Prediction of stroke patients' bedroom-stay duration: machine-learning approach using wearable sensor data.

Background: The importance of being physically active and avoiding staying in bed has been recognized in stroke rehabilitation. However, studies have pointed out that stroke patients admitted to rehabilitation units often spend most of their day immobile and inactive, with limited opportunities for activity outside their bedrooms. To address this issue, it is necessary to record the duration of stroke patients staying in their bedrooms, but it is impractical for medical providers to do this manually during their daily work of providing care. Although an automated approach using wearable devices and access points is more practical, implementing these access points into medical facilities is costly. However, when combined with machine learning, predicting the duration of stroke patients staying in their bedrooms is possible with reduced cost. We assessed using machine learning to estimate bedroom-stay duration using activity data recorded with wearable devices. Method: We recruited 99 stroke hemiparesis inpatients and conducted 343 measurements. Data on electrocardiograms and chest acceleration were measured using a wearable device, and the location name of the access point that detected the signal of the device was recorded. We first investigated the correlation between bedroom-stay duration measured from the access point as the objective variable and activity data measured with a wearable device and demographic information as explanatory variables. To evaluate the duration predictability, we then compared machine-learning models commonly used in medical studies. Results: We conducted 228 measurements that surpassed a 90% data-acquisition rate using Bluetooth Low Energy. Among the explanatory variables, the period spent reclining and sitting/standing were correlated with bedroom-stay duration (Spearman's rank correlation coefficient (R) of 0.56 and -0.52, p < 0.001). Interestingly, the sum of the motor and cognitive categories of the functional independence measure, clinical indicators of the abilities of stroke patients, lacked correlation. The correlation between the actual bedroom-stay duration and predicted one using machine-learning models resulted in an R of 0.72 and p < 0.001, suggesting the possibility of predicting bedroom-stay duration from activity data and demographics. Conclusion: Wearable devices, coupled with machine learning, can predict the duration of patients staying in their bedrooms. Once trained, the machine-learning model can predict without continuously tracking the actual location, enabling more cost-effective and privacy-centric future measurements.

Endovascular aneurysmal models at the external iliac artery of dogs.

INTRODUCTION: Establishing an aneurysm model using simple and easy operative techniques is desirable to develop new endovascular treatment devices such as stent grafts. We developed an aneurysm model using the external iliac arteries (EIAs) of adult Beagles, a relatively large animal that we thought would be easy to handle, using simple and less complicated endovascular procedures. In addition, we evaluated the generated aneurysm model histologically and determined the factors that were necessary for creating more dilated aneurysms. METHODS: Experimental animals consisted of 16 beagles (average weight, 14.0 kg). The animals were divided into four groups (S, E, B+S, and B+E). Eight Beagles were in the S and E groups, without balloon dilation. S group Beagles were injected with normal saline into the right EIA and served as a control group. Elastase was injected into the left EIA of the same Beagles (E group). Eight Beagles were in the B+S and B+E groups with balloon dilation. After balloon dilation, normal saline was injected into right EIA of the B+S group. Elastase was injected into the left EIA of the same Beagles (B+E). After 4 weeks, we measured the EIA diameter using abdominal ultrasound imaging from a body surface. Both sides of the EIA were harvested. We evaluated the dilation rate of the EIA diameter, and histologically, evaluated the disappearance of the internal elastic lamina, degeneration and disappearance of medial smooth muscle and the external elastic lamina, and neointimal thickening. RESULTS: Inner diameters were dilated more in the B+E group vs the other groups. The B+E group internal elastic lamina had almost disappeared, with significantly more severe degeneration and disappearance of external elastic lamina. CONCLUSIONS: We developed a muscular artery aneurysm model using the EIA arteries of adult Beagles and a simple endovascular procedure. Histologically, internal and external elastic lamina degeneration was an important factor to create significantly dilated aneurysms in this muscular artery model.

Properties of N-butyl cyanoacrylate-iodized oil mixtures for arterial embolization: in vitro and in vivo experiments.

