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Performance measurement is touted as an important mechanism for organizational accountability in industrialized countries. This paper describes a systematic review of business and health performance measurement literature to inform a research agenda on healthcare performance measurement.A search of the peer-reviewed business and healthcare literature for articles about organizational performance measurement yielded 1,307 abstracts. Multi-rater relevancy ratings, citation checks, expert nominations and quality ratings resulted in 664 articles for review. Key themes were extracted from the papers, followed by multi-reader validation. Information was supplemented with grey literature.The performance literature was diverse and fragmented, and relevant evidence was difficult to locate. Most literature is non-empirical and originates from the United States and the United Kingdom. No agreement on definitions or concepts is evident within or across disciplines. Study quality is not high in either field. Performance measurement arose in public services and business at about the same time. The evolution of thought on performance measurement ranges from unfettered enthusiasm to sober reassessment.The research base on performance measurement is in its infancy, and evidence to guide practice is sparse. A coherent multidisciplinary research agenda on the topic is needed.

The ability to induce and maintain antigen-specific immunologic tolerance is the ultimate goal in allo-transplantation. Here, we report that the transplantation of unmanipulated murine pancreatic islets across the HY disparity induced transplantation tolerance that prevented HY-mismatched skin grafts being rejected.Three hundred islet equivalent of freshly isolated islets from male C57BL/6 donor mice was transplanted underneath the kidney capsule of syngeneic female recipients rendered diabetic by streptozotocin. Nephrectomy was carried out to remove the islet graft and retransplantation was performed using the contralateral kidney. For skin transplantation, donor tail skin was transplanted onto the lateral thorax.Islets from male C57BL/6 donors transplanted to syngeneic female recipients cured diabetes and the mice survived indefinitely. The acceptance of second grafts and rejection of third party islet grafts indicated antigen-specific transplantation tolerance. However, flow cytometry and ELISPOT analysis demonstrated that the HY-specific T cells were not deleted or anergized. A 2-fold increase of CD4+Foxp3+ regulatory T cells (Tregs) was observed in spleen and lymph nodes. Notably, CD25- Tregs increased threefold over levels in naïve mice. Adoptive transfer of CD4+ T cells to neonatal mice could transfer tolerance. At the graft site in long-term tolerant mice, CD4+ T cells, 40% of which were CD4+Foxp3+ Tregs (43% CD25-, 57% CD25+) infiltrated the peri-islet spaces.Unmanipulated pancreatic islets can induce immunologic tolerance associated with peripherally induced CD4+Foxp3+ Tregs, a significant proportion of which notably are CD25-.

There are many issues and potentials in the field of educational games. This chapter was developed as a collaborative blogging effort among contributing authors of this book to discuss some of the current problems and the future potentials for educational games. A variety of questions were provided in a blog format to allow an evolving discussion among the authors. Topics covered within the chapter include games and the instructional design field, problems associated with games, assessment and games, cultural implications for games in education, and future potentials for games in education.

Memory T cells are the very essence of adaptive immunity with their rapid and efficient response to antigen rechallenge and long-term persistence. However, it is becoming increasingly evident that when primed with self or transplanted tissue, these cells play a key role in causing and perpetuating tissue damage. Furthermore, current treatments, which efficiently control the naive response, have limited effects on primed T cells. We have used a treatment based on a combination of antibodies specific for molecules expressed by activated T lymphocytes to selectively remove these cells. This approach, which we termed multi-hit therapy, leads to cumulative binding of antibodies to the target T cells and a striking prolongation of skin graft survival in presensitized recipients in a stringent skin transplant model. The findings are consistent with the depletion of graft-specific CD4+ and CD8+ T cells, although other modes of action, such as T-cell regulation and altered migration could play a role. In conclusion, our therapeutic strategy controls primed T cells which are a major driving force in the pathology of many autoimmune diseases and in transplant rejection.

