Erratum15 March 2002free access Intracellular trafficking pathway of newly synthesized CD1b molecules V. Briken V. Briken Search for more papers by this author R.M. Jackman R.M. Jackman Search for more papers by this author S. Dasgupta S. Dasgupta Search for more papers by this author S. Hoening S. Hoening Search for more papers by this author S.A. Porcelli S.A. Porcelli Search for more papers by this author V. Briken V. Briken Search for more papers by this author R.M. Jackman R.M. Jackman Search for more papers by this author S. Dasgupta S. Dasgupta Search for more papers by this author S. Hoening S. Hoening Search for more papers by this author S.A. Porcelli S.A. Porcelli Search for more papers by this author Author Information V. Briken, R.M. Jackman, S. Dasgupta, S. Hoening and S.A. Porcelli The EMBO Journal (2002)21:1504-1504https://doi.org/10.1093/emboj/21.6.1504 This article corrects the following: Intracellular trafficking pathway of newly synthesized CD1b molecules15 February 2002 PDFDownload PDF of article text and main figures. ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InMendeleyWechatReddit Figures & Info The EMBO Journal, 21, 825–834, 2001 In the above paper, the names of two cytoplasmic tail peptides were incorrectly printed in Table I. The correct version should read: Table 1. Overview of cytoplasmic tail peptide interactions with AP-2 or AP-3 Tail AP-2 AP-3 ka (1/M×s) kd (1/s) KD (μM) ka (1/M×s) kd (1/s) KD (μM) CD1c wt 1.9 × 104 5.6 × 10−3 0.29 3.4 × 102 4.7 × 10−3 14.0 CD1b wt 1.4 × 104 4.9 × 10−3 0.35 1.2 × 103 4.2 × 10−3 3.5 CD1b Y>A 1.2 × 103 5.3 × 10−3 4.4 0.3 × 103 4.0 × 10−3 13.3 Lamp-1 wt 2.6 × 104 3.1 × 10−3 0.12 9.2 × 102 3.4 × 10−3 3.7 Lamp-1 Y>A 8.7 × 103 3.9 × 10−3 4.5 2.7 × 102 3.9 × 10−3 14.4 TfR wt 1.2 × 105 4.6 × 10−3 0.04 and nd nd TfR Y,F>A 2.3 × 103 5.2 × 10−3 2.3 nd nd nd The interaction of purified AP-2 and AP-3 complexes with cytoplasmic tail peptides was analyzed by SPR using a BIAcore 3000 as described in Materials and methods. The rate constants for association (ka) and dissociation (kd) were determined at three different concentrations of AP-2 and AP-3 for each peptide. Shown are the values measured with AP-2 and AP-3 at 500 nM. The equilibrium dissociation constant (KD = kd/ka) was calculated for each adaptor concentration. Values obtained from three independent sets of measurements varied by 3–7%. a nd: not detectable. The publisher would like to apologize for this error and any confusion caused. Next ArticlePrevious Article Read MoreAbout the coverClose modalView large imageVolume 21,Issue 6,March 15, 2002Cover. This photograph of Les Calanques (from calanco, rock) was taken on the Mediterranean coast of France in a protected paradise covering some 5000 hectares. These sea creeks were formed after the ice age 12 000 years ago, when an increase in sea levels resulted in invasion of the valleys. The photographer, Luisa Figueiredo, is finishing her PhD at the Pasteur Institute (Paris), and will soon be moving to the Rockefeller University (New York) to continue her studies on the telomere biology of human parasites. Volume 21Issue 615 March 2002In this issue RelatedDetailsLoading ...

▪ Abstract This review evaluates the most recent studies of social capital in political science and argues that they have strayed considerably from the original treatment of social capital, which casts it as endogenous. Recent treatments have recast social capital as a feature of political culture and thereby treat values as exogenous. These two approaches emanate from incompatible premises and have fundamentally different implications. Thus, efforts to combine the two approaches are rendered unproductive by inevitable inconsistencies of internal logic. Moreover, empirical tests of the exogenous social capital approach are deficient: They are selective in their use of data and employ ad hoc procedures at crucial junctures. We therefore urge a return to the treatment of social capital as endogenous.

