMPA, glutamate and kainate but not N-methyl-D-aspartate. Kainate-evoked currents were reversibly attenuated by 6-cyano-7-nitro- quinoxaline-2,3-dione (CNQX) but not DL-2-amino-5- phosphonovalerate (DL-AP5). Agonist-evoked currents exhibited inward rectification and ion substitution experiments indicated that hGluR4 receptor-linked ion channels in their homomeric state are permeable to both CA2+ and Na+ ions. In the same cell line antibody to rat GluR4 immunoprecipitated a major protein band at approximately 108 kDa and a minor one at approximately 340 kDa. The immunoblot analysis of membranes chemically crosslinked with dithiobis(succinimidylpropionate) showed a broad band at 550-600 kDa suggesting that the GluR4 receptor forms a pentamer in situ. This is the first report of the cloning of hGluR4 receptor and its stable expression in a human cell line.

Amino Acid Sequence↗
PubMed1995

cDNA cloning and functional properties of human glutamate receptor EAA3 (GluR5) in homomeric and heteromeric configuration.

We have isolated a new member of the human glutamate receptor family from a fetal brain cDNA library. This cDNA clone, designated EAA3a, shares a 90% nucleotide identity with the previously reported rat GluR5-2b cDNA splice variant and differed from human GluR5-1d in the amino and carboxy terminal regions. Cell lines stably expressing EAA3a protein formed homomeric ligand-gated ion channels responsive, in order of decreasing affinity to domoate, kainate, L-glutamate and (RS)-alpha-amino-3-hydroxy-5- methylisoxazole-propionate (AMPA). Kainate-evoked currents showed partial desensitization that was reduced on incubation with concanavalin A (conA) but not cyclothiazide and were attenuated by the non-N-methyl-D-aspartate (NMDA) receptor antagonist CNQX (6-cyano-7-nitro-quinoxalinedione). Coexpression of EAA3a and human EAA1 cDNAs in HEK 293 cells formed a heteromeric channel with unique properties. Kainate and AMPA activated the heteromeric channel with significantly higher affinities than observed for EAA3a alone. Ligand binding studies with the recombinant EAA3a receptor expressed in mammalian cells indicated a high affinity kainate binding site (Kd = 120 +/- 15.0 nM). The relative potency of compounds in displacing [3H]-kainate binding to EAA3a receptor was: domoate > kainate > L-glutamate = quisqualate > 6,7-dinitroquinoxaline-2,3-dione (DNQX) = CNQX > AMPA > dihydrokainate > NMDA.

Amino Acid Sequence↗
PubMed1994

Human glutamate receptor hGluR3 flip and flop isoforms: cloning and sequencing of the cDNAs and primary structure of the proteins.

Several cDNA clones encoding the human glutamate receptor subunit GluR3 flip and flop isoforms, were isolated from human hippocampus and fetal brain libraries. DNA sequence analysis revealed overlapping clones permitting the reconstruction of full-length GluR3-flip and GluR3-flop cDNAs. The GluR3 cDNAs demonstrated an 94.1-94.7% nucleotide (nt) identity with the corresponding rat cDNAs. The nt sequence of the GluR3 cDNAs would encode 894 amino acid proteins that have a 99.4% identity with the rat GluR3 isoforms. The human GluR3 cDNAs predict an additional 6 amino acid in the N-terminal signal peptide as compared to the rat GluR3.

Alternative Splicing↗
PubMed1994

The self-concept of young people with spina bifida: a population-based study.

Seventy-nine young people with spina bifida were given a psychological, medical, carer and occupational therapy assessment. 79 matched able-bodied young people received the psychosocial interview. The disabled group felt themselves to be less competent in academic, athletic and social aspects of self-concept, less supported by classmates, equally supported by parents and friends and more supported by teachers than the able-bodied group. Disabled subjects did not discount the importance of any area of personal-social functioning, and experienced greater discrepancies between competence and importance in most academic, athletic, social and physical appearance aspects of self-concept. Disabled girls assigned very high importance to physical appearance. Physical appearance was more strongly associated with general self-esteem than any other area of self-concept.

Adolescent↗
PubMed1994

Functional expression and pharmacological characterization of the human EAA4 (GluR6) glutamate receptor: a kainate selective channel subunit.

A cDNA encoding an ionotropic glutamate receptor subunit protein humEAA4 (GluR6), has been cloned from a human fetal brain library. This cDNA when expressed in COS or HEK-293 cells is associated with high-affinity kainate receptor binding and ion channel formation. We have successfully established cell lines stably expressing humEAA4 in HEK-293 cells This is the first report of the establishment of stable cell lines expressing a glutamate receptor channel. The relative potency of compounds for displacing [3H]-kainate binding to humEAA4 receptors expressed in COS or HEK-293 cells is domoate > kainate > quisqualate > 6-cyano-7-nitroquinoxaline-2,3-dione > L-glutamate = 6,7- dinitroquinoxaline-2,3-dione > dihydrokainate. Applications of kainate, glutamate, and domoate but not AMPA evoked rapidly desensitizing currents in cells expressing homo-oligomeric humEAA4 in a concentration dependent manner. The order of potency was: domoate > kainate > L-glutamate. Although AMPA did not itself activate humEAA4 receptors it did reduce, to a limited extent, kainate-evoked responses. AMPA may therefore be a weak partial agonist for this receptor. To date this effect has not been demonstrated with rat GluR6. It is possible that subtle species differences may exist in the nature of agonist receptor interaction. Kainate evoked currents were attenuated by the quinoxalinediones CNQX and DNQX but not by DAP5. The receptor desensitization was attenuated on application of concanavalin A. Ion-permeability studies indicated that the receptor-linked ion channel is permeable to both Na+ and Ca2+ ions.

