Content and method trends in the Journal of Community Psychology between 2003 and 2007

Ongoing inquiry into the characteristics of published work and its synergy with community psychology's core principles is an important reflexive endeavour in the field's continuing development. This study examined topic and method trends within the Journal of Community Psychology during a 5‐year period (January 2003–December 2007). Content analyses were conducted on published abstracts during this period (N=242). Most articles were empirical studies (61.2%) and most used a positivist methodology (53.7%). Samples mainly comprised adults and were mixed in terms of gender and ethnic/religious affiliation. The most frequent topics were mental health and mental illness (33.5%), sense of community and social support (24.4%), and dynamics of social exclusion (22.7%). A large proportion of special issues was also noted. These results illustrate contemporary trends in community psychology and suggest that critical and participatory methods as well as socially transformative epistemologies continue to be under‐represented within the field. © 2011 Wiley Periodicals, Inc.     

Binding of SLE autoantibodies to native poly(I), ROS-poly(I) and native DNA: a comparative study.

Reactive oxygen species (ROS) are implicated in a variety of human diseases. The formation of pathogenic anti-DNA antibodies in systemic lupus erythematosus (SLE) has been extensively investigated. ROS-modified DNA has been found to be a better antigen for anti-DNA antibodies found in SLE sera. A comparative binding of SLE autoantibodies with native poly(I), ROS-poly(I) and nDNA has been studied. Affinity-purified SLE IgG exhibited a high degree of specificity towards the ROS-modified poly(I) in comparison to native DNA and native poly(I), reiterated visually by gel retardation assay. The data suggested that hydroxyl radical-modified nucleic acids like RNA and DNA might be agent for the induction of circulating SLE anti-DNA autoantibodies.     

Protein tyrosine phosphatase receptor-type O (PTPRO) exhibits characteristics of a candidate tumor suppressor in human lung cancer

Previous study in our laboratory demonstrated suppression of the gene for protein tyrosine phosphatase receptor-type O (PTPRO) in primary and established rat hepatomas. The present study showed methylation-mediated silencing of this gene in primary human lung tumors and in several human lung cancer cell lines, one of the characteristics of many tumor-suppressor genes. The reduced expression of PTPRO in the primary lung tumors correlated with the methylation status of its CpG island. Demethylation of the gene by deoxy-5-azacytidine treatment led to its reactivation in a lung cancer line (A549). Overexpression of PTPRO in A549 cells inhibited anchorage-independent growth, delayed reentry of the cells into the cell cycle after release from cell-cycle arrest, and increased susceptibility of the cells to apoptosis. These data have demonstrated the growth-suppressor characteristics of PTPRO that are unique to a classical tumor suppressor.     

Sensitization of Pancreatic Cancers to Gemcitabine Chemoradiation by WEE1 Kinase Inhibition Depends on Homologous Recombination Repair

To improve the efficacy of chemoradiation therapy for locally advanced pancreatic cancer and begin to establish patient selection criteria, we investigated the combination of the WEE1 inhibitor AZD1775 with gemcitabine-radiation in homologous recombination (HR) repair proficient and deficient pancreatic cancers. Sensitization to gemcitabine-radiation by AZD1775 was assessed in pancreatic cancer cells by clonogenic survival and in patient-derived xenografts by tumor growth. The contributions of HR repair inhibition and G2 checkpoint abrogation to sensitization were assessed by γH2AX, BRCA2 manipulation, and RAD51 focus formation and pHistone H3 flow cytometry, respectively. We found that AZD1775 sensitized to gemcitabine-radiation in BRCA2 wild-type but not BRCA2 mutant pancreatic cancer cells. In all cells, AZD1775 caused inhibition of CDK1 phosphorylation and G2 checkpoint abrogation. However, sensitization by AZD1775 was associated with persistent γH2AX and inhibition of RAD51 focus formation. In HR-proficient (BRCA2 wild-type) or -deficient (BRAC2 null) isogenic cells, AZD1775 sensitized to gemcitabine-radiation in BRCA2 wild-type, but not in BRCA2 null cells, despite significant G2 checkpoint abrogation. In patient-derived pancreatic tumor xenografts, AZD1775 significantly inhibited tumor growth and impaired RAD51 focus formation in response to gemcitabine-radiation. In conclusion, WEE1 inhibition by AZD1775 is an effective strategy for sensitizing pancreatic cancers to gemcitabine chemoradiation. Although this sensitization is accompanied by inhibition of CDK1 phosphorylation and G2 checkpoint abrogation, this mechanism is not sufficient for sensitization. Our findings demonstrate that sensitization to chemoradiation by WEE1 inhibition results from inhibition of HR repair and suggest that patient tumors without underlying HR defects would benefit most from this therapy.Abbreviations: DSB, double-strand break; HR, homologous recombination; RER, radiation enhancement ratio; RT, radiation     

