Childhood Type 1 diabetes and parental occupation involving parental mixing and infectious contacts.
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Biomedical subjects
Publications and source records attributed to J Evans.
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We reviewed 13 cases of ultrasound-guided thrombin injection of femoral pseudoaneurysms. All cases occurred within a 17-month period from January 1998 through May 1999 and were complications of femoral artery puncture. Immediate total thrombosis occurred in nine of 13 patients. Twenty-four-hour follow-up ultrasound in seven patients revealed no recurrence of pseudoaneurysm. Two of 13 patients required operative repair. One pseudoaneurysm thrombosed with 15 minutes of compression after injection and one case required a second injection. No cases of arterial thrombosis were noted. Ultrasound-guided thrombin injection for femoral artery pseudoaneurysm represents a safe and effective alternative to operative repair.
Two forms of glycine transporter have been described to date, GlyT-1 and GlyT-2. The GlyT-2 form is expressed mainly in the spinal cord, brainstem and cerebellum. Here we describe the identification of a variant form of the human GlyT-2 (SC6), showing three amino acid changes to the previously reported protein. Population analysis identified the allele causing one of the polymorphisms, D463N, at 10% within the population with 3% being homozygous for the change. We also transfected our new variant into mammalian cells and compared it to the published cDNA, showing that the three amino acid changes present have no major effect on the biochemical properties of the transporter.
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Motilin is a 22-amino acid peptide hormone expressed throughout the gastrointestinal (GI) tract of humans and other species. It affects gastric motility by stimulating interdigestive antrum and duodenal contractions. A heterotrimeric guanosine triphosphate-binding protein (G protein)-coupled receptor for motilin was isolated from human stomach, and its amino acid sequence was found to be 52 percent identical to the human receptor for growth hormone secretagogues. The macrolide antibiotic erythromycin also interacted with the cloned motilin receptor, providing a molecular basis for its effects on the human GI tract. The motilin receptor is expressed in enteric neurons of the human duodenum and colon. Development of motilin receptor agonists and antagonists may be useful in the treatment of multiple disorders of GI motility.
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Query of the expressed sequence tag database with the rat metabotropic GABABR1A receptor amino acid sequence using the TFASTA algorithm revealed two partial cDNA fragments whose sequence information was then used to isolate by PCR a novel full-length human cDNA encoding a putative G-protein-coupled receptor (GPCR), termed GPR 51. Sequence analysis revealed that it encoded a protein of 941 amino acids, similar in size and homology to GABAB receptors followed by metabotropic glutamate receptors but not other GPCRs. GPR 51 expressed in COS-1 cells showed no specific binding for [3H](+)baclofen and when expressed in Xenopus oocyte and Xenopus melanophore functional assays showed no activity to GABA, (-)baclofen, and glutamic acid. Northern blot analysis and in situ hybridization revealed that GPR 51 transcripts were predominantly expressed in the central nervous system with highest abundance in the cortex, thalamus, hippocampus, amygdala, cerebellum, and spinal cord. In contrast, GPR 51 receptor transcripts were almost not detected in the peripheral tissues. Gene GPR 51 was localized by radiation hybrid mapping to chromosome 9, 4.81 cR from the WI-8684 marker, and proximal to the hereditary sensory neuropathy type 1 locus.
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Expression of protein kinase C (PKC) isoenzymes -alpha, -beta, -delta, -epsilon, -gamma, -iota, -lambda, -mu, -theta, and -zeta, and of their common receptor for activated C-kinase (RACK)-1, was determined immunohistochemically using specific antibodies in formalin-fixed and paraffin-embedded specimens of early prostatic adenocarcinomas (n = 23) obtained at radical prostatectomy. Expression of each isoenzyme by malignant tissues was compared with nonneoplastic prostate tissues removed at radical cystectomy (n = 10). The most significant findings were decreased PKC-beta expression in early neoplasia when compared to benign epithelium (P < 0.0001), together with a reciprocal increase in expression of PKC-epsilon (P < 0.0001). Detectable levels of PKC-alpha and PKC-zeta were also significantly increased in the cancers (P = 0.045 and P = 0.015 respectively) but did not correlate with either PKC-beta or PKC-epsilon for individual cases. Alterations in the levels of the four PKC isoenzymes occurred specifically and consistently during the genesis and progression of human prostate cancer. PKC-delta, -gamma, and -theta were not expressed in the epithelium of either the benign prostates or the cancers. Levels of expression for PKC-A, -iota, -mu, and RACK-1 were not significantly different between the benign and malignant groups. Although changes in PKC isoenzyme expression may assist in explaining an altered balance between proliferation and apoptosis, it is likely that changes in activity or concentrations of these isoenzymes exert important modulating influences on particular pathways regulating cellular homeostasis. The findings of this study raise an exciting possibility of novel therapeutic intervention to regulate homeostatic mechanisms controlling proliferation and/or apoptosis, including expression of the p170 drug-resistance glycoprotein, intracellular Ca2+ concentrations, and enhanced cellular mobility resulting in the metastatic dissemination of human prostate cancer cells. Attenuation of PKC-beta expression is currently being assessed as a reliable objective adjunct to morphological appearance for the diagnosis of early progressive neoplasia in human prostatic tissues.