PURPOSE: To examine the properties of N-butyl cyanoacrylate (NBCA) and iodized oil (lipiodol [Lip]) in vitro and in vivo for safe and effective embolization. MATERIALS AND METHODS: Viscosity, polymerization time, and diffusing capacity were evaluated according to the NBCA/Lip ratio in vitro. Additionally, the effect of the NBCA/Lip ratio on arterial embolization was evaluated in vivo; various ratios of NBCA/Lip were injected into the renal arteries of adult beagles, after which the embolization effect following transcatheter arterial embolization was quantitatively investigated histopathologically and using computed tomography (CT) volumetry. RESULTS: The viscosity of NBCA/Lip increased, polymerization time was prolonged, and diffusing capacity increased as the NBCA density decreased. As the NBCA density decreased, embolic material was recognized in smaller diameter arteries, and embolization of a larger vascular bed was accomplished. The NBCA/Lip mixture with a low density of NBCA was located more peripherally from the catheter tip, and embolization of more peripheral and smaller diameter arteries was achieved. CONCLUSIONS: The relationships of properties of NBCA/Lip in vitro and embolization effects in vivo of various ratios of NBCA/Lip were quantitatively examined and compared. The results of this study are useful for safe and effective embolization.

On-site Evaluation of Rehabilitation Patients Monitoring System Using Distributed Wireless Gateways.

This paper presents a hands-free monitoring system for rehabilitation patients that uses wireless gateways to fully cover the floor of an inpatient ward. For stroke rehabilitation, 24-hour monitoring is recommended. Low-power wireless such as Bluetooth Low Energy (BLE) is suitable for this purpose because of its long battery life. However, most systems require smartphones or tablet computers to acquire patient data due to BLE's short communication range. Instead of using smartphones, we installed around fifty BLE gateways to implement a hands-free data acquisition system. The system was evaluated both quantitatively and qualitatively. The data acquisition rate of the system was found to be over 90% through 24-hour patient monitoring, which is almost the same as that for systems using smartphones. Questionnaires about usability administered to both medical staff and patients suggested that they felt the smartphone-less system was more comfortable than the smartphone system. These results suggest the possibility of using such a distributed data acquisition system in real medical wards and its benefits.

Development of an enzyme-linked immunosorbent assay to detect an immunomodulatory alpha-D-glucan-protein complex, MPG-1, in basidiomycete Tricholoma matsutake and related processed foods.

We previously isolated a novel immunomodulatory alpha-(1,4)(1,6)(1,2)- d-glucan-protein complex (MPG-1) from mycelia of Tricholoma matsutake in basidiomycetes. In the present study, we raised a polyclonal antibody by immunizing rabbits with MPG-1 and constructed a sandwich enzyme-linked immunosorbent assay (ELISA) system to examine the distribution of MPG-1 among edible mushrooms and related processed foods. The system detected MPG-1 quantitatively at concentrations of more than 10 ng/mL, with a coefficient of variation of less than 10% by intra-assay and interassay precision. Analysis with the system of chemically modified MPG-1 suggested that the sugar moiety was mainly involved in the detection. The system detected MPG-1 in the extracts of the fruiting bodies of T. matsutake but not in those of 34 other basidiomycete species. Moreover, a significant amount of MPG-1 was detected in the extracts of their cultured mycelia. The antigenic structure of MPG-1 was relatively stable in terms of pH and temperature. MPG-1 was detected in processed foods supplemented with T. matsutake. These results suggest that MPG-1 is distributed predominantly in T. matsutake species and that the ELISA system can detect it in processed foods supplemented with T. matsutake.

Patient-Specific Quality Assurance Using Monte Carlo Dose Calculation and Elekta Log Files for Prostate Volumetric-Modulated Arc Therapy.

Log file-based methods are attracting increasing interest owing to their ability to validate volumetric-modulated arc therapy outputs with high resolution in the leaf and gantry positions and in delivered dose. Cross-validation of these methods for comparison with measurement-based methods using the ionization chamber/ArcCHECK-3DVH software (version 3.2.0) under the same conditions of treatment anatomy and plan enables an efficient evaluation of this method. In this study, with the purpose of cross-validation, we evaluate the accuracy of a log file-based method using Elekta log files and an X-ray voxel Monte Carlo dose calculation technique in the case of leaf misalignment during prostate volumetric-modulated arc therapy. In this study, 10 prostate volumetric-modulated arc therapy plans were used. Systematic multileaf collimator leaf positional errors (±0.4 and ±0.8 mm for each single bank) were deliberately introduced into the optimized plans. Then, the delivered 3-dimensional doses to a phantom with a certain patient anatomy were estimated by our system. These doses were compared with the ionization chamber dose and the ArcCHECK-3DVH dose. For the given phantom and patient anatomy, the estimated dose strongly coincided with the ionization chamber/ArcCHECK-3DVH dose ( P < .01). In addition, good agreement between the estimated dose and the ionization chamber/ArcCHECK-3DVH dose was observed. The dose estimation accuracy of our system, which combines Elekta log files and X-ray voxel Monte Carlo dose calculation, was evaluated.

