Kei-ichiro Kitamura

Real-Time Monitoring of Respiration Rhythm and Pulse Rate During Sleep

A noninvasive and unconstrained real-time method to detect the respiration rhythm and pulse rate during sleep is presented. By employing the agrave trous algorithm of the wavelet transformation (WT), the respiration rhythm and pulse rate can be monitored in real-time from a pressure signal acquired with a pressure sensor placed under a pillow. The waveform for respiration rhythm detection is derived from the 26 scale approximation, while that for pulse rate detection is synthesized by combining the 24 and 25 scale details. To minimize the latency in data processing and realize the highest real-time performance, the respiration rhythm and pulse rate are estimated by using waveforms directly derived from the WT approximation and detail components without the reconstruction procedure. This method is evaluated with data collected from 13 healthy subjects. By comparing with detections from finger photoelectric plethysmograms used for pulse rate detection, the sensitivity and positive predictivity were 99.17% and 98.53%, respectively. Similarly, for respiration rhythm, compared with detections from nasal thermistor signals, results were 95.63% and 95.42%, respectively. This study suggests that the proposed method is promising to be used in a respiration rhythm and pulse rate monitor for real-time monitoring of sleep-related diseases during sleep

Unconstrained detection of respiration rhythm and pulse rate with one under-pillow sensor during sleep

A completely non-invasive and unconstrained method is proposed to detect respiration rhythm and pulse rate during sleep. By employing wavelet transformation (WT), waveforms corresponding to the respiration rhythm and pulse rate can be extracted from a pulsatile pressure signal acquired by a pressure sensor under a pillow. The respiration rhythm was obtained by an upward zero-crossing point detection algorithm from the respiration-related waveform reconstructed from the WT 26 scale approximation, and the pulse rate was estimated by a peak point detection algorithm from the pulse-related waveform reconstructed from the WT 24 and 25 scale details. The finger photo-electric plethysmogram (FPP) and nasal thermistor signals were recorded simultaneously as reference signals. The reference pulse rate and respiration rhythm were detected with the peak and upward zero-crossing point detection algorithm. This method was verified using about 24 h of data collected from 13 healthy subjects. The results showed that, compared with the reference data, the average error rates were 3.03% false negative and 1.47% false positive for pulse rate detection in the extracted pulse waveform. Similarly, 4.58% false negative and 3.07% false positive were obtained for respiration rhythm detection in the extracted respiration waveform. This study suggests that the proposed method is suitable, in sleep monitoring, for the diagnosis of sleep apnoea or sudden death syndrome.

Novel bromomelatonin derivatives suppress osteoclastic activity and increase osteoblastic activity: implications for the treatment of bone diseases.

Abstract:  The teleost scale is a calcified tissue that contains osteoclasts, osteoblasts, and bone matrix, all of which are similar to those found in mammalian membrane bone. Using the goldfish scale, we recently developed a new in vitro assay system and previously demonstrated that melatonin suppressed both osteoclastic and osteoblastic activities in this assay system. In mammals, 2‐bromomelatonin possesses a higher affinity for the melatonin receptor than does melatonin. Using a newly developed synthetic method, we synthesized 2‐bromomelatonin, 2,4,6‐tribromomelatonin and novel bromomelatonin derivatives (1‐allyl‐2,4,6‐tribromomelatonin, 1‐propargyl‐2,4,6‐tribromomelatonin, 1‐benzyl‐2,4,6‐tribromomelatonin, and 2,4,6,7‐tetrabromomelatonin) and then examined the effects of these chemicals on osteoclasts and osteoblasts. All bromomelatonin derivatives, as well as melatonin, had an inhibitory action on osteoclasts. In particular, 1‐benzyl‐2,4,6‐tribromomelatonin (benzyl‐tribromomelatonin) possessed a stronger activity than melatonin. At an in vitro concentration of 10−10 m, benzyl‐tribromomelatonin still suppressed osteoclastic activity after 6 hr of incubation. In reference to osteoblasts, all bromomelatonin derivatives had a stimulatory action, although melatonin inhibited osteoblastic activity. In addition, estrogen receptor mRNA expression (an osteoblastic marker) was increased in benzyl‐tribromomelatonin (10−7 m)‐treated scales. Taken together, the present results strongly suggest that these novel melatonin derivatives have significant potential for use as beneficial drug for bone diseases such as osteoporosis.

