Traumatic brain injury: Age at injury influences dementia risk after TBI

Traumatic brain injury (TBI) is increasingly recognized as a risk factor for dementia. New data provide further support for this association and demonstrate the influence of age at injury and injury severity on dementia risk after TBI, revealing that even mild TBI increases dementia risk in those aged ≥65 years

Lysis mediated by T cells and restricted by H-2 antigen of target cells infected with vaccinia virus

VARIOUS virus infections lead to the formation of cytotoxic lymphocytes (CL), which are capable of killing virus-infected target cells1−4. Specific lysis of target cells infected with 51Cr-labelled vaccinia virus could be observed when investigating the cell-mediated cytotoxic reaction to vaccinia virus5; the CL could be characterised as a T cell. The sensitised lymphocytes from C3H mice could only kill syngeneic L929 cells infected with vaccinia virus, whereas lysis by sensitised lymphocytes derived from DBA/2 mice was restricted to the syngeneic infected mastocytoma P815X2 cells. In the lymphocytic choriomeningitis infection the target cell lysis was shown to be restricted by H-2 antigen6. We report here experiments with primary fibroblasts of the mouse strains C3H, DBA/2 and the (C3H DBA/2)F1 generation were designed to affirm that the effector phase of virus-specific lysis of target cells mediated by T cells is restricted by H-2 antigen even in the vaccinia virus infection. Further experiments with H-2 alloantisera were performed to indicate the close local relationship between H-2 antigens and viral surface antigens

Altered serological and cellular reactivity to H-2 antigens after target cell infection with vaccinia virus

MICE generate cytotoxic T lymphocytes (CTL) which are able to lyse virus infected target cells in vitro after infection with lymphocytic choriomeningitis virus (LCMV) and pox-viruses1−3. CTL kill syngeneic and semiallogenic infected cells but not allogenic infected targets. Target cell lysis in these systems seems to be restricted by H-2 antigens, especially by the K or D end of the major histocompatibility complex (MHC). In experiments where virus specific sensitised lymphocytes kill virus infected allogenic target cells4 the effector lymphocytes have not been characterised exactly. Recent investigations suggest that the active cell in this assay, at least in the measles infection, is a non-thymus derived cell (H. Kreth, personal communication). An H-2 restriction of cell mediated cytolysis (CMC) to trinitrophenol (TNP)-modified lymphocytes has also been described5. Zinkernagel and Doherty6 postulated that the CTL is directed against syngeneic H-2 antigens and viral antigens and they suggested an alteration of H-2 induced by the LCMV infection. Earlier7 we found a close topological relationship between H-2 antigens and the target antigen(s) responsible for CMC in the vaccinia system. Here we report experiments which were carried out to prove alteration of H-2 after infection of L-929 fibroblasts with vaccinia virus

Effective repair of articular cartilage using human pluripotent stem cell-derived tissue

In an effort to develop an effective source of clinically relevant cells and tissues for cartilage repair a directed differentiation method was used to generate articular chondrocytes and cartilage tissues from human embryonic stem cells (hESCs). It has previously been demonstrated that chondrocytes derived from hESCs retain a stable cartilage-forming phenotype following subcutaneous implantation in mice. In this report, the potential of hESC-derived articular-like cartilage to repair osteochondral defects created in the rat trochlea was evaluated. Articular cartilage-like tissues were generated from hESCs and implanted into the defects. After 6 and 12 weeks, the defects were evaluated histologically and immunohistochemically, and the quality of repair was assessed using a modified ICRS II scoring system. Following 6 and 12 weeks after implantation, hESC-derived cartilage tissues maintained their proteoglycan and type II collagen-rich matrix and scored significantly higher than control defects, which had been filled with fibrin glue alone. Implants were found to be well integrated with native host tissue at the basal and lateral surfaces, although implanted human cells and host cells remained regionally separated. A subset of implants underwent a process of remodeling similar to endochondral ossification, suggesting the potential for a single cartilaginous implant to promote the generation of new subchondral bone in addition to repair of the articular cartilage. The ability to create cartilage tissues with integrative and reparative properties from an unlimited and robust cell source represents a significant advance for cartilage repair that can be further developed in large animal models before clinicalsetting application

Trust in science, homonegativity, and HIV stigma: experimental data from the United Kingdom and Germany.