Clinical impact of dosimetric changes for volumetric modulated arc therapy in log file-based patient dose calculations.

PURPOSE: A log file-based method cannot detect dosimetric changes due to linac component miscalibration because log files are insensitive to miscalibration. Herein, clinical impacts of dosimetric changes on a log file-based method were determined. METHODS AND MATERIALS: Five head-and-neck and five prostate plans were applied. Miscalibration-simulated log files were generated by inducing a linac component miscalibration into the log file. Miscalibration magnitudes for leaf, gantry, and collimator at the general tolerance level were ±0.5mm, ±1°, and ±1°, respectively, and at a tighter tolerance level achievable on current linac were ±0.3mm, ±0.5°, and ±0.5°, respectively. Re-calculations were performed on patient anatomy using log file data. RESULTS: Changes in tumor control probability/normal tissue complication probability from treatment planning system dose to re-calculated dose at the general tolerance level was 1.8% on planning target volume (PTV) and 2.4% on organs at risk (OARs) in both plans. These changes at the tighter tolerance level were improved to 1.0% on PTV and to 1.5% on OARs, with a statistically significant difference. CONCLUSIONS: We determined the clinical impacts of dosimetric changes on a log file-based method using a general tolerance level and a tighter tolerance level for linac miscalibration and found that a tighter tolerance level significantly improved the accuracy of the log file-based method.

Protective effect of a protein-bound polysaccharide, PSK, on CLP-induced sepsis in mice transplanted orthotopically with colon tumor.

We investigated the effects of a protein-bound polysaccharide, PSK, on the resistance of tumor-bearing mice against sepsis induced by cecal ligation and puncture (CLP). (a) In BALB/c mice that had received intracecal transplantation of colon 26 (C26) tumor, CLP with a 21-gauge needle significantly shortened the survival time, compared with that of non-tumor-bearing mice. Oral administration of PSK to such mice resulted in a significant prolongation of the survival time and increase of the survival rates. The effects were dependent on the timing of PSK administration and the dose. (b) CLP significantly increased the IL-10 level in serum, the IL-10 gene expression by spleen cells, the number of IL-10-producing CD4-positive T cells, and the productivity of IL-10 by spleen of tumor-bearing mice compared with that of non-tumor-bearing mice. PSK administration to such mice suppressed the increase. Further, PSK prevented the reduction of gene expression of IFN-gamma and the number of IFN-gamma-producing CD4-positive T cells and IFN-gamma productivity by spleen cells of tumor-bearing CLP-treated mice. (c) Treatment with anti-IFN-gamma monoclonal antibody before CLP significantly reduced the effects of PSK. These findings suggest that the protective effect of PSK on the CLP-induced sepsis in mice transplanted orthotopically with C26 tumor is possibly mediated by suppression of IL-10 and promotion of IFN-gamma.

Quantification of residual dose estimation error on log file-based patient dose calculation.

