Infusion of select leukemia-reactive TCR Vbeta+ T cells provides graft-versus-leukemia responses with minimization of graft-versus-host disease following murine hematopoietic stem cell transplantation

AbstractT-cell receptor (TCR) Vbeta-expression analysis by complementarity-determining region 3 (CDR3)-size spectratyping can identify the reactive populations in an immunologic response. This analysis was used in this study to characterize the Vbeta responses of C57BL/6 (B6) CD4+ and CD8+ T cells directed to either alloantigen (against [B6xDBA/2]F1; anti-H2d) or the syngeneic myeloid leukemia MMB3.19. Vbeta families exhibiting reactivity to the leukemia cells were then enriched for and administered in both syngeneic and allogeneic hematopoietic stem cell transplantation (HSCT) models to assess in vivo graft-versus-leukemia (GVL) potential. In syngeneic transplants, enrichment for pools of selected Vbeta families (Vbeta7, -11, and -13) of T cells or for a single Vbeta family (Vbeta7) of CD4+ T cells conveyed a beneficial GVL response to the recipients. Furthermore, in the haploidentical allogeneic model, both Vbeta6,7-enriched donor B6 T cells and Vbeta7-enriched CD4+ T cells exhibited significant GVL responses with concomitant minimization of graft-versus-host disease (GVHD) development compared with equal numbers of unfractionated T cells. These results suggest that CDR3-size spectratype analysis of and subsequent selection from donor T-cell repertoires can be an effective approach to separate GVL and GVHD potential following allogeneic HSCT.Biol Blood Marrow Transplant 2001;7(4):187-96

Reviews

Poems and Stories. J.R.R. Tolkien, illustrated by Pauline Baynes. Reviewed by Nancy-Lou Patterson. Tolkien\u27s Art. Jane Chance Nitzsche. Reviewed by Nancy-Lou Patterson. Dorothy L, Sayers: Nine Literary Studies. Trevor H. Hall. Reviewed by Nancy-Lou Patterson. C.S. Lewis. Spinner of Tales. Evan K. Gibson. Reviewed by Sister Mary Anthony Weinig. J.R.R. Tolkien. Fantasy Literature als Wunscherfulling und Weltdeutung. Dieter Petzold. Reviewed by Manfred Zimmerman. The Language of the Night: Essays on Fantasy and Science Fiction. Ursula Le Guin, edited and with introduction by Susan Wood. Reviewed by Grace E. Funk

The Effects of Creatine Monohydrate Loading on Exercise Recovery in Active Women throughout the Menstrual Cycle

Creatine supplementation improves anaerobic performance and recovery; however, to date, these outcomes have not been well explored in females. This study evaluated the effect of creatine monohydrate loading on exercise recovery, measured by heart rate variability (HRV) and repeated sprint performance, in women across the menstrual cycle. In this randomized, double-blind, cross-over study, 39 women (mean ± standard deviation: age: 24.6 ± 5.9 years, height: 172.5 ± 42.3 cm, weight: 65.1 ± 8.1 kg, BF: 27.4 ± 5.8%) were randomized to a creatine monohydrate (n = 19; 20 g per day in 4 × 5 g doses) or non-caloric PL group (n = 20). HRV was measured at rest and after participants completed a repeated sprint cycling test (10 × 6 s maximal sprints). Measurements were conducted before and after supplementation in the follicular/low hormone and luteal/high hormone phases. Creatine monohydrate supplementation did not influence HRV values, as no significant differences were seen in HRV values at rest or postexercise. For repeated sprint outcomes, there was a significant phase × supplement interaction (p = 0.048) for fatigue index, with the greatest improvement seen in high hormone in the creatine monohydrate group (−5.8 ± 19.0%) compared to changes in the PL group (0.1 ± 8.1%). Sprint performance and recovery were reduced by the high hormone for both groups. Though not statistically significant, the data suggests that creatine monohydrate could help counteract performance decrements caused by the high hormone. This data can help inform creatine monohydrate loading strategies for females, demonstrating potential benefits in the high hormone phase

Cancer incidence and mortality in 23 000 patients with type 1 diabetes in the UK : long‐term follow‐up

Type 2 diabetes is associated with raised risk of several cancers, but for type 1 diabetes risk data are fewer and inconsistent We assembled a cohort of 23 473 UK patients with insulin‐treated diabetes diagnosed at ages <30, almost all of whom will have had type 1 diabetes, and for comparison 5058 diagnosed at ages 30 to 49, of whom we estimate two‐thirds will have had type 2, and followed them for an average of 30 years for cancer incidence and mortality compared with general population rates. Patients aged <30 at diabetes diagnosis had significantly raised risks only for ovarian (standardised incidence ratio = 1.58; 95% confidence interval 1.16‐2.11; P < .01) and vulval (3.55; 1.94‐5.96; P < .001) cancers, with greatest risk when diabetes was diagnosed at ages 10‐14. Risks of cancer overall (0.89; 0.84‐0.95; P < .001) and sites including lung and larynx were significantly diminished. Patients diagnosed with diabetes at ages 30 to 49 had significantly raised risks of liver (1.76;1.08‐2.72) and kidney (1.46;1.03‐2.00) cancers, and reduced risk of cancer overall (0.89; 0.84‐0.95). The raised ovarian and vulval cancer risks in patients with type 1 diabetes, especially with diabetes diagnosed around pubertal ages, suggest possible susceptibility of these organs at puberty to metabolic disruption at diabetes onset. Reduced risk of cancer overall, particularly smoking and alcohol‐related sites, might reflect adoption of a healthy lifestyle

Decadal changes in fire frequencies shift tree communities and functional traits

Global change has resulted in chronic shifts in fire regimes. Variability in the sensitivity of tree communities to multi-decadal changes in fire regimes is critical to anticipating shifts in ecosystem structure and function, yet remains poorly understood. Here, we address the overall effects of fire on tree communities and the factors controlling their sensitivity in 29 sites that experienced multi-decadal alterations in fire frequencies in savanna and forest ecosystems across tropical and temperate regions. Fire had a strong overall effect on tree communities, with an average fire frequency (one fire every three years) reducing stem density by 48% and basal area by 53% after 50 years, relative to unburned plots. The largest changes occurred in savanna ecosystems and in sites with strong wet seasons or strong dry seasons, pointing to fire characteristics and species composition as important. Analyses of functional traits highlighted the impact of fire-driven changes in soil nutrients because frequent burning favoured trees with low biomass nitrogen and phosphorus content, and with more efficient nitrogen acquisition through ectomycorrhizal symbioses. Taken together, the response of trees to altered fire frequencies depends both on climatic and vegetation determinants of fire behaviour and tree growth, and the coupling between fire-driven nutrient losses and plant traits

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Temporal mapping of photochemical reactions and molecular excited states with carbon specificity

Photochemical reactions are essential to a large number of important industrial and biological processes. A method for monitoring photochemical reaction kinetics and the dynamics of molecular excitations with spatial resolution within the active molecule would allow a rigorous exploration of the pathway and mechanism of photophysical and photochemical processes. Here we demonstrate that laser-excited muon pump-probe spin spectroscopy (photo-μSR) can temporally and spatially map these processes with a spatial resolution at the single-carbon level in a molecule with a pentacene backbone. The observed time-dependent light-induced changes of an avoided level crossing resonance demonstrate that the photochemical reactivity of a specific carbon atom is modified as a result of the presence of the excited state wavefunction. This demonstrates the sensitivity and potential of this technique in probing molecular excitations and photochemistry