We have used our previously described ex vivo mesothelial cell (MC)-mediated gene therapy strategy (Gene Ther. 2:393-401, 1995) to modify the functional properties of the rat parietal peritoneal mesothelium in vivo by expression of a membrane-bound recombinant protein on the MC surface. Rat primary MCs were stably transfected (using strontium phosphate DNA coprecipitation) with a plasmid containing the gene for rat thrombomodulin (TM), a transmembrane glycoprotein that functions as an essential cofactor for the physiological activation of the anticoagulant protein C by the enzyme thrombin. As demonstrated by immunohistochemistry and by direct equilibrium binding with radiolabeled thrombin, genetically modified MCs expressed high levels of TM antigen on their surface in vitro. As judged by a thrombin-dependent protein C activation assay, such MC membrane-bound TM was biologically active. Once reseeded on the denuded parietal peritoneal surface of syngeneic recipients, these TM-transfected MCs continued to express TM antigen in vivo for at least 90 days. Moreover, the recombinant TM expressed on the reconstituted parietal mesothelium retained its ability to activate protein C in a thrombin-dependent manner. Our data indicate that MC-mediated expression of TM can be used to augment the anticoagulant properties of the parietal peritoneal surface. In general, our results suggest that ex vivo MC-mediated gene therapy can be used to deliver other therapeutic transmembrane proteins to the MC surface to enhance the functional repertoire of the parietal mesothelium in vivo.

Psoriatic skin is characterized by microvascular hyperpermeability and angioproliferation, but the mechanisms responsible are unknown. We report here that the hyperplastic epidermis of psoriatic skin expresses strikingly increased amounts of vascular permeability factor (VPF; vascular endothelial growth factor), a selective endothelial cell mitogen that enhances microvascular permeability. Moreover, two VPF receptors, kdr and flt-1, are overexpressed by papillary dermal microvascular endothelial cells. Transforming growth factor alpha (TGF-alpha), a cytokine that is also overexpressed in psoriatic epidermis, induced VPF gene expression by cultured epidermal keratinocytes. VPF secreted by TGF-alpha-stimulated keratinocytes was bioactive, as demonstrated by its mitogenic effect on dermal microvascular endothelial cells in vitro. Together, these findings suggest that TGF-alpha regulates VPF expression in psoriasis by an autocrine mechanism, leading to vascular hyperpermeability and angiogenesis. Similar mechanisms may operate in tumors and in healing skin wounds which also commonly express both VPF and TGF-alpha.

Theory: Cultural differences drive significant elements of political and economic life. Hypotheses: (1) effective govemance hinges critically on traditions of civic engagement; (2) political culture fundamentally drives economic performance and democratic stability. Method: Reanalysis of two data sets: (1) the first includes information collected by Putnam (1993) on a variety of political, economic and social indicators for the 20 Italian regions; (2) the second includes comparable information collected by Inglehart (1990) for the industrial democracies. Results: We find little evidence to indicate a systematic relationship between political culture and political and economic performance.

We examine the systemic conditions that have influenced the electoral success of parties of the extreme right in West European politics from 1970 through 1990. Empirical estimates based on 103 elections in sixteen countries suggest that electoral and party-system factors interact with each other to generate conditions conducive to these parties. Specifically, increasing electoral thresholds dampen support for the extreme right as the number of parliamentary parties expands. At the same time, multi-partism increasingly fosters parties of the extreme right with rising electoral proportionality. Our analyses also indicate that higher rates of unemployment provide a favourable environment for these political movements. These results suggest that levels of electoral support for the extreme right are sensitive to factors that can be modified through policy instruments.

The analyses reported by Granato, Inglehart, and Leblang (1996; hereafter GIL) are a major improvement over the studies that we examined in our paper. Especially notable is their explicit evaluation of the cultural explanation against a major rival, as represented by endogenous growth models of scholars like Barro (1991), Levine and Renelt (1992), and Helliwell (1994). These models regress economic growth rates over a given period on a set of initial economic, human capital, and other variables. It is in the context of such models that GIL report a significant, independent effect of culture on growth. GIL's attention to the robustness of their estimates contrasts sharply with the studies evaluated in Jackman and Miller (1996). Their analysis departs from recent treatments in another way. In contrast to Inglehart (1990), for example, who examines the seven different components of culture that we discuss, GIL restrict their attention to just two: postmaterialism and achievement motivation. They find that only achievement motivation affects growth, which serves as the basis for their conclusion about the importance of culture. In this sense, their work stands as a key amendment to recent studies with their emphasis on norms of trust, satisfaction, participation, and the like and signals a return to earlier work, exemplified most notably by McClelland's studies of need for achievement (1961; 1963; McClelland and Winter 1969). Given the exclusion of the former norms from GIL's analysis, along with their reported nonresults for postmaterialism, we take it that they regard achievement motivation as the only "cultural" value affecting economic growth. This narrows the field a good deal.' While there is thus much to recommend their paper over previous work, GIL's conclusion is ultimately unconvincing, on both theoretical and empirical grounds. We address these areas in turn.