HIV stigma and its corollary HIV fear constitute significant barriers to HIV prevention. This quasi-experimental study examined social psychological predictors of HIV stigma and HIV fear, respectively, based on data from 516 participants in the United Kingdom and Germany. Participants completed baseline measures of HIV knowledge, trust in science and scientists and homonegativity. They were then randomly assigned to one of three experimental conditions with vignettes describing (1) a gay man with HIV, (2) a heterosexual man with HIV, or (3) the control condition. Participants completed post-manipulation measures of HIV stigma and HIV fear. HIV knowledge and trust in science and scientists were negatively associated with HIV stigma and fear. Baseline homonegativity was positively correlated with HIV stigma and fear. Being exposed to a vignette describing a heterosexual man led to less HIV stigma than being exposed to a vignette describing a gay man and the control condition (in which no sexual orientation was explicitly mentioned). The results suggest that, in addition to promoting HIV knowledge and trust in science and scientists, public health messaging concerning HIV should shift from a focus on gay men to heterosexuals and that homonegativity (higher in men) must continue to be tackled

CD80 on Human T Cells Is Associated With FoxP3 Expression and Supports Treg Homeostasis

CD80 and CD86 are expressed on antigen presenting cells (APCs) and their role in providing costimulation to T cells is well established. However, it has been shown that these molecules can also be expressed by T cells, but the significance of this observation remains unknown. We have investigated stimuli that control CD80 and CD86 expression on T cells and show that in APC-free conditions around 40% of activated, proliferating CD4+ T cells express either CD80, CD86 or both. Expression of CD80 and CD86 was strongly dependent upon provision of CD28 costimulation as ligands were not expressed following TCR stimulation alone. Furthermore, we observed that CD80+ T cells possessed the hallmarks of induced regulatory T cells (iTreg), expressing Foxp3 and high levels of CTLA-4 whilst proliferating less extensively. In contrast, CD86 was preferentially expressed on INF-γ producing cells, which proliferated more extensively and had characteristics of effector T cells. Finally, we demonstrated that CD80 expressed on T cells inhibits CTLA-4 function and facilitates the growth of iTreg. Together these data establish endogenous expression of CD80 and CD86 by activated T cells is not due to ligand capture by transendocytosis and highlight clear differences in their expression patterns and associated functions

The Effect of Selective Die Spacer Placement Techniques on the Seatability of Castings

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74992/1/j.1532-849X.1993.tb00382.x.pd

Cancer mortality and morbidity among plutonium workers at the Sellafield plant of British Nuclear Fuels

The mortality of all 14 319 workers employed at the Sellafield plant of British Nuclear Fuels between 1947 and 1975 was studied up to the end of 1992, and cancer incidence was examined from 1971 to 1986, in relation to their exposures to plutonium and to external radiation. The cancer mortality rate was 5% lower than that of England and Wales and 3% less than that of Cumbria. The significant excesses of deaths from cancer of the pleura and thyroid found in an earlier study persist with further follow-up (14 observed, 4.0 expected for pleura; 6 observed, 2.2 expected for thyroid). All of the deaths from pleural cancer were among radiation workers. For neither site was there a significant association between the risk of the cancer and accumulated radiation dose. There were significant deficits of deaths from cancers of mouth and pharynx, liver and gall bladder, and larynx and leukaemia when compared with the national rates. Among all radiation workers, there was a significant positive association between accumulated external radiation dose and mortality from cancers of ill-defined and secondary sites (10-year lag, P = 0.04), leukaemia (no lag, P = 0.03; 2-year lag, P = 0.05), multiple myeloma (20-year lag, P = 0.02), all lymphatic and haematopoietic cancers (20-year lag, P = 0.03) and all causes of death combined (20-year lag, P = 0.008). Among plutonium workers, there were significant excesses of deaths from cancer of the breast (6 observed, 2.6 expected) and ill-defined and secondary cancers (29 observed, 20.1 expected). No significant positive trends were observed between the risk of deaths from cancers of any specific site, or all cancers combined, and cumulative plutonium and external radiation doses. For no cancer site was there a significant excess of cancer registrations compared with rates for England and Wales. Analysis of trends in cancer incidence showed significant increases in risk with cumulative plutonium plus external radiation doses for all lymphatic and haematopoietic neoplasms for 0-, 10- and 20-year lag periods. Taken as a whole, our findings do not suggest that workers at Sellafield who have been exposed to plutonium are at an overall significantly increased risk of cancer compared with other radiation workers. © 1999 Cancer Research Campaig