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91.
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Greene CM Miller SD Carroll T McLean C O'Mahony M Lawless MW O'Neill SJ Taggart CC McElvaney NG 《Journal of inherited metabolic disease》2008,31(1):21-34
Summary Alpha-1 antitrypsin (A1AT) is a serine anti-protease produced chiefly by the liver. A1AT deficiency is a genetic disorder
characterized by serum levels of less than 11 μmol/L and is associated with liver and lung manifestations. The liver disease,
which occurs in up to 15% of A1AT-deficient individuals, is a result of toxic gain-of-function mutations in the A1AT gene,
which cause the A1AT protein to fold aberrantly and accumulate in the endoplasmic reticulum of hepatocytes. The lung disease
is associated with loss-of-function, specifically decreased anti-protease protection on the airway epithelial surface. The
so-called ‘Z’ mutation in A1AT deficiency encodes a glutamic acid-to-lysine substitution at position 342 in A1AT and is the
most common A1AT allele associated with disease. Here we review the current understanding of the molecular pathogenesis of
A1AT deficiency and the best clinical management protocols.
Competing interests: None declared
References to electronic databases: Alpha 1-antitrypsin deficiency: +107400.
C.M. Greene and S.D.W. Miller contributed equally to the work. 相似文献
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B C Tennant N Mrosovsky K McLean P J Cote B E Korba R E Engle J L Gerin J Wright G R Michener E Uhl 《Hepatology (Baltimore, Md.)》1991,13(6):1215-1221
During studies of seasonal obesity, a high frequency of hepatic neoplasms was observed in Richardson's ground squirrels. Of 12 Richardson's ground squirrels examined thoroughly, 7 had mild or moderate degrees of chronic portal hepatitis and 6 (50%) had hepatocellular carcinoma. Serological tests for hepadnavirus surface antigen, anti-core antibody and virion DNA that recognize the ground squirrel hepatitis virus of California ground squirrels (Spermophilus beecheyi) were uniformly negative. Southern blot analyses of EcoRI digests of liver cell DNA demonstrated 3.2 kb fragments that hybridized with a ground squirrel hepatitis virus-specific probe in nontumorous liver tissue from 6 of 10 ground squirrels and in hepatocellular carcinoma specimens from 2 of 5 squirrels indicating infection with a hepadnavirus related to ground squirrel hepatitis virus. Failure, however, to detect serum antibody to ground squirrel hepatitis core antigen suggested probable antigenic differences between the ground squirrel hepatitis virus of California ground squirrels and the putative Richardson's ground squirrel agent. Further studies are required to fully characterize the hepadnavirus of Richardson's ground squirrels and to determine its relationship to hepatocarcinogenesis in this species. 相似文献
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Katherine McLean 《Addiction Research & Theory》2015,23(6):490-498
This article considers individuals' diverse modes of engagement with an increasingly medicalised strain of harm reduction that emphasises individual accountability for personal health and welfare. Drawing upon 1 year of ethnographic research at a New York City-based syringe exchange (“NYC Harm Reduction”, a pseudonym), I describe how drug users themselves made sense of harm reduction, negotiated its discourses of risk and responsibility, and incorporated its behavioural directives into their own body projects – or did not. While suggesting some participants' apparent absorption of risk reduction into a dominant, and enabling identity, I focus mainly upon individuals' “on-stage” performances and apparent depth of service use and acceptance while at NYC Harm Reduction. Building upon recent critiques of contemporary harm reduction's de-contextualised neoliberal subject, I discuss the crucial roles of public housing assistance and peer worker employment in incentivising participants' uptake of pro-risk reduction attitudes, and (presumably) practices. Ultimately, participants' multiplicity of approaches to harm reduction hinged upon differences in not only personality or stage of drug use, but also current living circumstances; moreover, individuals' differential engagement with NYC Harm Reduction reflected the ways in which the organisation and its government funders prioritised the material investment of certain “risky” bodies – namely, HIV-positive drug users. 相似文献
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W S McLean A A Smith V Hansson O Naess S N Nayfeh F S French 《Molecular and cellular endocrinology》1976,4(4):239-255
Immature rat testes contain a specific binding protein for testosterone (T) and 5alpha-dihyrotestosterone (DHT) with physico-chemical properties similar to the cytoplasmic androgen receptors in the epididymis and ventral prostate but different from the testicular androgen-binding protein (ABP). Like the androgen receptors in the prostate and epididymis, it has a sedimentation coefficient of about 7 S at low ionic strength, is eluted in or close to the void volume on Sephadex G-200 gel filtration (Stokes radius greater than 80 A), has an isoelectric point of about 5.6-6.0 (mean) 5.8 and a relative mobility (Rf) of 0.4 in 3.25% acrylamide gels. Following the injection of 3H-labeled testosterone, T and DHT are bound selectively by the receptor. Relatively more [3H]T than [3H]DHT is present in bound and free fractions as well as in total testicular 105,000 g supernatant. Similar results are obtained from testicular incubations with equimolar amounts of [3H]T and [3H]DHT at 0 degrees C in vitro. Saturation of receptor sites is achieved by incubation of testis supernatants with increasing amounts of [3H]T at 0 degrees C. The number of available binding sites following post-hypophysectomy regression is estimated to be about 9 fmoles/mg protein, and the apparent equilibrium constant of dissociation is 7 X 10(-10) M. The temperature stability and sulfhydryl dependence of the testicular androgen receptor are similar to androgen receptors in other organs. Binding is destroyed by heating the supernatants at 50 degrees C for 30 min and by exposure to p-chloromercuriphenylsulfonate (1 mM) at 0 degrees C for 60 min. Furthermore, like other androgen receptors, the half-time of dissociation of testicular androgen-receptor complexes at 0 degrees C is extremely slow (t1/2 greater than 35 h). Separation of seminiferous tubules from interstitial tissue showed that a major portion of these receptors were localized within the seminiferous tubules. 相似文献
96.
A M Johnson A Petherick S J Davidson R Brettle M Hooker L Howard K A McLean L E Osborne R Robertson C Sonnex 《AIDS (London, England)》1989,3(6):367-372
Future heterosexual spread of HIV will in part depend on the efficiency of transmission from men to women and from women to men. We studied seventy-eight female sexual partners of men infected with HIV and 18 male sexual partners of infected women. Participants were interviewed concerning sexual practices, use of contraception and other risk factors for HIV infection. Fifteen out of 78 (19.2%) female partners and one out of eighteen (5.5%) male partners were seropositive for HIV antibody. All couples had practised vaginal intercourse. Seropositive female partners did not differ significantly from seronegative partners with regard to length of relationship, number of acts of vaginal intercourse, other sexual practices, stage of clinical disease in the index case, or numbers of other sexual partners in the last five years. In two women, seroconversion was documented after one act of unprotected sexual intercourse. The majority of infected female partners (eight out of 15) had sexual relationships with men who were asymptomatic and did not practice anal intercourse. Biological factors such as variability in infectivity of the index case and susceptibility of the contact, as well as behavioural variables may be important in determining transmission. 相似文献
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Dietary restraint of 5‐year‐old girls: Associations with internalization of the thin ideal and maternal,media, and peer influences
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