Unconstrained monitoring of long-term heart and breath rates during sleep

An unconstrained method for the long-term monitoring of heart and breath rates during sleep is proposed. The system includes a sensor unit and a web-based network module. The sensor unit is set beneath a pillow to pick up the pressure variations from the head induced by inhalation/exhalation movements and heart pulsation during sleep. The measured pressure signal was digitized and transferred to a remote database server via the network module. A wavelet-based algorithm was employed to detect the heart and breath rates, as well as body movement, during sleep. The overall system was utilized for a total six-month trial operation delivered to a female subject. The profiles of the heart and breath rates on a beat-by-beat and daily basis were obtained. Movements during sleep were also estimated. The results show that the daily average percentage of undetectable periods (UPs) during 881.6 sleep hours over a 180 day period was 17.2%. A total of 89.2% of sleep hours had a UP of not more than 25%. The profile of the heart rate revealed a periodic property that corresponded to the female monthly menstrual cycle. Our system shows promise as a long-term unconstrained monitor for heart and breath rates, and for other physiological parameters related to the quality of sleep and the regularity of the menstrual cycle.

Prostaglandin E2 Increases Both Osteoblastic and Osteoclastic Activity in the Scales and Participates in Calcium Metabolism in Goldfish

Using our original in vitro assay system with goldfish scales, we examined the direct effect of prostaglandin E2 (PGE2) on osteoclasts and osteoblasts in teleosts. In this assay system, we measured the activity of alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) as respective indicators of each activity in osteoblasts and osteoclasts. ALP activity in scales significantly increased following treatment at high concentration of PGE2 (10-7 and 10-6 M) over 6 hrs of incubation. At 18 hrs of incubation, ALP activity also significantly increased in the PGE2 (10-9 to 10-6 M)-treated scale. In the case of osteoclasts, TRAP activity tended to increase at 6 hrs of incubation, and then significantly increased at 18 hrs of incubation by PGE2(10-7 to 10-6 M) treatment. At 18 hrs of incubation, the mRNA expression of osteoclastic markers (TRAP and cathepsin K) and receptor activator of the NF-&kgr;B ligand (RANKL), an activating factor of osteoclasts expressed in osteoblasts, increased in PGE2 treated-scales. Thus, PGE2 acts on osteoblasts, and then increases the osteoclastic activity in the scales of goldfish as it does in the bone of mammals. In an in vivo experiment, plasma calcium levels and scale TRAP and ALP activities in the PGE2-injencted goldfish increased significantly. We conclude that, in teleosts, PGE2 activates both osteoblasts and osteoclasts and participates in calcium metabolism.

Accurate Determination of Respiratory Rhythm and Pulse Rate Using an Under-Pillow Sensor Based on Wavelet Transformation

A real-time noninvasive and unconstrained method is proposed to determine the respiratory rhythm and pulse rate with an under-pillow sensor during sleep. The sensor is composed of two fluid-filled polyvinyl tubes set in parallel and sandwiched between two acrylic plates. One end of each tube is hermetically sealed, and the other end is connected to one of two pressure sensors. Inner pressure in each tube therefore changes in accordance with respiratory motion and cardiac beating. By employing the a trous algorithm of wavelet transformation (WT), the respiratory and cardiac cycle can be discriminated from the pressure waveforms. The respiratory rhythm was obtained from the WT 26 scale approximation, and the pulse rate from the sum of WT 24 and 25 scale details without WT reconstruction after soft-threshold denoising. The algorithms latency can be set to be minimal and the respiratory rhythm and pulse rate were estimated directly from the extracted respiration and pulse waveforms, respectively. This method has been tested with a total of about 25 h data collected from 13 subjects. By comparing the detection results with those of reference data, the average pulse rate detection sensitivity and positive predictivity were 99.17% and 98.53%, and the respiratory rhythm detection sensitivity and positive predictivity were 95.63% and 95.42%

Contribution of neurons to habituation to mechanical stimulation in Caenorhabditis elegans

In Caenorhabditis elegans, a light touch induces a locomotor response. Repeated touches, however, result in an attenuation of response, that is, habituation. Withdrawal responses elicited by anterior touch are controlled by anterior mechanosensory neurons (AVM and ALMs), and by four pairs of interneurons (AVA, AVB, AVD, and PVC) (Chalfie et al., 1985; White et al., 1986). To identify the neurons that participate in habituation, we ablated these neurons with a laser microbeam and investigated the resulting habituation of the operated animals. The animals lacking both left and right homologues AVDLR were habituated more rapidly than intact animals. We propose that chemical synapses at AVD play a critical role in the habituation of intact animals.