Amino Acid Sequence↗
PubMed1994

Molecular characterization of the human EAA5 (GluR7) receptor: a high-affinity kainate receptor with novel potential RNA editing sites.

Several cDNA clones encoding EAA5 receptor polypeptides were isolated from a human fetal brain library. The EAA5 cDNAs demonstrated an 88.7-90.1% nucleotide identity with rat GluR7 cDNAs. The nucleotide sequence of EAA5 would encode a 919-amino acid protein, that has a 97.7-98.9% identity with the rat GluR7 receptor. Two variation of the EAA5 cDNA were identified which result in amino acid substitutions in the predicted extracellular amino-terminal region; Ser310-->Ala and Arg352-->Gln. These variations can be attributed to RNA editing involving T-->G and G-->A substitutions. Both the location (with respect to glutamate receptors), and the nucleotides involved, in this putative RNA editing are novel and may therefore involve novel mechanisms. Ligand binding studies with membranes of transfected COS-1 cells expressing EAA5 polypeptides demonstrate a rank order of ligand affinity similar to that observed with the rat GluR7 receptor, and a dissociation constant for kainate (2.72 +/- 0.12 nM (n = 3)) that is approximately 20- to 30-fold higher than that observed for the rat GluR7 receptor. All of the ligands tested had a higher affinity for the human EAA5 receptor as compared to the rat GluR7 receptor. This report provides another example of pharmacological differences for similar receptors across species.

Amino Acid Sequence↗
PubMed1994

Acute renal failure in IgA nephropathy.

Twenty-five (3%) of 865 patients with IgA nephropathy presented with acute renal failure (ARF). These patients were matched with 25 patients in the same series who presented with irreversible renal impairment. Patients with acute renal failure had a significantly higher incidence of macroscopic hematuria and red blood cells in tubules. Conversely, a greater percentage of patients with irreversible renal failure had > or = 40% sclerosed glomeruli. The long-term prognosis for patients presenting with ARF appears excellent with only 1 (4%) patient developing chronic renal failure after a mean follow-up of 65 months. Mechanisms of acute renal failure in IgA nephropathy are discussed.

Acute Kidney Injury↗
PubMed1992

Obstetrics in a small maternity hospital.

This paper presents the case for continuing to practise safe obstetrics in a small suburban hospital. Boothville Maternity Hospital, Brisbane, is a Salvation Army hospital of 20 beds. Seven thousand births during the years 1975 to 1989 are reported. Perinatal mortality rate was 4.9/1000 total births, forceps rate 7.1%, caesarean rate 9.3% and transfer rate to larger centres 1.6% for babies and 1.2% for mothers. Personalised family-centred care in congenial surroundings serves to maximise the factors that favour uncomplicated delivery. Large centralised and small peripheral hospitals should be seen not as competitive but as complementary. Boothville provides mutually satisfying co-operation for care-givers and care-receivers.

Family↗
PubMed1991

Ten cases of acute lead intoxication among bridge workers in Louisiana.

We report the cases of ten construction workers who developed acute lead intoxication while repairing a bridge in Louisiana. All but one patient received a five-day course of edetate calcium disodium (calcium EDTA) chelation therapy; one patient received five doses instead of five days of treatment. Calcium EDTA 25 mg/kg q12h was administered for ten consecutive doses by intravenous infusion over two hours. Each dose was diluted in NaCl 0.9% 500 mL. No adverse drug effects were observed during treatment. The posttreatment mean whole blood lead (PbB) concentration was significantly reduced compared with the pretreatment mean PbB (1.48 +/- 0.70 vs. 3.8 +/- 1.68 mumol/L; p = 0.0012, Student's paired t-test). This indicates that the body lead burden of these patients was effectively reduced with calcium EDTA. Eight patients had complaints on admission that were suggestive of lead intoxication. These included malaise, numbness of the extremities, arthralgia, myalgia, abdominal discomfort, sleep disturbance, and lower back pain. Patients had no complaints on discharge. Eight patients had mild anemia that was consistent with acute lead intoxication (mean pretreatment hemoglobin (+/- SD), 128.6(+/- 17.2 g/L), but calcium EDTA therapy did not appear to effect any change in the pretreatment hemoglobin values. The Occupational Safety and Health Administration (OSHA) lead standard requires that manufacturers provide employees at risk for occupational lead exposures with proper respirators and medical surveillance to prevent lead intoxication. The construction industry is exempted from these standards except in Maryland. We believe that amendment of the OSHA lead standards, to provide specific lead regulation of the construction industry, would be helpful in preventing similar cases of occupational lead intoxication.

Acute Disease↗
PubMed1985

Studies on the effect of chronic consumption of moderate amounts of ethanol on male rat hepatic microsomal drug-metabolizing activity.

Weanling, male Sprague-Dawley rats given 10% ethanol in the drinking water and food ad lib. for up to 8 weeks consumed 17% of their calories as ethanol. The alanine aminotransferase (ALT), aspartate aminotransferase (AST), and liver histology by light microscopy were unaffected by this treatment. Similarly, hepatic microsomal NADPH-cytochrome c reductase, ethylmorphine N-demethylase and benzphetamine N-demethylase activities were also not affected by ethanol consumption. On the other hand, cytochrome P-450 content, aniline hydroxylase activity and acetaminophen metabolism as measured by both the cysteine conjugate and the [3H]acetaminophen covalently-bound to microsomal protein were increased significantly by ethanol consumption. The maximal effect was seen by 6 weeks. The 2- to 3-fold increase in aniline and acetaminophen metabolism, the absence of liver damage, and the similarity in weight gains and caloric intakes for controls and treated animals suggest that the rat on 10% ethanol in the drinking water is a reasonable model for studies of the effect of moderate alcohol consumption on specific biochemical pathways.

Acetaminophen↗