The history of regulatory T cells goes back to the realisation that T cells could provide ‘help’ for antibody responses: the obverse of this is their ability to hold them in check. This brief personal overview follows the initial designation of T cells as ‘suppressor’ and the various hypotheses, some now disproved, put forward for their mechanism of action. We now cautiously label them T regulatory cells, but realise they do not control not all immune regulation. They probably operate through several mechanisms, and some of these are discussed.

This paper summarizes findings of a comprehensive, systematic review of the peer-reviewed and grey literature on performance measurement according to each stage of the performance measurement process--conceptualization, selection and development, data collection, and reporting and use. It also outlines implications for practice.Six hundred sixty-four articles about organizational performance measurement from the health and business literature were reviewed after systematic searches of the literature, multi-rater relevancy ratings, citation checks and expert author nominations. Key themes were extracted and summarized from the most highly rated papers for each performance measurement stage.Despite a virtually universal consensus on the potential benefits of performance measurement, little evidence currently exists to guide practice in healthcare. Issues in conceptualizing systems include strategic alignment and scope. There are debates on the criteria for selecting measures and on the types and quality of measures. Implementation of data collection and analysis systems is complex and costly, and challenges persist in reporting results, preventing unintended effects and putting findings for improvement into action.There is a need for further development and refinement of performance measures and measurement systems, with a particular focus on strategies to ensure that performance measurement leads to healthcare improvement.

The establishment of host-versus-graft (HvG) tolerance is the primary aim of reduced intensity conditioning (RIC) regimens for allogeneic stem cell transplantation (SCT). It remains to be clarified to what extent recipient myeloablation is fundamental in the establishment of donor chimerism.We have addressed this question in a murine model of RIC SCT in which the donor-recipient combination produces HvG against the male specific minor histocompatibility antigen HY. In this system engraftment can be monitored by RT-PCR and HvG effectors enumerated by tetramer analysis.We demonstrate that the dose of irradiation influences donor hemopoietic engraftment and affects generation of anti-donor specific T cells. Chimeric recipients do not mount a HvG immune response, becoming selectively tolerant, as demonstrated by the long term acceptance of skin grafts of donor but not third party origin. However, HvG tolerance is not sufficient to secure engraftment since, even in the absence of HvG, partial myeloablation was still required. The "space" produced by myeloablation and the consequent potential for donor cell expansion could also affect HvG tolerance, since its induction is severely impaired when donor hematopoietic cells have reduced proliferative capacity.We conclude that both some degree of myeloablation and HvG tolerance are required for successful engraftment, and that the capacity of donor cells to proliferate influences the induction of HvG tolerance.

MHC class II molecules are formed from polymorphic alpha and beta chains. While pairing of chains is most efficient within class II isotypes and haplotypes, limited pairing and surface expression of mixed-haplotype and -isotype class II molecules is common. The function of such molecules in antigen presentation has been established by the unique restriction of responses in F1 mice. However, it has not been established whether mixed class II molecules are able to mediate selection of functional T cells and how the reduced avidity of the TCR/MHC interaction influences the repertoire. In this report we have addressed these issues through the production of mice expressing solely mixed-haplotype class II molecules. The mixed class II molecules promote selection of a small CD4+ T cell repertoire with modified TCR use. The selected CD4+ T cells are functional in vivo and in vitro.

The present study attempted to investigate whether women with histories of incest before 13 years of age were likely to report more dissociative symptomatology than women with their first experience of interpersonal violence in adulthood (i.e., histories of physical or sexual assault after the age of 17).

