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1.
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
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Infection with larval trematodes has been shown to inhibit several snail-host defences, including hemocyte phagocytosis, cytotoxicity, motility, and adherence. Certain plasma factors which mediate snail defence responses, and which may be produced by host hemocytes, also appear to be altered by these parasites. In this study we present protocols for the isolation of 2 proteins from larval Schistosoma mansoni excretory-secretory (ES) products and detail the effects of these components on Biomphalaria glabrata hemocyte protein synthetic/secretory (S/S) activity. Schistosome ES proteins, separated with a combination of membrane ultrafiltration, size exclusion, and ion exchange chromatography, were tested for their in vitro effect on cultured snail hemocytes, in the presence and absence of homologous plasma. A high-molecular-weight ultrafiltration fraction of parasite ES products (H30), in combination with plasma, was found to differentially affect susceptible (M-line) and resistant (10-R2) snail hemocytes. Secretion of metabolically labeled polypeptides by M-line cells was inhibited significantly while the S/S response of 10-R2 hemocyte polypeptides was not affected. In the absence of homologous plasma, little or no differential affect of ES polypeptides on hemocyte S/S activity was seen. Much of the inhibitory activity of H30 was attributable to a partially purified fraction, Peak I (PkI), of ES products. Evidence suggests that, in its native state, PkI is a high-molecular-weight protein aggregate comprising subunits of approximately 22-24 kDa. Thus, PkI, in the presence of homologous plasma components, is a potential mediator of schistosome-induced suppression of polypeptide synthesis or secretion in hemocytes of susceptible snails. In combination with other parasite and host factors, PkI may be involved in the host-parasite interaction which leads to the state of susceptibility or resistance found in our strains of B. glabrata. 相似文献
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Contrasting binge and continuous alcoholic drinkers using demographic and drinking history variables 总被引:1,自引:1,他引:0
G J Connors A R Tarbox E J McLaughlin 《Alcohol and alcoholism (Oxford, Oxfordshire)》1986,21(1):105-110
While it is quite common for researchers and clinicians to categorize alcoholics as binge or continuous drinkers, relatively little is known about the characteristics of these two potentially distinct clinical populations. In the present study, binge and continuous alcoholics were evaluated on a number of demographic and drinking history variables. Binge drinkers were found to be significantly more likely than continuous drinkers to have been treated for liver problems and more likely to have reported parental alcoholism. They also tended to describe a greater number of alcohol-related arrests and hospitalizations. Six of the variables taken together yielded a discriminative function that was only moderately successful in classifying these drinkers. The potential clinical importance of objectively identifying binge versus continuous drinkers is discussed. 相似文献