There are two contending accounts of cross-national variation in voter turnout rates. One emphasizes the role of institutions and electoral attributes, whereas the other stresses cultural and historical factors. The authors evaluate the merits of these two arguments. They first apply the model developed by R. W. Jackman to turnout rates during the 1980s, expanding the sample of industrial states to include three newer democracies with recent authoritarian histories: Greece, Portugal, and Spain. They then examine the potential impact of cultural variables on voter turnout rates. The authors conclude that the institutional argument outperforms the cultural account of conventional political participation.

Delayed hypersensitivity (DH) is a T cell-mediated form of immune response characterized by a predominantly perivascular, mononuclear cell infiltrate. The venules in DH reactions are hyperpermeable to plasma proteins, leading to extravasation of plasma fibrinogen and its extravascular clotting to form a fibrin gel that promotes induration and angiogenesis. The mechanisms responsible for microvascular hyperpermeability in DH are unknown. Recently, a cytokine named vascular permeability factor (VPF, also known as vascular endothelial growth factor or VEGF) has been implicated in the chronic vascular hyperpermeability and angiogenesis of solid and ascites tumors, healing wounds, rheumatoid arthritis, and psoriasis. These findings suggested that VPF/VEGF might also have a role in the pathogenesis of DH. Two model systems were studied: allergic contact dermatitis to poison ivy in human volunteers and classical tuberculin hypersensitivity in rats. In both, in situ hybridization revealed that the mRNAs encoding VPF/VEGF were strikingly overexpressed in keratinocytes of the epidermis; scattered mononuclear cells infiltrating the dermis also overexpressed VPF/VEGF mRNA, to a greater extent in rat tuberculin than in human contact reactions. In contact reactions, mRNAs for two VPF/VEGF vascular endothelial cell receptors, flt-1 and KDR, were also strikingly overexpressed. Abundant fibrin deposition in both models confirmed that dermal microvessels were indeed hyperpermeable to plasma fibrinogen. These results implicate VPF/VEGF as a potentially important mediator in the pathogenesis of cell-mediated immunity and provide further evidence that products of epithelial cells may regulate the inflammatory response.

BACKGROUND Angiogenesis is a critical factor in the progression of solid tumors, including cervical cancers. The mechanisms responsible for angiogenesis in cervical neoplasia, however, are not well defined. PURPOSE Our goal was to determine the relationship between angiogenesis and the expression of the angiogenic cytokine vascular permeability factor (VPF), also known as vascular endothelial growth factor, and its receptors in cervical neoplasia. METHODS Sixty-six cervical biopsy specimens were evaluated; among these, 16 samples were designated as benign, 17 as low-grade squamous intraepithelial lesions, 18 as high-grade squamous intraepithelial lesions, and 15 as invasive squamous cell carcinomas. Histologic sections immunostained for factor VIII-related antigen were evaluated quantitatively for microvessel density and for the presence of epithelial-stromal vascular cuffing. Sections were also evaluated for VPF messenger RNA (mRNA) expression by in situ hybridization. RESULTS VPF mRNA expression, epithelial-stromal vascular cuffing, and microvessel density counts were significantly increased in invasive carcinoma and in high-grade intraepithelial lesions as compared with low-grade intraepithelial lesions and benign squamous epithelium. Vascular cuffing and increased microvessel density counts were also significantly associated with increased VPF mRNA expression. CONCLUSIONS These observations suggest that VPF is an important angiogenic factor in cervical neoplasia.