We have designed DNA fusion vaccines able to induce high levels of epitope-specific CD8+ T cells, using linked CD4+ T cell help. Such vaccines can activate effective immunity against tumor Ags. To model performance against minor histocompatibility (H) Ags important in allogeneic hemopoietic stem cell transplantation, responses against the H2Db-restricted Uty and Smcy male HY epitopes have been investigated. Vaccination of females induced high levels of tetramer-specific, IFN-γ-producing CD8+ T cells against each epitope. Vaccines incorporating a single epitope primed effector CTL able to kill male splenocytes in vitro and in vivo, and HYDbUty-specific vaccination accelerated rejection of syngeneic male skin grafts. Priming against either epitope established long-term memory, expandable by injection of male cells. Expanded CD8+ T cells remained specific for the priming HY epitope, with responses to the second suppressed. To investigate vaccine performance in a tolerized repertoire, male mice were vaccinated with the fusion constructs. Strikingly, this also generated epitope-specific IFN-γ-producing CD8+ T cells with cytotoxic function. However, numbers and avidity were lower than in vaccinated females, and vaccinated males failed to reject CFSE-labeled male splenocytes in vivo. Nevertheless, these findings indicate that DNA fusion vaccines can mobilize CD8+ T cells against endogenous minor H Ags, even from a profoundly tolerized repertoire. In the transplantation setting, vaccination of donors could prime and expand specific T cells for in vivo transfer. For patients, vaccination could activate a potentially less tolerized repertoire against similar Ags that may be overexpressed by tumor cells, for focused immune attack.

There is increasing evidence suggesting that the intrauterine environment may influence long-term bone health and the risk of developing osteoporosis in later life. Alcohol (ethanol) is one factor whose presence in the prenatal environment has long-term consequences for the offspring, including permanent growth retardation. Moreover, prenatal ethanol exposure retards both fetal and postnatal bone development. It is unknown if ethanol's effects on skeletal development result from generalized growth retardation or effects specific to skeletal development. Furthermore, the level of ethanol exposure required to produce skeletal effects is unknown. The objectives of this study were to determine (1) if ethanol exerts specific effects on fetal skeletal development that are independent from its effects on general growth, and (2) the level of prenatal ethanol exposure required to affect fetal growth and skeletal ossification. Rats were fed isocaloric diets with ethanol (15%, 25%, or 36% ethanol-derived calories (EDC), approximating low, moderate, and high exposure levels), or without ethanol (pair-fed, PF, or control, C groups), prior to and throughout 21 days of gestation. The degree of E-induced delay in development was determined by comparison of E fetuses on d21 gestation to C fetuses on d17-d21 gestation. Prenatal ethanol exposure at 36% EDC decreased fetal body weight, length, and skeletal ossification compared with PF and C fetuses on d21 gestation. Importantly, effects on ossification, but not body weight or length, were also seen at the more moderate dose of 25% EDC, and the number of bones affected and the severity of effects on ossification tended to increase with dose of ethanol. Comparison of E fetuses on d21 gestation with C fetuses from d17 to 21 gestation indicated that the ethanol-induced delay in development differed for weight and skeletal ossification, and was not uniform among skeletal sites. Taken together, these data suggest that prenatal ethanol exposure has effects on fetal skeletal development that are independent of those on overall fetal growth, and that these effects occur even at moderate levels of maternal drinking. Effects of prenatal ethanol exposure on fetal skeletal development could potentially increase the offspring's risk of osteoporosis later in life.

Background: This study examines the therapeutic effect of fluoxetine, a selective serotonin reuptake inhibitor, added to dialectical behavior therapy (DBT), an empirically supported psychosocial therapy, for the treatment of borderline personality disorder. Method: This is a 12-week, randomized, double-blind, placebo-controlled study of patients with borderline personality disorder (identified using the Structured Clinical Interview for DSM-IV Axis II Disorders). All subjects received individual and group DBT. Of the 20 subjects that completed treatment, 9 were randomly assigned to receive up to 40 mg/day of fluoxetine and 11 were randomly assigned to the placebo condition. Subjects were evaluated at baseline and at week 10 or 11 on self-report measures of depression, anxiety, anger expression, dissociation, and global functioning. The study was conducted between January 1998 and February 2000. Results: Time-by-group interaction effects revealed no significant group differences in scores from pretreatment to posttreatment on any measure. However, within the DBT/placebo group, there were significant pretreatment/posttreatment differences in the direction of improvement on all measures. No significant pretreatment/posttreatment differences were found within the DBT/fluoxetine condition. Conclusion: The data suggest that adding fluoxetine to an efficacious psychosocial treatment does not provide any additional benefits. Further studies with larger sample sizes are warranted.

