Organization and sequence of the gene encoding the human acrosin-trypsin inhibitor (HUSI-II)

A complete cDNA encoding the acrosin-trypsin inhibitor, HUSI-II, was used as a probe to isolate genomic clones from a human placenta library. Three clones which cover the entire HUSI-II gene were isolated and characterized. The exon-intron organization of the gene was determined and found to be identical to other known Kazal-type inhibitor-encoding genes. The striking similarity in the amino acid sequences which was found previously in HUSI-II and glycoprotein hormone β-subunits, is neither reflected in codon usage nor in the exon-intron arrangement of the genes. A 1.8-kb segment 5′ of the gene was sequenced. The analysis of this sequence showed that HUSI-II contains a G + C-rich region upstream from the transcription start point (tsp) which fulfills the criteria for a CpG island. Furthermore, in the first intron, a potential glucocorticoid-responsive element was found as a half-palindrome flanked by two CACCC elements. Determination of the tsp by S1 mapping revealed that HUSI-II has multiple tsp. Genomic Southern hybridization was used to show that HUSI-II is a single-copy gene. The localization of the gene to chromosome 4 was determined by hybridization of a 5′ genomic fragment to the DNA of a panel of somatic hybrids between human and rodent cells

A critical role for the Sp1-binding sites in the transforming growth factor-β-mediated inhibition of lipoprotein lipase gene expression in macrophages

Increasing evidence suggests that the cytokine transforming growth factor-β (TGF-β) inhibits the development of atherosclerosis. The lipoprotein lipase (LPL) enzyme expressed by macrophages has been implicated in the pathogenesis of atherosclerosis by stimulating the uptake of lipoprotein particles. Unfortunately, the action of TGF-β on the expression of LPL in macrophages remains largely unclear. We show that TGF-β inhibits LPL gene expression at the transcriptional level. Transient transfection assays reveal that the −31/+187 sequence contains the minimal TGF-β-responsive elements. Electrophoretic mobility shift assays show that Sp1 and Sp3 interact with two regions in the −31/+187 sequence. Mutations of these Sp1/Sp3 sites abolish the TGF-β-mediated suppression whereas multimers of the sequence impart the response to a heterologous promoter. TGF-β has no effect on the binding or steady-state polypeptide levels of Sp1 and Sp3. These results, therefore, suggest a novel mechanism for the TGF-β-mediated repression of LPL gene transcription that involves regulation of the action of Sp1 and Sp3

Outcomes, experiences and palliative care in major stroke:a multicentre, mixed-method, longitudinal study

Background: Case fatality after total anterior circulation stroke is high. Our objective was to describe the experiences and needs of patients and caregivers, and to explore whether, and how, palliative care should be integrated into stroke care. Methods: From 3 stroke services in Scotland, we recruited a purposive sample of people with total anterior circulation stroke, and conducted serial, qualitative interviews with them and their informal and professional caregivers at 6 weeks, 6 months and 1 year. Interviews were transcribed for thematic and narrative analysis. The Palliative Care Outcome Scale, EuroQol-5D-5L and Caregiver Strain Index questionnaires were completed after interviews. We also conducted a data linkage study of all patients with anterior circulation stroke admitted to the 3 services over 6 months, which included case fatality, place of death and readmissions. Results: Data linkage (n = 219) showed that 57% of patients with total anterior circulation stroke died within 6 months. The questionnaires recorded that the patients experienced immediate and persistent emotional distress and poor quality of life. We conducted 99 interviews with 34 patients and their informal and professional careers. We identified several major themes. Patients and caregivers faced death or a life not worth living. Those who survived felt grief for a former life. Professionals focused on physical rehabilitation rather than preparation for death or limited recovery. Future planning was challenging. “Palliative care” had connotations of treatment withdrawal and imminent death. Interpretation: Major stroke brings likelihood of death but little preparation. Realistic planning with patients and informal caregivers should be offered, raising the possibility of death or survival with disability. Practising the principles of palliative care is needed, but the term “palliative care” should be avoided or reframed

Faking like a woman? Towards an interpretative theorization of sexual pleasure.