To evaluate the ability of genetically modified peritoneal mesothelial cells to deliver recombinant proteins to the systemic circulation, we used our previously described mesothelial cell-based ex vivo gene therapy strategy. Rat primary peritoneal mesothelial cells, isolated from parietal peritoneum by enzymatic digestion, were stably transfected (using strontium phosphate DNA co-precipitation) with the plasmid pSVTKgh to express a secreted reporter gene product, human growth hormone (hgh). Such hgh-secreting mesothelial cells were reseeded on the denuded peritoneal surface of syngeneic recipients and delivery of the reporter gene product to the systemic circulation was monitored by analysis of serum samples for the presence of hgh at various times after mesothelial cell implantation. Polymerase chain reaction (PCR) analysis demonstrated that the hgh-transfected mesothelial cells repopulated the denuded areas and remained attached there for at least 12 weeks. Moreover, these genetically modified mesothelial cells continued to express the reporter gene product in vivo and secreted hgh in sufficient quantity to be detected in the systemic circulation (ie statistically significant amounts of hgh could be measured in the serum of cyclosporine A-treated rats for at least 2 months; Mann-Whitney test, P < 0.05). Our results demonstrate the successful, sustained, systemic delivery of a recombinant protein by genetically modified peritoneal mesothelial cells following their reattachment to the peritoneal surface, and suggest the potential of ex vivo mesothelial cell-mediated gene therapy for the treatment of inherited or acquired disorders requiring delivery of therapeutic proteins to the circulation.

M uller's (1995) conclusion that income inequality has a major impact on rates of democratization continues a line of thought from Muller (1988) and Muller and Seligson (1994), and is at odds with our earlier empirical results (Bollen and Jackman 1985a). The major difference between Muller (1988) and Muller (1995) is that he is now more concerned with accounting for changes in democracy, whereas in the earlier paper he sought to explain of stable democracy. To measure change in political democracy, Muller (1995) uses 1965 and 1980 measures of developed by Bollen (1980, 1993), in lieu of his own earlier years of stable democracy measure. Muller's analysis is not compelling, on two counts. First, he fails to provide a convincing rationale for the hypothesized link between inequality and rates of democratization. Second, using his data, we find that his results are not robust, but instead are sensitive to plausible respecifications of the model.

We have developed a model system in the rat to test the feasibility of recombinant protein expression by genetically modified peritoneal mesothelial cells following autologous peritoneal implantation. Rat primary peritoneal mesothelial cells, isolated from parietal peritoneum by enzymatic digestion, were stably transduced (using a Moloney murine leukemia virus (MoMLV)-derived retroviral vector, BAG, expressing the Escherichia coli lacZ gene) to mark the cells with a reporter protein (beta-galactosidase, beta-gal). Such transduced mesothelial cells, tagged with DiO, a fluorescent lipophilic dye used for long-term tracing of transplanted cells, were then reseeded on the denuded peritoneal surface of syngeneic recipients. DiO-labeled, BAG-transduced mesothelial cells were observed to repopulate the denuded areas and remain attached there for > 90 days. Moreover, these genetically modified mesothelial cells continued to express the reporter gene product in vivo (ie beta-gal activity was present for at least 1 month). Our results demonstrate the feasibility of ex vivo gene therapy using peritoneal mesothelial cells.

Thrombomodulin is a vascular endothelial cell transmembrane protein that forms a 1:1 complex with thrombin, this interaction product forming the basis of a physiologically important natural anticoagulant system. Transcriptional down-regulation of thrombomodulin occurs following exposure of cultured endothelial cells to cytokines, while up-regulation is induced by retinoic acid and dibutyryl cyclic AMP. Thrombomodulin is also regulated developmentally, appearing in the parietal endoderm of 7.5-day-old mouse embryos. We determined that cell surface functional thrombomodulin in cultured human umbilical vein endothelial cells (HUVEC) and A549 cells increased 3.2- and 6.7-fold, respectively, in response to 24 h of continuous 42 degrees C heat shock stress. Northern analyses of thrombomodulin mRNA accumulation also showed a delayed response that was characterized by an augmentation in mRNA levels that started 12-18 h after the initiation of the stress, and continued to rise, without attenuation, during 48 h of continuous heat shock. Nuclear run-on studies confirmed that the predominant mechanism of augmentation was transcriptional. Furthermore, the heat shock-induced up-regulation of thrombomodulin in HUVEC abrogated the suppressive effect of tumor necrosis factor. Analysis of the 5' region of the thrombomodulin gene revealed six highly conserved tandem copies of the five base pair recognition unit that is the consensus sequence for a heat shock element. We hypothesize that the stress-induced augmentation in thrombomodulin gene transcription is mediated via heat shock factors binding to the heat shock element and that the stress response of thrombomodulin may have a biological role to protect the vascular endothelium during a variety of stresses, including inflammation, infection, and/or development.