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991.
Michael Rosenzweig Martha Skinner Tatiana Prokaeva Roger Théberge Catherine Costello Brian M Drachman Lawreen H Connors 《Amyloid》2007,14(1):65-71
We report the identification of a new transthyretin (TTR) gene mutation and variant protein, Glu61Gly, in a 55-year-old man with progressive cardiomyopathy, mild peripheral neuropathy and bilateral carpal tunnel syndrome. A diagnosis of TTR-associated familial amyloidosis (ATTR) was considered after an endomyocardial biopsy revealed amyloid deposits in the heart of a patient who had no family history of amyloidosis and no evidence of a plasma cell dyscrasia. Serum screening for a TTR variant by isoelectric focusing (IEF) was positive and prompted further studies to identify the genetic abnormality and to characterize the amyloidogenic protein. Direct DNA sequence analysis of all four coding regions in the TTR gene demonstrated heterozygosity in exon 3. Near equal amounts of guanine (G) and adenine (A) were observed at the second base position of codon 61. The wild-type (GAG) and mutated (GGG) sequences found in codon 61 correspond to glutamic acid (Glu) and glycine (Gly) residues, amino acids which differ in mass by -72 Da. Mass spectrometric analyses of TTR immunoprecipitated from serum showed the presence of both wild-type and variant proteins. The observed mass results for the wild-type and variant proteins were consistent with the predicted values calculated from the genetic analysis data. 相似文献
992.
N Deb-Joardar N Germain G Thuret A -F Garcin P Manoli A Defreyn P Gain B Estour 《Diabetic medicine》2007,24(3):303-307
AIMS: Screening for diabetic retinopathy (DR) is highly inadequate in France because of insufficient infrastructure and increasing disease prevalence. We describe the results of the first systematic DR screening programme established in a university diabetes department. METHODS: In this cross-sectional study conducted over 1 year, consecutive adult patients underwent three-field retinal photography with the Topcon TRC NW6S digital fundus camera following pupillary dilatation with Tropicamide 1%. A questionnaire provided information on patients' systemic and ocular history. Glycated haemoglobin (HbA1c) was measured at the screening visit.Two ophthalmologists graded the retinal photographs in a masked fashion. RESULTS: Of 1157 patients attending the diabetes department, 1153 (99.7%)underwent photographic screening. Images were gradable in 96% patients.Diabetic retinopathy was detected in 522 (45%) patients and sight-threatening DR in 167 (14%). Of 704 (61%) patients previously believed to have no DR,254 (34%) screened positive. The presence of DR was associated with age,insulin use and non-Caucasian ethnicity in Type 2 patients, and with duration of diabetes and HbA1c in Type 1 and Type 2 patients. Associated ocular pathologies were diagnosed in 612 (53%) patients. CONCLUSIONS: Our photographic screening programme using pharmacological mydriasis provided a high screening coverage feasible in a hospital setting. We obtained information regarding prevalence and associated risk factors of DR inpatients attending a tertiary care centre. Screening was well accepted by patients and met with no protest from city ophthalmologists. It generated considerable interest among endocrinologists and feedback of results is expected to improve optimization of glycaemic control. 相似文献
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The β‐adhesin part of the Porphyromonas gingivalis W50 (ATCC 53978) protease HRgpA was cloned in an eukaryotic expression vector and expressed in COS‐7 cells. The monoclonal antibody MAb (61BG1.3), specific for the hemagglutinating domain of β‐adhesin, recognized the expressed β‐adhesin in the transfected cells both by immunoblot and immunofluorescence. Sprague Dawley rats were immunized intramuscularly with β‐adhesin encoding expression plasmid and expression plasmid without β‐adhesin insert. Skeletal muscle tissue at the site of immunization in the β‐adhesin immunized animals was shown to express this protein. The immunization induced a β‐adhesin‐specific antibody response. Sera from the immunized animals were tested for hemagglutination inhibiting activity. Due to high natural inhibiting activity in all rat sera tested, no increased hemagglutination inhibition was detected in sera from the β‐adhesin immunized animals. 相似文献
996.
Scott S Auerbach Joshua G Dekeyser Matthew A Stoner Curtis J Omiecinski 《Drug metabolism and disposition》2007,35(3):428-439
The constitutive androstane receptor (CAR; NR1I3) regulates the expression of genes involved in xenobiotic metabolism. Alternative splicing of the human CAR gene yields an array of mRNAs that encode structurally diverse proteins. One form of CAR, termed CAR2, contains an additional four amino acids (SPTV) that are predicted to reshape the ligand-binding pocket. The current studies show a marked, ligand-independent, CAR2-mediated transactivation of reporters containing optimal DR-3, DR-4, and DR-5 response elements, and reporters derived from the natural CYP2B6 and CYP3A4 gene promoters. Overexpression of the RXRalpha ligand binding domain was critical for achieving these effects. CAR2 interaction with SRC-1 was similarly dependent on the coexpression of RXRalpha. Mutagenesis of Ser233 (SPTV) to an alanine residue yielded a receptor possessing higher constitutive activity. Alternatively, mutating Ser233 to an aspartate residue drastically reduced the transactivation capacity of CAR2. The respective abilities of these mutagenized forms of CAR2 to transactivate a DR-4 x 3 reporter element correlated with their ability to interact with RxRalpha and to recruit SRC-1 in a ligand-regulated manner. Together, these results demonstrate a robust RXRalpha-dependent recruitment of coactivators and transactivation by CAR2. In addition, CAR2 displays novel dose responses to clotrimazole and androstanol compared with the reference form of the receptor while at the same time retaining the ability to bind CITCO. This result supports a hypothesis whereby the four-amino-acid insertion in CAR2 structurally modifies its ligand binding pocket, suggesting that CAR2 is regulated by a set of ligands distinct from those governing the activity of reference CAR. 相似文献
997.
OBJECTIVE: The authors examined whether physicians' use of computerized decision aids affects patient satisfaction and/or blame for medical outcomes. METHOD: Experiment 1: Fifty-nine undergraduates read about a doctor who made either a correct or incorrect diagnosis and either used a decision aid or did not. All rated the quality of the doctor's decision and the likelihood of recommending the doctor. Those receiving a negative outcome also rated negligence and likelihood of suing. Experiment 2: One hundred sixty-six medical students and 154 undergraduates read negative-outcome scenarios in which a doctor either agreed with the aid, heeded the aid against his own opinion, defied the aid in favor of his own opinion, or did not use a decision aid. Subjects rated doctor fault and competence and the appropriateness of using decision aids in medicine. Medical students made judgments for themselves and for a layperson. RESULTS: Experiment 1: Using a decision aid caused a positive outcome to be rated less positively and a negative outcome to be rated less negatively. Experiment 2: Agreeing with or heeding the aid was associated with reduced fault, whereas defying the aid was associated with roughly the same fault as not using one at all. Medical students were less harsh than undergraduates but accurately predicted undergraduate's responses. CONCLUSION: Agreeing with or heeding a decision aid, but not defying it, may reduce liability after an error. However, using an aid may reduce favorability after a positive outcome. 相似文献
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