Delayed emergence of bovine leukemia virus after vaccination with a protective cytotoxic T cell-based vaccine

In a previous study eight MHC class I-matched sheep were vaccinated with a minimal cytotoxic T lymphocyte (CTL) peptide epitope vaccine and were challenged with the retrovirus, bovine leukemia virus (BLV). Half the vaccinated animals remained PCR negative after challenge, whereas the remaining half and the placebo group became PCR positive within 4 weeks postchallenge (Hislop AD, Good MF, Mateo L, Gardner J, Gatei MH, Daniel RCW, Meyers BV, Lavin MF, and Suhrbier A: Nat Med 1998; 4: 1193). Here we show that neither epitope mutations nor processing differences explained why half the peptide-vaccinated animals failed to resist the BLV challenge. However, in these animals the development of BLV-induced lymphosarcomas was significantly delayed compared with the placebo group, suggesting a role for CTLs in preventing retrovirus-induced cancers. Importantly, two of the initially protected animals become PCR positive after similar to1.5 years, indicating extended suppression but not elimination of challenge virus by vaccine-induced CTLs. The late emergence of virus could not be explained by epitope escape mutations or the loss of memory CTL responses. We speculate that high levels of effector CTL may be needed to protect animals from a postchallenge viremia and maintenance of such effector CTLs, rather than memory CTLs, may be required to prevent subsequent emergence of virus from latent pools.

Muscle strength and function before and after anterior cruciate ligament reconstruction using semitendonosus and gracilis

This study assessed the quadriceps and hamstring strength before and 6 months after anterior cruciate ligament (ACL) reconstructive surgery using the hamstrings and related the findings to functional performance. Six months after surgery is a critical time for assessment as this is when players are returning to sport. Maximum isokinetic strength of 31 patients with complete unilateral ACL ruptures was measured at speeds of 60 degrees and 120 degrees per second. Functional assessment included the single hop, the triple hop, the shuttle run, side-step and carioca tests. All patients underwent a controlled quadriceps emphasized home-based physiotherapy program both before and after surgery. Results show that before surgery there was a 7.3% quadriceps strength deficit at 60 degrees per second compared to the uninjured leg but no hamstring strength deficit. After surgery there was a statistically significant but relatively small loss of muscle strength. The quadriceps strength deficit had increased to 12% and there was a 10% hamstring deficit. Post-operatively there was an 11% and 6.3% improvement in the hop tests, a 9% (P < 0.01) improvement in the shuttle run, a 15% (P < 0.001) improvement in the side step and a 24% (P < 0.001) improvement in the carioca tests (P < 0.001) despite the loss of muscle strength. (C) 2001 Elsevier Science B.V. All rights reserved.

alpha-melanocyte stimulating hormone potentiates p16/CDKN2A expression in human skin after ultraviolet irradiation

The contribution of the UV component of sunlight to the development of skin cancer is widely acknowledged, although the molecular mechanisms that are disrupted by UV radiation (UVR) resulting in the loss of normal growth controls of the epidermal stem cell keratinocytes and melanocytes is still poorly understood. alpha-Melanocyte stimulating hormone (alpha-MSH), acting via its receptor MC1, has a key role in skin pigmentation and the melanizing response after exposure to UVR. The cell cycle inhibitor p16/CDKN2A also appears to have an important function in a cell cycle checkpoint response in skin after exposure to UVR. Both of these genes have been identified as risk factors in skin cancer, MC1R variants are associated with increased risk to both melanoma and nonmelanoma skin cancers, and p16/CDKN2A with increased risk of melanoma. Here we demonstrate that the increased expression of p16 after exposure to sub-erythemal doses of UVR is potentiated by alpha-MSH, a ligand for MC1R, and this effect is mimicked by cAMP, the intracellular mediator of alpha-MSH signaling via the MC1 receptor. This link between p16 and MC1R may provide a molecular basis for the increased skin cancer risk associated with MC1R polymorphisms.