Due to their ability to inhibit antigen-induced T-cell activation in vitro and in vivo, anergic T cells can be considered part of the spectrum of immunoregulatory T lymphocytes. Here we report that both murine and human anergic T cells can impair the ability of parenchymal cells (including endothelial and epithelial cells) to establish cell-cell interactions necessary to sustain leukocyte migration in vitro and tissue infiltration in vivo. The inhibition is reversible and cell-contact dependent but does not require cognate recognition of the parenchymal cells to occur. Instrumental to this effect is the increased cell surface expression and enzymatic activity of molecules such as CD26 (dipeptidyl-peptidase IV), which may act by metabolizing chemoattractants bound to the endothelial/epithelial cell surface. These results describe a previously unknown antigen-independent anti-inflammatory activity by locally generated anergic T cells and define a novel mechanism for the long-known immunoregulatory properties of these cells.

One of the factors that increases the risk of graft-versus-host disease following allogeneic stem cell transplantation is the use of multiparous females as donors. Since minor histocompatibility (H) antigens are the main targets of graft-versus-host and graft-versus-leukemia responses, we tested the hypothesis that multiparity could prime minor H antigen—specific T cells. We examined the peripheral lymphoid populations of multiparous mice and humans for evidence of priming of CD8+ T-cytotoxic lymphocytes against peptide epitopes of the male-specific minor H antigen, HY. In contrast to naive females, multiparous females have measurable levels of circulating HY-specific tetramer-positive T lymphocytes, which can be readily expanded in vitro. These findings have implications for the in vitro generation of T-cell clones as reagents for immunotherapy for tumors following stem cell transplantation. (Blood. 2003; 102:388-393)

Mesenchymal stem cells (MSCs) have been recently shown to inhibit T-cell proliferation to polyclonal stimuli. We characterized the effect of MSCs of bone marrow origin on the T-cell response of naive and memory T cells to their cognate antigenic epitopes. The immune response to murine male transplantation antigens, HY, was selected because the peptide identity and major histocompatibility complex (MHC) restriction of the immunodominant epitopes are known. C57BL/6 female mice immunized with male cells were the source of memory T cells, whereas C6 mice transgenic for HY-specific T-cell receptor provided naive T cells. Responder cells were stimulated in vitro with male spleen cells or HY peptides in the presence or absence of MSCs. MSCs inhibited HY-specific naive and memory T cells in a dose-dependent fashion and affected cell proliferation, cytotoxicity, and the number of interferon γ (IFN-γ)–producing HY peptide-specific T cells. However, the MSC inhibitory effect did not selectively target antigen-reactive T cells. When MSCs were added to the T-cell cultures in a Transwell system or MSCs were replaced by MSC culture supernatant, the inhibitory activity was abrogated. T-cell reactivity was also restored if MSCs were removed from the cultures. The expression of MHC molecules and the presence in culture of antigen-presenting cells (APCs) or of CD4+/CD25+ regulatory T cells were not required for MSCs to inhibit. We conclude that MSCs inhibit naive and memory T-cell responses to their cognate antigens. Overall our data suggest that MSCs physically hinder T cells from the contact with APCs in a noncognate fashion.