This article explores the possibility of developing a feminist approach to gendered and sexual embodiment which is rooted in the pragmatist/interactionist tradition derived from G.H. Mead, but which in turn develops this perspective by inflecting it through more recent feminist thinking. In so doing we seek to rebalance some of the rather abstract work on gender and embodiment by focusing on an instance of 'heterosexual' everyday/night life - the production of the female orgasm. Through engaging with feminist and interactionist work, we develop an approach to embodied sexual pleasure that emphasizes the sociality of sexual practices and of reflexive sexual selves. We argue that sexual practices and experiences must be understood in social context, taking account of the situatedness of sex as well as wider socio-cultural processes the production of sexual desire and sexual pleasure (or their non-production) always entails interpretive, interactional processes

Narratives of self and identity in women's prisons: stigma and the struggle for self-definition in penal regimes

A concern with questions of selfhood and identity has been central to penal practices in women's prisons, and to the sociology of women's imprisonment. Studies of women's prisons have remained preoccupied with women prisoners’ social identities, and their apparent tendency to adapt to imprisonment through relationships. This article explores the narratives of women in two English prisons to demonstrate the importance of the self as a site of meaning for prisoners and the central place of identity in micro-level power negotiations in prisons

Beyond words: Aesthetic knowledge and knowing in design

Aesthetic knowledge comes from practitioners understanding the look, feel, smell, taste and sound of things. It is vital to work in many organizational contexts. In this paper, we explore aesthetic knowledge and knowing in organizations through detailed observation of design work in the architectural practice Edward Cullinan Architects. Through our research, we explore aesthetic knowledge in the context of architectural work, we unpack what it is, how it is generated, and how it is applied in design projects, shared between practitioners and developed at the level of the organization. Our analysis suggests that aesthetic knowledge plays an important part in organizational practice, not only as the symbolic context for work, but as an integral part of the work that people do. It suggests that aesthetic reflexivity, which involves an opening up and questioning of what is known, is experienced as part of practice as well as a `time out' from practice

Decorin reduces intraocular pressure and retinal ganglion cell loss in rodents through fibrolysis of the scarred trabecular meshwork

Purpose. To investigate whether Decorin, a matrikine that regulates extracellular matrix (ECM) deposition, can reverse established trabecular meshwork (TM) fibrosis, lower IOP, and reduce progressive retinal ganglion cell (RGC) death in a novel rodent model of TM fibrosis. Methods. Adult rats had intracameral (IC) injections of human recombinant (hr) TGF-β over 30 days (30d; to induce TM fibrosis, raise IOP, and initiate RGC death by 17d) or PBS (controls) and visually evoked potentials (VEP) were measured at 30d to evaluate resultant visual pathway dysfunction. In some animals TGF-β injections were stopped at 17d when TM fibrosis and IOP were consistently raised and either hrDecorin or PBS IC injections were administered between 21d and 30d. Intraocular pressure was measured biweekly and eyes were processed for immunohistochemical analysis of ECM deposition to assess TM fibrosis and levels of matrix metalloproteinases (MMP) and tissue inhibitors of matrix metalloproteinases (TIMP) to assess fibrolysis. The effect of hrDecorin treatment on RGC survival was also assessed. Results. Transforming growth factor–β injections caused sustained increases in ECM deposition in the TM and raised IOP by 17d, responses that were associated with 42% RGC loss and a significant decrease in VEP amplitude measured at 30d. Decorin treatment from 17d reduced TGF-β–induced TM fibrosis, increased levels of MMP2 and MMP9 and lowered TIMP2 levels, and lowered IOP, preventing progressive RGC loss. Conclusions. Human recombinant Decorin reversed established TM fibrosis and lowered IOP, thereby rescuing RGC from progressive death. These data provide evidence for the candidacy of hrDecorin as a treatment for open-angle glaucoma

ON THE PRAGMATICS OF SOCIAL THEORY: THE CASE OF ELIAS'S "ON THE PROCESS OF CIVILIZATION".

This paper proposes a new approach to the study of sociological classics. This approach is pragmatic in character. It draws upon the social pragmatism of G. H. Mead and the sociology of texts of D. F. McKenzie. Our object of study is Norbert Elias's On the Process of Civilization. The pragmatic genealogy of this book reveals the importance of taking materiality seriously. By documenting the successive entanglements between human agency and nonhuman factors, we discuss the origins of the book in the 1930s, how it was forgotten for 30 years, and how in the mid-1970s it became a sociological classic. We explain canonization as a matter of fusion between book's material form and its content, in the context of the paperback revolution of the 1960s, the events of May 1968, and the demise of Parsons' structural functionalism, and how this provided Elias with an opportunity to advance his model of sociology.This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by Wiley