Venoms of the broad-banded copperhead (Agkistrodon contortrix laticinctus, ACL) and the prairie rattlesnake (Crotalus viridis viridis, CVV), like other crotalid venoms, cause severe local tissue damage such as edema, hemorrhage and myonecrosis. Antivenom therapy is not very effective in neutralizing this local tissue damage, and such observations support the need for an effective first-aid regimen aimed at minimizing local tissue reactions. Some of the local tissue damage induced by these venoms is due to phospholipase A2 myotoxins, and since para-bromophenacyl bromide (p-BPB), an inhibitor of PLA2 catalytic activity, has been shown to inhibit the myotoxic action of two PLA2 myotoxins, we hypothesized that this compound would inhibit part of the myotoxic activity of these crude venoms. For in vitro neutralization experiments, venoms were mixed with combinations of either p-BPB, antivenom or both prior to injection into the muscles of the lower hindlimb of mice. For in vivo neutralization experiments, mice were injected with venom followed by either topical DMSO containing p-BPB or intramuscular injection with saline containing p-BPB. A final set of mice received these same injections followed by i.p. infusions of antivenom to simulate experimental first-aid followed by hospital treatment. In the in vitro neutralization tests, edema was significantly reduced when both antagonists were used together, and there was a highly significant neutralization of ACL- and CVV-generated myonecrosis. In the in vivo neutralization experiments, hemorrhage was significantly reduced when injection of ACL venom was followed by topical DMSO-p-BPB, and myonecrosis was reduced when injection of ACL venom was followed by intramuscular injection of saline-p-BPB. Antivenom significantly reduced edema, hemorrhage and myonecrosis induced by CVV venom, but reduced only myonecrosis induced by ACL venom. Taken together, these results suggest a role for pBPB in the first-aid treatment of snakebite especially when followed by hospital treatment with antivenom.
OBJECTIVE: Abnormalities in the mucosal lining of the vocal folds may interfere with the normal vibratory patterns and result in vocal limitations, especially for singers whose demands are great. A prospective, longitudinal study was undertaken to investigate the incidence of laryngeal abnormalities in asymptomatic singing students. METHODS: Sixty-five singing students at the school of music underwent videostroboscopic evaluation and completed a comprehensive questionnaire. Videos were rated by 3 experienced clinicians, and interrater reliability was calculated. Results were correlated with demographic factors, background medical history, and singing history. RESULTS: Five students (8.3%) exhibited early signs of benign vocal fold lesions (2 with nodules and 3 with cysts). A high incidence of posterior erythema (n = 44; 73.4%), suggesting possible reflux, was found. CONCLUSIONS: A surprisingly high number of otherwise asymptomatic singing students demonstrated abnormal laryngeal findings. Their relationship with vocal performance will be addressed as well as implications for preventative measures.
A radioiodinated probe, [125I]-CGP 71872, containing an azido group that can be photoactivated, was synthesized and used to characterize GABA(B) receptors. Photoaffinity labeling experiments using crude membranes prepared from rat brain revealed two predominant ligand binding species at approximately 130 and approximately 100 kDa believed to represent the long (GABA(B)R1a) and short (GABA(B)R1b) forms of the receptor. Indeed, these ligand binding proteins were immunoprecipitated using a GABA(B) receptor-specific antibody confirming the receptor specificity of the photoaffinity probe. Most convincingly, [125I]-CGP 71872 binding was competitively inhibited in a dose-dependent manner by cold CGP 71872, GABA, saclofen, (-)-baclofen, (+)-baclofen and (L)-glutamic acid with a rank order and stereospecificity characteristic of the GABA(B) receptor. Photoaffinity labeling experiments revealed that the recombinant GABA(B)R2 receptor does not bind [125I]-CGP 71872, providing surprising and direct evidence that CGP 71872 is a GABA(B)R1 selective antagonist. Photoaffinity labeling experiments using rat tissues showed that both GABA(B)R1a and GABA(B)R1b are co-expressed in the brain, spinal cord, stomach and testis, but only the short GABA(B)R1b receptor form was detected in kidney and liver whereas the long GABA(B)R1a form was selectively expressed in the adrenal gland, pituitary, spleen and prostate. We report herein the synthesis and biochemical characterization of the nanomolar affinity [125I]-CGP 71872 and CGP 71872 GABA(B)R1 ligands, and differential tissue expression of the long GABA(B)R1a and short GABA(B)R1b receptor forms in rat and dog.
The aim of the study was to identify the comorbidity of autistic spectrum disorders in a population of children with Down syndrome (DS). All children with DS within a defined population of South Birmingham were identified. The Asperger Syndrome Screening Questionnaire and the Child Autism Rating Scale were completed and diagnosis made according to ICD-10 criteria following interview and observation. Thirty-three of 58 identified children completed the measures, four of whom received a diagnosis of an autistic spectrum disorder. This is equivalent to a minimum comorbid rate of 7%. The questionnaire items concerning social withdrawal, restricted or repetitive interests, clumsiness, and unusual eye contact were associated with an autistic disorder. Of the remaining 29 participating children, 11 also displayed marked obsessional and ritualistic behaviours. The comorbid occurrence of autism and DS is at least 7%. It is important that these children are identified and receive appropriate education and support. A full assessment of social, language, and communication skills and behaviour is crucial, particularly in children with DS who appear different from other children with DS. Potential mechanisms accounting for this comorbidity are discussed.