Injection of female C57BL/6 mice with immature female bone marrow-derived dendritic cells (BMDC) pulsed with a single immunodominant HY(Db) Uty peptide, WMHHNMDLI, induces prolonged survival of syngeneic male skin grafts. In contrast, injection of immature female BMDC pulsed with a single MHC class I-restricted HY(Ab) Dby peptide, NAGFNSNRANSSRSS, causes immunization similar to that following injection of male cells. Tolerance induced by HY(Db) Uty peptide pretreatment is not characterized by clonal deletion: long-term tolerant mice maintain circulating HY(Db) Uty tetramer(+) T cells which expand following exposure to male cells in vivo or in vitro. Tolerance to male skin grafts can be adoptively transferred into neonatal females with splenocytes from tolerant donors. Tolerance is specific-third-party skin grafts are rejected. We propose that tolerance in this model is initiated by cognate interaction of HY(Db) Uty-specific CD8(+) T cells with their ligand, presented either on the injected immature BMDC or on recipient DC. This interaction leads to incomplete activation of the CD8(+) T cells resulting in diminished responsiveness of CD4(+) and CD8(+) T cells specific for HY peptide epitopes subsequently presented on the male graft.

We have applied MHC class I tetramers representing the two H2b MHC class I-restricted epitopes of the mouse male-specific minor transplantation Ag, HY, to directly determine the extent of expansion and immunodominance within the CD8+ T cell compartment following exposure to male tissue. Immunization with male bone marrow (BM), spleen, dendritic cells (DCs) and by skin graft led to rapid expansion of both specificities occupying up to >20% of the CD8+ T cell pool. At a high dose, whole BM or spleen were found to be more effective at stimulating the response than BM-derived DCs. In vivo, immunodominance within the responding cell population was only observed following chronic Ag stimulation, whereas epitope immunodominance was established rapidly following in vitro restimulation. Peptide affinity for the restricting MHC molecule was greater for the immunodominant epitope, suggesting that this might be a factor in the emergence of immunodominance. Using tetramers, we were able to directly visualize the cross-primed CD8+ HY response, but we did not find it to be the principal route for MHC class I presentation. Immunization with female spleen or DCs coated with the full complement of defined HY peptides, including the Ab-restricted CD4+ Th cell determinant, failed to induce tetramer-reactive cells.

A mouse model for donor lymphocyte infusion reveals that a single immunodominant minor H antigen is responsible for the beneficial effects of donor T lymphocytes against host leukemia. Separating the good from the bad could mean the end of graft-versus-host disease in bone marrow transplants. (pages 789–794)

Objective To identify intervals containing systemic lupus erythematosus (SLE) susceptibility alleles in the BXSB strain of mice. Methods We analyzed 286 (B10 × [B10 × BXSB]F1) backcross mice for a range of phenotypic traits associated with the development of SLE in BXSB mice. The mice were genotyped using 93 microsatellite markers, and the linkage of these markers to disease was studied by extreme-phenotype and quantitative trait locus analysis. Results The disease phenotype in these backcross mice was less severe than that in BXSB mice. However, antinuclear antibody production was increased compared with the parental strain. We identified 4 areas of genetic linkage to disease on chromosome 1 (Bxs1–4), 1 on chromosome 3 (Bxs5), and another interval on chromosome 13 which were associated with various aspects of the phenotype. Bxs4 and Bxs5 are located in regions not previously linked to disease in other models of SLE. Conclusion SLE in the BXSB mouse model has a complex genetic basis and involves at least 5 distinct intervals located on chromosomes 1 and 3. There is evidence that different intervals affect particular aspects of the SLE phenotype.

This project explores the reasons that women write in diaries and blogs and the ways that they reckon with audience and identity through private writing in public spaces. It observes that women write to work through difficult experiences, to give substance to the tasks of impermanence that fill their days and lives, to forge connections with other women related to issues of mutual interest and concern, and to assert themselves as subjects of their own making in the face of competing social constructions of who they should be. The importance of this subject matter lies in the ways that writing is a source of strength to individuals who have been silenced or otherwise isolated through the circumstances of their lives. I have chosen to look at the value of writing for women, but the principles that I set forth are applicable to other groups of people, particularly those who have experienced marginalization or loss of some kind. The research traces the history of the diary and its significance for women, the evolution of the diary’s function as it has moved online, the relationship between the diary and identity formation for its writer, and finally, the relationships between writers and their audiences, particularly with the diary in its incarnation as the blog. I develop the metaphors of fig leaves and scarlet letters to represent the ways in which women negotiate the dynamics of truth, identity, and audience in textual practice and assert that emerging technologies such as the blog allow for women to move beyond the silences that these images symbolize, create communities, and give voice to their lives.