Couple distress after sudden infant or perinatal death: A 30-month follow up

Objective: To examine, using a 30-month prospective study, patterns of anxiety, depression and alcohol use in couples following stillbirth, neonatal death or sudden infant death syndrome. Methodology: One hundred and thirty-eight bereaved and 156 non-bereaved couples completed standardized interviews at 2, 8, 15 and 30 months post-loss. Results: At all interviews, bereaved couples were significantly more likely than non-bereaved couples to have at least one distressed partner. Rarely were both partners distressed in either group. For bereaved couples, 'mother only' distress declined from 21% to 10% during the study. 'Father only' distress ranged from 7% to 15%, peaking at 30 months. Bereaved mothers who were distressed at 2 months reported significantly lower marital satisfaction at 30 months. Conclusions: At the couple level, the experience of a baby's death is multifaceted. Gender differences are common and partners' needs may change over time. Early recognition of these differences may facilitate longer-term adjustment for both partners.

Corticosteroid-induced glaucoma in a child after a scleral reinforcement procedure

Corticoteroid-induced glaucoma can result from either topical or systemic corticosteroid use. Compared with adults, the corticosteroid response in children is less well known. The case is reported of a child who developed glaucoma after receiving topical corticosteroids following a scleral re-inforcement procedure. The raised intraocular pressure was controlled after cessation of the corticosteroids and with the use of antiglaucoma therapy. As many forms of cortico-steroids are widely used, children on corticosteroids should have regular intraocular pressure measurements as part of their management.

Wolbachia density and virulence attenuation after transfer into a novel host

The factors that control replication rate of the intracellular bacterium Wolbachia pipientis in its insect hosts are unknown and difficult to explore, given the complex interaction of symbiont and host genotypes. Using a strain of Wolbachia that is known to over-replicate and shorten the lifespan of its Drosophila melanogaster host, we have tracked the evolution of replication control in both somatic and reproductive tissues in a novel host/Wolbachia association. After transinfection (the transfer of a Wolbachia strain into a different species) of the over-replicating Wolbachia popcorn strain from D. metanogaster to Drosophila simulans, we demonstrated that initial high densities in the ovaries were in excess of what was required for perfect maternal transmission, and were likely causing reductions in reproductive fitness. Both densities and fitness costs associated with ovary infection rapidly declined in the generations after transinfection. The early death effect in D. simulans attenuated only slightly and was comparable to that induced in D. metanogaster. This study reveals a strong host involvement in Wolbachia replication rates, the independence of density control responses in different tissues, and the strength of natural selection acting on reproductive fitness.

The measurement of actual acidity in acid sulfate soils and the determination of sulfidic acidity in suspension after peroxide oxidation

Improvements to the routine methods for the determination of actual acidity in suspension for acid sulfate soils (ASS) are introduced. The titratable sulfidic acidity (TSA) results using an improved peroxide-based method were compared with the theoretical acidity predicted by the chromium reducible sulfur method for 9 acid sulfate soils. The regression between these 2 measures of sulfidic acidity was highly significant, the slope of the regression line not significantly different from unity (P = 0.05) and the intercept not significantly different from zero. This contrasts with results of other workers using earlier peroxide oxidation methods, where TSA substantially underestimated the theoretical acidity predicted by reduced inorganic sulfur analysis. Comparison was made between the 2 principal measurements from the improved peroxide method (TSA and S-POS), with S-POS converted to theoretical sulfidic acidity to allow comparison. The relationship between these 2 measurements was highly significant. The effects of titration in suspension, as well as raising titration end points to pH 6.5, were investigated, principally with respect to the titratable actual acidity (TAA) result. TAA results obtained by KCl extraction were compared with those obtained using BaCl2, MgCl2, and water extraction. TAA in 1 M KCl suspensions titrated to pH 6.5 agreed well with titratable actual acidity measured using the 25-h extraction approach of the Lin et al. (2000a) BaCl2 method. Both BaCl2 and KCl solutions were ineffective at fully recovering acidity from synthetic jarosite without repeated extraction and titration. The application of correction factors for the estimation of total actual acidity in ASS is not supported by the results of this investigation. Acid sulfate soils that contain substantial quantities of jarosite or other acid-producing but relatively insoluble sulfate minerals continue to prove problematic to chemically analyse; however, an approach for estimating this component is discussed.