Incidence of spontaneous lymphomas in non-experimental NOD/Shi-scid, IL-2Rγnull (NOG) mice.

Severely immunodeficient NOD/Shi-scid, IL-2Rγnull (NOG) mice provide an in vivo model for human cell/tissue transplantation studies. NOG mice were established by combining interleukin-2 receptor-γ chain knockout mice and NOD/Shi-scid mice. They exhibit a high incidence of thymic lymphomas and immunoglobulin (Ig) leakiness. In this study, we assessed the incidence of malignant lymphomas and the occurrence of leakiness in 2,184 non-experimental NOG retired breeder mice aged 16-40 weeks. We established that the total incidence of lymphomas was only 0.60% (13/2,184). Most lymphomas (10/13) occurred in female mice by the age of around 25 weeks. No mice developed Ig leakiness. All lymphomas were derived from the thymus, and consisted mainly of CD3-positive and CD45R-negative lymphoblastic-like cells. Therefore, based on the absence of Ig leakiness and a very low incidence of lymphomas, including thymic lymphomas, NOG mice may be useful in regeneration medicine for xenotransplantation of human embryonic stem (ES) cells or induced pluripotent stem (iPS) cells, and in transplantation experiments involving tumor cells.

An epidemiological study of the effects of statin use on airflow limitation in patients with chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is considered to be a systemic inflammatory disease, and systemic inflammation has been noted as a factor contributing to cardiovascular disease, which is one of the comorbidities associated with COPD. On the other hand, pleiotropic effects, such as the anti-inflammatory effects of statins, have attracted attention in recent years, and there have been a variety of reports regarding the usefulness of statins for patients with COPD. METHODS: We investigated whether the use or non-use of statins influenced the prevalence of airflow limitation. All outpatients who were over the age of 40 years and who regularly visited a primary health care facility were invited to participate. Each participant underwent spirometry and completed a questionnaire regarding their clinical status, which was used to screen for COPD. A variety of factors that are potentially related to airflow limitation were assessed. RESULTS: Of the 853 patients included in the study, 81 (9.5%) had airflow limitation. The prevalence of airflow limitation was 2.3% among the 89 patients with a history of statin use, which was five times lower than the prevalence of airflow limitation among patients who had not used statins (10.5%). Among the 347 patients with a history of past or current smoking, airflow limitation was not observed in the 30 patients who had used statins. However, by multivariate analysis, statin use was not significantly associated with a lower prevalence of airflow limitation. CONCLUSIONS: This is the first cross-sectional study from Japan that has demonstrated that statin use has a potential impact on airflow limitation in patients with COPD.

Overestimation of stability limits leads to a high frequency of falls in patients with Parkinson's disease.

OBJECTIVES: To test a hypothesis that patients with Parkinson's disease may not notice discrepancies between their perceived and actual stability limits and cannot keep their centre of gravity within the stability region. SETTINGS: Outpatients with neurological disorders in rehabilitation service. SUBJECTS: Twenty-one patients with Parkinson's disease (11 men, 10 women; mean duration 5.9 +/- 3.9 years) and age- and sex-matched healthy volunteers were recruited. METHODS: Each subject's right arm length was subtracted from the distance between the right acromion and the perceived reachable boundary. This was called 'perceived reach'. The figure given by subtracting the right arm length from the maximum forward reach length measured by the Functional Reach Test was named 'actual reach', and is an index of actual stability limits in each subject. The difference between actual and perceived stability limits (DAP) is given by actual reach minus perceived reach. The motor score of the Unified Parkinson's Disease Rating Scale were used to evaluate disease severity. RESULTS: The mean DAP for the Parkinson's disease group was negative (-1.8 +/- 5.7 cm) and significantly different from that of controls (3.3 +/- 9.2 cm) (P < 0.05). In Parkinson's disease, DAP was significantly correlated with the Unified Parkinson's Disease Rating Scale score (correlation coefficient = -0.39, P < 0.05). CONCLUSIONS: These results indicated that patients with Parkinson's disease overestimated their stability limits, which may result in falls. In addition, the results demonstrate that patients with Parkinson's disease develop overestimation of stability limits in parallel with their disease progression.

Stereoisomeric C5-C5'-Linked Dihydrothymine Dimers Produced by Radiolytic One-Electron Reduction of Thymine Derivatives in Anoxic Aqueous Solution: Structural Characteristics in Reference to Cyclobutane Photodimers.

Radiolytic one-electron reduction of 1-methylthymine (1a) and 1,3-dimethylthymine (1b) in anoxic aqueous solution afforded stereoisomeric C5-C5'-linked dihydrothymine dimers, fractionated into the meso forms of (5R,5'S)- and (5S,5'R)-bi-5,6-dihydrothymine (3a,b[meso]) and a racemic mixture of (5R,5'R)- and (5S,5'S)-bi-5,6-dihydrothymines (3a,b[rac]), along with 5,6-dihydrothymines (2a,b). The meso and racemic dimers were produced in almost equivalent yields, possessing structural similarity with cis-syn-cyclobutane pyrimidine photodimers that are identified as highly mutagenic and carcinogenic photolesions induced by UV light. Similar radiolytic one-electron reduction of thymidine (1c) resulted in the pseudo-meso form of (5R,5'S)- and (5S,5'R)-bi-5,6-dihydrothymidine (3c[RS]) and two diastereormers of (5R,5'R)- and (5S,5'S)-bi-5,6-dihydrothymidine (3c[RR] and 3c[SS]). X-ray crystal structures indicated that two pyrimidine rings of the stereoisomeric dimers except 3a[rac] overlap with each other to a considerable extent, as in the cis-syn-cyclobutane photodimers. The pyrimidine rings of the dimers were twisted around 5-Me-C5-C5'-5'-Me by 51.1(2)° for 3a[meso], -85.4(4)° for 3a[rac], -65(1)° for 3b[meso], 43(2)° for 3b[rac], and 64.9(4)° for 3c[RS], respectively. It was predicted that the C5-C5'-linked dihydrothymine dimers may cause some distortion within a DNA duplex if they were incorporated. The pH dependence of the reactivities was in accord with a mechanism of the C5-C5'-linked dimerization by which electron adducts of 1a-c are irreversibly protonated at C6 and the resulting 5,6-dihydrothymin-5-yl radicals undergo bimolecular coupling.