Use of the levonorgestrel-releasing intrauterine system in renal transplant recipients: a retrospective case review

Our objective was to report on the use of the levonorgestrel-releasing intrauterine system (LNG-IUS, Mirena®) in renal transplant recipients.A retrospective case review was done to identify renal transplant recipients for whom a LNG-IUS had been inserted. All of the women had been seen in the Gynecology Department, Beaumont Hospital, during the period 2000 to 2010. Parameters including age, year of transplantation, indication for insertion, duration of use, discontinuation and complications were documented.The main outcome measure was discontinuation of the LNG-IUS due to pelvic infection.Eleven women were identified who had undergone renal transplantation and were using the LNG-IUS. The mean duration of use was 38 (range 1–84) months. Four women were using the LNG-IUS for contraception and seven were using it for the treatment of menorrhagia, either alone or in conjunction with endometrial ablative procedures. One woman discontinued use in order to conceive. There were no unplanned pregnancies. There were no documented cases of pelvic infection in women using the device.Renal transplant recipients have a critical need for safe and effective contraception. The use of the LNG-IUS has been avoided in the patients due to the theoretical risk of intrauterine device-related pelvic infection in immune-suppressed patients. However, on the basis of our results, we believe that it is acceptable to use the LNG-IUS in renal transplant recipients for both contraception and for the treatment of menorrhagia as the theoretical risk of infection in these immune-suppressed patients does not appear to be increased.     

Serine residues 338 and 339 in the carboxyl-terminal tail of the type II gonadotropin-releasing hormone receptor are critical for beta-arrestin-independent internalization

Cloned mammalian type II GnRH receptors have a carboxyl-terminal tail in contrast to the mammalian type I GnRH receptors, which uniquely lack a carboxyl-terminal tail. Because this domain mediates internalization of many serpentine receptors, the internalization pathway of the marmoset monkey type II GnRH receptor and the functional role of the carboxyl-terminal tail in internalization was studied. The internalization pathway of the type II GnRH receptor was investigated in COS-1 cells by coexpressing G protein-coupled receptor kinases (GRKs), dynamin-1, and beta-arrestins. Internalization of the receptor requires GRKs and dynamin but does not require beta-arrestin. The type II GnRH receptor can also internalize via beta-arrestin in the presence of exogenous beta-arrestins, suggesting that the receptor can use two distinct internalization pathways. Receptor internalization appears to occur via clathrin-coated pits and caveolae because disruption of either structure inhibits internalization. Progressive truncations of the carboxyl-terminal tail identified a region containing serine residues 338 and 339 as critical for receptor internalization. Substitution of these serine residues with alanine residues inhibited internalization, whereas substitutions with glutamic acid residues rescued internalization. Furthermore, a dominant-negative GRK2 did not inhibit internalization of receptors having these serine substitutions, although it inhibited internalization of the wild-type receptor. These results together identify serine residues 338 and 339 in the carboxyl-terminal tail as critical for internalization of the type II GnRH receptor and suggest that these residues undergo phosphorylation by GRKs. However, neither of these residues, nor the carboxyl-terminal tail, is required for beta-arrestin-dependent internalization.