Human T-cell leukemia virus type 1 (HTLV-1) infection of mice: proliferation of cell clones with integrated HTLV-1 provirus in lymphoid organs

Human T-cell leukemia virus type 1 (HTLV-1) is suggested to cause adult T-cell leukemia after 40 to 50 years of latency in a small percentage of carriers. However, little is known about the pathophysiology of the latent period and the reservoir organs where polyclonal proliferation of cells harboring integrated provirus occurs. The availability of animal models would be useful to analyze the latent period of HTLV-1 infection. At 18 months after HTLV-1 infection of C3H/HeJ mice inoculated with the MT-2 cell line, which is an HTLV-1-producing human T-cell line, HTLV-1 provirus was detected in spleen DNA from eight of nine mice. No more than around 100 proviruses were found per 10(5) spleen cells. Cellular sequences flanking the 3' long terminal repeat (LTR) and the clonalities of the cells which harbor integrated HTLV-1 provirus were analyzed by linker-mediated PCR. The results showed that the flanking sequences are of mouse genome origin and that polyclonal proliferation of the spleen cells harboring integrated HTLV-1 provirus had occurred in three mice. A sequence flanking the 5' LTR was isolated from one of the mice and revealed the presence of a 6-nucleotide duplication of cellular sequences, consistent with typical retroviral integration. Moreover, PCR was performed on DNA from infected tissues, with LTR primers and primers derived from seven novel flanking sequences of the three mice. Data revealed that the expected PCR products were found from lymphatic tissues of the same mouse, suggesting that the lymphatic tissues were the reservoir organs for the infected and proliferating cell clones. The mouse model described here should be useful for analysis of the carrier state of HTLV-1 infection in humans.     

Newly developed waist actigraphy and its sleep/wake scoring algorithm

The purpose of this study was to formulate an algorithm for assessing sleep/waking from activity intensities measured with a waist-worn actigraphy, the Lifecorder PLUS (LC; Suzuken Co. Ltd., Nagoya, Japan), and to test the validity of the algorithm. The study consisted of 31 healthy subjects (M/F = 20/11, mean age 31.7 years) who underwent one night of simultaneous measurement of activity intensity by LC and polysomnography (PSG). A sleep(S)/wake(W) scoring algorithm based on a linear model was determined through discriminant analysis of activity intensities measured by LC over a total of 235 h and 56 min and the corresponding PSG-based S/W data. The formulated S/W scoring algorithm was then used to score S/W during the monitoring epochs (2 min each, 7078 epochs in total) for each subject. The mean agreement rate with the corresponding PSG-based S/W data was 86.9%, with a mean sensitivity (sleep detection) of 89.4% and mean specificity (wakefulness detection) of 58.2%. The agreement rates for the individual stages of sleep were 60.6% for Stage 1, 89.3% for Stage 2, 99.2% for Stage 3 + 4, and 90.1% for Stage REM. These results demonstrate that sleep/wake activity in young to middle-aged healthy subjects can be assessed with a reliability comparable to that of conventional actigraphy through LC waist actigraphy and the optimal S/W scoring algorithm.