Current knowledge of histocompatibility (H) loci located outside of the major histocompatibility complex - i.e. those encoding the so-called minor H antigens - was surveyed at a recent meeting ∗ ∗The 1st International Symposium on Minor Histocompatibility Antigens was held at Bar Harbor, ME, USA, on 14–17 September 1997..

The peptide-binding properties of the nonclassical major histocompatibility complex (MHC) class 1b molecule Qa-1 were investigated using a transfected hybrid molecule composed of the alpha 1 and alpha 2 domains of Qa-1b and the alpha 3 domain of H-2Db. This allowed the use of a monoclonal antibody directed against H-2Db whilst retaining the peptide-binding groove of Qa-1b. By comparison with classical MHC class I molecules, intracellular maturation of the chimeric molecule was inefficient with weak intracellular association with beta 2-microglobulin. However, at the cell surface the hybrid molecules were stably associated with beta 2-microglobulin and were recognized by cytotoxic T lymphocyte (CTL) clones specific for the Qa-1b-presented peptide Qdm (AMAPRTLLL). A whole-cell binding assay was used to determine which residues of Qdm were important for binding to Qa-1b and CTL clones served to identify residues important for T cell recognition. Substitutions at position 1 and 5 did not reduce the efficiency of binding and had little effect on CTL recognition. In contrast, substitutions at position 9 resulted in loss of MHC class I binding. Mass spectrometric analysis of peptides eluted from immunopurified Qa-1b/Db molecules indicated that Qdm was the dominant peptide. The closely related peptide, AMVPRTLLL, which is derived from the signal sequence of H-2Dk, was also present, although it was considerably less abundant. The mass profile suggested the presence of additional peptides the majority of which consisted of eight to ten amino acid residues. Finally, the finding that a peptide derived from Klebsiella pneumoniae can bind raises the possibility that this non-classical MHC class I molecule may play a role in the presentation of peptides of microorganisms.

Systematic research on effective treatment for survivors of childhood sexual abuse with posttraumatic stress disorder (PTSD) is virtually non-existent. The aim of the present study was to compare the effectiveness of an affect-management treatment (AM) group to a wait list control condition for female survivors of childhood sexual abuse with PTSD. Forty-eight female survivors of childhood sexual abuse with PTSD were randomly assigned to either a 15-week affect-management treatment group or to a wait list control condition. All subjects received individual psychotherapy and pharmacotherapy for the duration of the study, and for at least 1-month prior to the study. Controlling for pretreatment scores, subjects who completed the affect-management treatment group (n = 17) reported significantly fewer posttreatment symptoms of PTSD and dissociation than subjects in the wait list control condition (n = 16). Our findings suggest that an affect-management group treatment is beneficial as an adjunct to individual psychotherapy and pharmacotherapy for survivors of childhood sexual abuse with PTSD.

The male-specific minor histocompatibility antigen H-Y plays an important role in both graft rejection and graft-versus-host disease following transplantation of male tissue into females that are completely matched at the major histocompatibility loci. The recent identification of two peptides that, in association with the mouse H-2Kk or human HLA B7 major histocompatibility class I molecules, are recognised by H-Y-specific T cells, has provided evidence for the molecular basis for such anti-H-Y responses. These peptides are encoded by the mouse and human homologues of a ubiquitously expressed Y chromosome gene, Smcy, whilst the equivalent peptides encoded by the X chromosome homologues of this gene fail to be recognised. Genetic studies have demonstrated that, as is the case for other minor histocompatibility antigens, peptide epitopes from several closely linked genes may be required to interact in order to elicit a response against H-Y. Definition of the peptides and the genes that encode these epitopes will allow the development of tolerogenic protocols that could specifically down-modulate the response to H-Y and perhaps even other minor histocompatibility antigens.