Zebrafish scales respond differently to in vitro dynamic and static acceleration: Analysis of interaction between osteoblasts and osteoclasts

Zebrafish scales consist of bone-forming osteoblasts, bone-resorbing osteoclasts, and calcified bone matrix. To elucidate the underlying molecular mechanism of the effects induced by dynamic and static acceleration, we investigated the scale osteoblast- and osteoclast-specific marker gene expression involving osteoblast-osteoclast communication molecules. Osteoblasts express RANKL, which binds to the osteoclast surface receptor, RANK, and stimulates bone resorption. OPG, on the other hand, is secreted by osteoblast as a decoy receptor for RANKL, prevents RANKL from binding to RANK and thus prevents bone resorption. Therefore, the RANK-RANKL-OPG pathway contributes to the regulation of osteoclastogenesis by osteoblasts. Semaphorin 4D, in contrast, is expressed on osteoclasts, and binding to its receptor Plexin-B1 on osteoblasts results in suppression of bone formation. In the present study, we found that both dynamic and static acceleration at 3.0×g decreased RANKL/OPG ratio and increased osteoblast-specific functional mRNA such as alkaline phosphatase, while static acceleration increased and dynamic acceleration decreased osteoclast-specific mRNA such as cathepsin K. Static acceleration increased semaphorin 4D mRNA expression, while dynamic acceleration had no effect. The results of the present study indicated that osteoclasts have predominant control over bone metabolism via semaphorin 4D expression induced by static acceleration at 3.0×g.

Automatic sleep monitoring system for home healthcare

In this paper, we present an automatic and real-time sleep monitoring system for home healthcare. The basic system consists of sensor boards, bedside boxes and a group of servers with various functions for analyzing sleep data and reporting sleep qualities of users. The sensor board is installed beneath a pillow to measure pressure change signal during sleep. The bedside box digitizes and transmits the signal to the servers. The system is different from conventional sleep monitoring devices used in a hospital, whose sensor is non-intrusive and easy-to-use that any person can use it at home. Furthermore, it provides a web-based interactive platform for users to analyze, manage and visualize their sleep data. These functions are evaluated by dozens of persons at different age groups over three months, and they are confirmed useful not only for a doctor who is responsible for checking his/her patients daily sleep pattern, but also useful for self-care. It is of great application potential in home healthcare.

Effects of Inorganic Mercury and Methylmercury on Osteoclasts and Osteoblasts in the Scales of the Marine Teleost as a Model System of Bone

To evaluate the effects of inorganic mercury (InHg) and methylmercury (MeHg) on bone metabolism in a marine teleost, the activity of tartrate-resistant acid phosphatase (TRAP) and alkaline phosphatase (ALP) as indicators of such activity in osteoclasts and osteoblasts, respectively, were examined in scales of nibbler fish (Girella punctata). We found several lines of scales with nearly the same TRAP and ALP activity levels. Using these scales, we evaluated the influence of InHg and MeHg. TRAP activity in the scales treated with InHg (10-5 and 10-4 M) and MeHg (10-6 to 10-4 M) during 6 hrs of incubation decreased significantly. In contrast, ALP activity decreased after exposure to InHg (10-5 and 10-4 M) and MeHg (10-6 to 10-4 M) for 18 and 36 hrs, although its activity did not change after 6 hrs of incubation. As in enzyme activity 6 hrs after incubation, mRNA expression of TRAP (osteoclastic marker) decreased significantly with InHg and MeHg treatment, while that of collagen (osteoblastic marker) did not change significantly. At 6 hrs after incubation, the mRNA expression of metallothionein, which is a metal-binding protein in osteoblasts, was significantly increased following treatment with InHg or MeHg, suggesting that it may be involved in the protection of osteoblasts against mercury exposure up to 6 hrs after incubation. To our knowledge, this is the first report of the effects of mercury on osteoclasts and osteoblasts using marine teleost scale as a model system of bone.