Stem cells ameliorate EAE via an indoleamine 2,3-dioxygenase (IDO) mechanism

Syngeneic, pluripotent Lin(-)Sca1(+) bone marrow stem cells (SC), transferred to mice with experimental autoimmune encephalomyelitis, a model of multiple sclerosis, enhanced recovery, prevented relapses and promoted myelin repair. SC-treated mice showed elevated interferon-gamma production and induction of indoleamine 2,3-dioxygenase (IDO) in CD11c(+) dendritic cells (DC). IDO induction was specific since in the presence of IDO-producing CD11c(+) DC, PLP stimulated T cell proliferation was inhibited and the IDO-inhibitor, 1-MT, abrogated the SC effect. Relapse prevention during chronic disease correlated with decreased responsiveness to PLP(178-191) and MBP(85-99). Thus, pluripotent SC induce IDO in DC leading to inhibition of antigen reactivity and spreading in EAE.     

Relationship between low ultraviolet B irradiance and higher breast cancer risk in 107 countries

Abstract:  Epidemiological data show an inverse relationship between vitamin D levels and breast cancer incidence. This study investigates the relationship of modeled and measured serum 25-hydroxyvitamin D [25(OH)D] levels with age-standardized incidence rates of breast cancer in 107 countries. The hypothesis being tested is that breast cancer incidence is inversely related to geographically-dependent cutaneous sunlight exposure. A multiple regression approach was used to examine the contributions of ultraviolet B (UVB) irradiance to age-standardized incidence rates of breast cancer in the 107 countries with data on these covariates—total column ozone thickness, per capita intake of alcohol and energy from animal and vegetable sources, cigarettes, proportion of female population overweight, and total fertility. Age-standardized incidence rates were substantially higher at latitudes distant from the equator ( R ²  = 0.43, p   <   0.0001). The dose–response gradient between modeled serum 25(OH)D levels and incidence rates of breast cancer followed a standard inverse dose–response curve. Increasing increments in serum 25(OH)D in the range above 22 ng/mL were associated with incrementally lower incidence rates of breast cancer. According to multiple regression, UVB irradiance adjusted for cloud cover was inversely associated with incidence rates (p   =   0.04) after controlling for covariates. Intake of energy from animal sources was also positively associated with incidence rates (p   <   0.01). The overall coefficient of determination, R ², was 0.81 (p   <   0.0001). There was a protective effect of UVB irradiance on risk of breast cancer that was independent of fertility rate, proportion of the population overweight, alcohol intake, animal energy intake, and other covariates.     

The research priorities of patients attending UK cancer treatment centres: findings from a modified nominal group study

Members of the public are increasingly consulted over health care and research priorities. Patient involvement in determining cancer research priorities, however, has remained underdeveloped. This paper presents the findings of the first consultation to be conducted with UK cancer patients concerning research priorities. The study adopted a participatory approach using a collaborative model that sought joint ownership of the study with people affected by cancer. An exploratory, qualitative approach was used. Consultation groups were the main method, combining focus group and nominal group techniques. Seventeen groups were held with a total of 105 patients broadly representative of the UK cancer population. Fifteen areas for research were identified. Top priority areas included the impact cancer has on life, how to live with cancer and related support issues; risk factors and causes of cancer; early detection and prevention. Although biological and treatment related aspects of science were identified as important, patients rated the management of practical, social and emotional issues as a higher priority. There is a mismatch between the research priorities identified by participants and the current UK research portfolio. Current research activity should be broadened to reflect the priorities of people affected by the disease.     

The Cotton osteotomy: indications and techniques

Stage II posterior tibial tendon dysfunction (PTTD) is characterized by an incompetent posterior tibial tendon that results in a flexible pes planovalgus deformity. As the hindfoot drifts into valgus, compensatory varus develops in the forefoot. Alternatively, in some cases medial column instability can result in primary forefoot varus that drives the hindfoot into valgus. Recently, there has been increasing awareness of the importance of forefoot varus in PTTD.     

Serial adoptive transfer of murine experimental allergic encephalomyelitis: successful transfer is dependent on active disease in the donor

In an attempt to understand the mechanisms underlying disease progression in adoptively transferred experimental allergic encephalomyelitis (EAE), and perhaps multiple sclerosis (MS), this study has examined the transfer of EAE serially from primary to secondary and tertiary recipients using myelin basic protein (MBP)-responsive lymphocytes. It was found that EAE could be serially transferred only when there was acute or relapsing disease activity in the donor animal. Cells from donors with quiescent disease did not transfer EAE. Autoradiographic attempts to locate primary adoptively transferred cells in the central nervous system of secondary and tertiary recipients were uniformly unsuccessful. These findings implicate the requirement of effector cell activation in the donor and the recruitment of augmenting autoimmune cells in lesion formation.