Objective: To assess family physician learning needs related to the care of patients with schizophrenia. Methods: Questionnaires were mailed to all family physicians and general practitioners practising in southern Alberta. Physicians were asked to indicate the number of patients with schizophrenia cared for, their interest in improving the care they provided, their preferred learning methods, and the content they wished to learn. Results: A total of 539 surveys were returned for a return rate of 43.8%. Over half of the physicians (53.5%) indicated that they saw 1 to 2 patients with schizophrenia each month. Almost half (48.5%) indicated they were somewhat or very interested in increasing the care provided. Primary learning needs included increasing their knowledge of psychopharmacologic agents and monitoring and adjusting medications. Lectures and half-day workshops were the preferred learning methods. Conclusion: Our study was helpful in identifying the types of education that physicians wanted as well as the duration of the programming prior to the development of teaching interventions.

This study examined the construct validity of the Trauma Symptom Checklist-40 (TSC-40; Elliot & Briere, 1992) in a sample of 130 female psychiatric inpatients. Consistent with other findings, the TSC-40 displayed criterion-related validity in relation to childhood sexual abuse. Survivors of sexual abuse obtained significantly higher scores than those without such a history on the overall TSC-40 and on each of the six subscales, except the Depression subscale. Convergent validity of three subscales was demonstrated, and divergent validity on the total TSC-40 and each of its subscales was established. Further, among a range of abuse-effects measures, the Sexual Abuse Trauma Index (SATI) subscale was the most powerful predictor of sexual abuse. The SATI and Dissociation subscales were the subscales most sensitive to the specific features of the sexual abuse.

This study examined the relationship between childhood sexual abuse and symptoms of a newly proposed complex posttraumatic stress disorder or disorder of extreme stress not otherwise specified (DESNOS). Compared to 34 women without histories of sexual abuse, 74 survivors of sexual abuse showed increased severity on DESNOS symptoms of somatization, dissociation, hostility, anxiety, alexithymia, social dysfunction, maladaptive schemas, self-destruction and adult victimization. In addition, a logistic regression found that a complex of symptoms representing DESNOS was significantly related to a history of sexual abuse. Consistent with other studies, the results of this study provide support for the idea that symptoms of DESNOS characterize survivors of sexual abuse.

Single amino acid disparities in MHC class I molecules can elicit transplantation responses. Since beta 2 microglobulin (beta 2m) is noncovalently associated with class I antigens on the cell membrane we investigated whether the single amino acid polymorphism at position 85 (Asp-->Ala) in the mouse beta 2m molecule can cause skin graft rejection. A B2mb transgene was introduced into CBA(B2ma) mice which subsequently expressed both forms of beta 2m. Skin from these CBA beta 2mb transgenic mice was not rejected by the parental CBA strain. Previous studies showed that cytotoxic T lymphocyte (CTL) responses directed against beta 2mb use H2Kb as a restriction element. We therefore produced mice expressing H2Kb and H2Ab as well as beta 2mb by crossing CBA.beta 2mb mice with either CBA.Kb (CBK) transgenic mice or C3H.SW mice and used these as skin graft donors for beta 2mb negative littermates. In both cases rejection of transgenic skin only occurred when mice had received both a beta 2mb graft and an H2-disparate allograft lying adjacent in the same site. Introduction of the male specific antigen, H-Y, as a helper determinant did not result in rejection of beta 2mb skin. Neither did two CTL determinants (P91A and beta 2mb) on the same graft complement one another to elicit a transplantation response. Prior immunisation with tissues expressing the beta 2m disparity alone did not generate in vivo or in vitro beta 2mb-specific CTL responses, suggesting that this single amino acid difference is not sufficient to elicit a CTL or helper T cell response.

