Unconstrained estimation method of delta-wave percentage included in EEG of sleeping subjects.

This paper describes an unconstrained pneumatic method of estimating the δ-wave activity of the brain from the heartbeat signal. Based on experiments showing that transinformation of the heartbeat signal corrupted by body movement was correlated with the δ-wave activity, we developed a method of estimating the percentage of the δ-wave included in the EEG from the transinformation. The comb filtering technique was used to obtain accurate transinformation. We applied the proposed method to young normal subjects to evaluate the method. As a result, the correlation between the δ -wave included in the EEG and the transinformation was 0.727 and the average error of the estimates of δ-wave percentage was 14.9%. The δ-wave activity and heartbeat activity were shown to be quantitatively related. This suggests that sleep depth can be estimated from the δ -wave percentage estimated by unconstrained measurement of the heartbeat signal of young normal subjects.

Novel humanized anti-CD20 monoclonal antibodies with unique germline VH and VL gene recruitment and potent effector functions.

The anti-CD20 chimeric monoclonal antibody (mAb) rituximab is the most widely used therapeutic antibody for B-cell malignancies. However, approximately 50% of non-Hodgkin's lymphoma (B-NHL) patients respond to treatment with this antibody. Novel humanized antibodies target membrane CD20 with enhanced effector properties should improve treatment for a broader patient population with relapsed and refractory disease. A novel chimerized form of the murine anti-CD20 1K1791 exerts more potent antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) activities and induces cell death by a non-caspase dependent process. Humanized mAbs derived from 1K1791 were designed using four different humanization techniques and characterized. In contrast to rituximab or 2F2 (human anti-CD20 mAb), several of these exhibited superior ADCC, CDC, inhibition of cell growth and cell death. There was a wide range of functional differences among the humanized forms of 1K1791 despite a modest replacement of amino acid residues in the CDRs. To determine whether the superior activities exhibited by parental murine mAb 1K1791 were due to differences in VH and VL rearrangement, we analyzed its germline and compared it to other anti-CD20 mAbs. A remarkable conservation of VH and Vk (VL kappa) gene usage was observed in the murine anti-CD20 mAbs. 18/23 used the same germline gene J558.42 and 4/23 used closely related genes of the 'J558' group. Thus, 22/23 belonged to VH1 family. One exception was the mAb 1K1791, which was derived from the VH9.12 germline gene. 1K1791 was also unique in its use of a Vk19/28 family gene whereas most other mAbs (21/23) used Vk4/5 family genes. A formal relationship between the particular germline gene recruitment and antibody functionality has not been established, however, the present findings identified humanized mAbs with functional activities that were superior to rituximab and 2F2. These in vitro results support future in vivo animal testing and subsequent clinical trials.

Successful guidance by automatic output of music and verbal messages for daily behavioural disturbances of three individuals with dementia.

There have been no previous reports of daily home activities of individuals with dementia being guided by the combination of music and verbal messages. This study evaluated the effectiveness for three individuals of music and messages which were automatically output by an IC recorder. After music was presented, messages instructed the participants to go to a day care centre, behave more peacefully and eat more at meals, respectively. These stimuli were highly effective for guiding the above activities. This study suggests that automatic output of music and messages has potential as a strategy for guiding individuals with dementia at their home. For the third individual, the music and messages were output through a doll. The implications of using a doll are also discussed.

Cytokine profile in colonic mucosa of ulcerative colitis correlates with disease activity and response to granulocytapheresis.

OBJECTIVE: The aim of this study was to clarify the correlation between cytokine profile in colonic mucosa with disease activity and response to granulocytapheresis (GCAP) in patients with ulcerative colitis (UC), using a reliable, reproducible quantitative method. METHODS: Colonoscopic biopsies of inflamed colonic mucosa (16 patients, 21 cases) and uninflamed colonic mucosa (25 patients, 33 cases) were obtained from UC patients. Messenger (m)RNA was extracted and subjected to realtime polymerase chain reaction for quantitative measurement of interleukin (IL)-12, interferon-gamma, tumor necrosis factor-alpha, IL-4, IL-8, and IL-18 mRNAs. In seven patients with high disease activity despite prednisolone (PSL) treatment (> or = 20 mg/day), one course of GCAP was conducted, and pre- and post-GCAP cytokine profiles were determined. RESULTS: In inflamed colonic mucosa of UC patients, three cytokine profiles were observed: 1) high expression of interferon-gamma, tumor necrosis factor-alpha, and IL-4 mRNAs but low expression of IL-8 mRNA; 2) high expression of IL-8 mRNA and low expression of others; and 3) low expression of all cytokines examined. Inflamed colonic mucosa of patients with high disease activity showed the second pattern. Inflamed colonic mucosa of patients who were not treated with PSL and who had low disease activity showed the first pattern, whereas those on high-dose PSL exhibited the second pattern. IL-8 mRNA was significantly higher in inflamed UC samples than in uninflamed samples. GCAP was effective in five of seven PSL-resistant patients (71.4%). IL-8 was the only cytokine that correlated with effectiveness of GCAP. Compared with GCAP nonresponders, responders had significantly higher IL-8 mRNA before GCAP and showed marked reduction of IL-8 mRNA after GCAP. CONCLUSIONS: IL-8 mRNA was significantly increased in inflamed mucosa of UC. Patients with high IL-8 mRNA expression in colonic mucosa despite PSL treatment were responsive to GCAP. Therefore, quantitative measurement of mucosal IL-8 mRNA may be useful in predicting the response to GCAP.