The reason the maternal immune system does not reject a foetus may involve the downregulation of T-cell receptors specific for paternal antigens. A similar mechanism may help explain the remission seen in autoimmune patients during pregnancy.

The purpose of this study was to examine which childhood events were associated with more extensive use of adult dissociative states in 90 female inpatients with histories of sexual abuse. The study found that childhood stressors of maltreatment (physical neglect, witnessing sexual abuse, and witnessing physical abuse) were associated with higher levels of dissociative symptoms. In contrast, childhood stressors of loss (parental separation and death of a close relative) were not related to increased severity of dissociative symptoms. The study also demonstrated that a close relationship with either a parent, sibling, extraparental adult, or friend did not have a mediating effect on the degree of adult dissociative symptoms. Directions for future research are presented.

The C57BL/6 (B6) and C57BL/10 (B10) inbred mouse strains are among the most commonly used in biological research and have provided the genetic background for the construction of many congenic strains. The two substrains were derived from the parental C57BL stock and were separated prior to 1937. Since then, they have been thought to possess a very close genetic relationship. By 1992, 161 loci had been tested, and only three differed between B6 and B10: the minor histocompatibility locus H9, the immunoglobulin heavy chain locus Igh 2 on chromosome 12, and the delta-aminolevulinate dehydratase Lv locus on chromosome 4. B6 and B10 have also been shown to differ over an 8 cM segment on chromosome 4. Due to the differences at the H9 locus, B6 and B10 are not histocompatible. The aim of our study was to identify novel genetic polymorphisms between B6 and B10 mice and to analyze the BKs mouse with genetic markers such that further information can be gathered on the genetic origins of this strain. 13 refs., 3 figs.

Sitting cross-legged in a circle, the men and women train their eyes on the figure in their center. Breathless, the day itself holds still around them for a second, a half-second, waiting. And into the expectant silence the voice of the storyteller speaks; the day resumes its normal bustle, but the seated listeners only lean forward a fraction more. They would not want to miss a single word.

Immune responses against foreign tissue or organs can be directed against alloantigenic differences between donor and host encoded by genes of the major histocompatibility complex (MHC; HLA in man and H-2 in mouse). However, when MHC antigens are matched, as in HLA-identical siblings, or between different mouse strains sharing the same H-2 haplotype, graft rejection still occurs and is then directed against alloantigenic differences termed minor histocompatibility (H) antigens. Their molecular nature is not yet determined but they are recognised by T cells in an MHC-restricted manner, so are assumed to be derived from molecules co-expressed with MHC class I or II glycoproteins, possibly as peptides or as "super-antigens". The genes encoding them are scattered throughout the genome, including the Y chromosome, on which the H-Y antigen gene has been mapped in both man and mouse. One striking feature of minor H antigens is their recognition by T cells but not by antibodies. This made work with them, before our ability to generate T cell responses and maintain T cell clones in vitro, very slow but currently the use of MHC-restricted T cell clones has enabled detailed mapping studies and should eventually allow for their molecular characterisation.

The non-obese diabetic (NOD) mouse is considered to be a good model of human Type I diabetes mellitus. Both sexes develop insulitis starting at about 6 weeks of age, and onset of diabetes follows at about 30 weeks in females, but later and much less frequently in males. In some mice (but not all) infiltration of the islets leads to selective destruction of insulin-producing beta cells, which is marked by clinically overt diabetes and is thought to be an autoimmune response mediated by T cells. Both L3T4+ and Ly2+ cells have been implicated in the destructive process and we have used an in vivo transfer system, together with histological studies on the pancreas, to demonstrate the essential role played by Ly2+ T cells in the destruction of beta cells in diabetic mice.