PURPOSE: The log file-based patient dose estimation includes a residual dose estimation error caused by leaf miscalibration, which cannot be reflected on the estimated dose. The purpose of this study is to determine this residual dose estimation error. METHODS AND MATERIALS: Modified log files for seven head-and-neck and prostate volumetric modulated arc therapy (VMAT) plans simulating leaf miscalibration were generated by shifting both leaf banks (systematic leaf gap errors: ±2.0, ±1.0, and ±0.5mm in opposite directions and systematic leaf shifts: ±1.0mm in the same direction) using MATLAB-based (MathWorks, Natick, MA) in-house software. The generated modified and non-modified log files were imported back into the treatment planning system and recalculated. Subsequently, the generalized equivalent uniform dose (gEUD) was quantified for the definition of the planning target volume (PTV) and organs at risks. RESULTS: For MLC leaves calibrated within ±0.5mm, the quantified residual dose estimation errors that obtained from the slope of the linear regression of gEUD changes between non- and modified log file doses per leaf gap are in head-and-neck plans 1.32±0.27% and 0.82±0.17Gy for PTV and spinal cord, respectively, and in prostate plans 1.22±0.36%, 0.95±0.14Gy, and 0.45±0.08Gy for PTV, rectum, and bladder, respectively. CONCLUSIONS: In this work, we determine the residual dose estimation errors for VMAT delivery using the log file-based patient dose calculation according to the MLC calibration accuracy.

Isolation and characterization of a novel immunomodulatory alpha-glucan-protein complex from the mycelium of Tricholoma matsutake in basidiomycetes.

Tricholoma matsutake, a high-class edible mushroom in Japan, has been reported to have excellent biological activities, but difficulty in cultivating the fruit bodies and limited bulk availability have restricted detailed studies. We have developed a method of culturing in tanks, enabling the bulk supply of the mycelia. The preparation (CM6271) exerts modulative effects on the immune competence of mice and rats. In this study, a sodium hydroxide extract of CM6271 was defatted followed by fractionation with a combination of ion exchange chromatography and gel filtration in order to identify the components involved in the expression of the activity, and a single peak fraction (MPG-1) was obtained with reversed phase chromatography. MPG-1 was a glycoprotein (sugar:protein ratio, 94.3:5.7) with a relative molecular mass of 360 kDa, and the sugar moiety contained about 90% glucose. NMR spectra and methylation analysis revealed that the alpha-1,4-linkage was the predominant glucan linkage with alpha-1,6- and alpha-1,2-linkages in the minority. The amino acid composition in the protein moiety was rich in glutamine, alanine, asparagine, leucine, glycine, valine, serine, threonine, isoleucine, and proline. MPG-1 was resistant to degradation with amylase or protease. The oral administration of MPG-1 promoted, in a dose-dependent manner, the recovery of the mouse natural killer cell activity and serum IL-12 level that had been reduced by the loading of restraint stress. The dose of MPG-1 (25 mg/kg) required for the expression of the effect decreases to 1/12 of that of CM6271 (300 mg/kg). Furthermore, MPG-1 formed a complex with TGF-beta1 in vitro, modulating the biological activity of TGF-beta1 by binding to its active form. These results indicate that the mycelium of T. matsutake contains a novel alpha-glucan-protein complex with immunomodulatory activities.

Expression and mutation of p53 gene in the lung of mice intratracheal injected with crystalline silica.

The genotoxic effect of crystalline silica (Qt) in the lung was studied to clarify that silicosis conferred a significant increase in risk subsequent lung cancer. C57BL/6N mice received a single tracheal injection of Qt at dose of 2 mg/mouse. Lung p53mRNA was suppressed significantly, but no change of p21mRNA 15 months after treatment. Mutation of p53 gene was not identified at 15 months in the Qt group. Silicotic lesions were observed in the lungs of Qt group, but silicosis with pulmonary neoplasia was no detected. These results indicated that genetic changes in the silicotic lung might lead to facilitation of carcinogenesis.

Expression of matrix metalloproteinase, tissue inhibitors of metalloproteinase and adhesion molecules in silicotic mice with lung tumor metastasis.

The number of metastatic foci in silicotic mice is approximately 1.5-fold that in normal mice and in mice treated with TiO2 as inert particles. Expression of matrix metalloproteinases (MMPs) tissue inhibitors of metalloproteinases (TIMPs) and selectins was investigated in silicotic mice with lung tumor metastasis. Expression of MMP-9 and P-selectin mRNA, but not MMP-2 and E-selectin, increased significantly, showing decreases of the ratio of expression in TIMPs/MMP-9 in tumor-bearing silicotic mice compared with the tumor-bearing normal mice and mice treated with TiO2. Pretreatment with anti-P-selectin antibody inhibited number of metastatic foci significantly in silicotic mice, while pretreatment of animals with anti MMP-9 antibody showed slight decrease of metastatic foci. This evidence indicated that up-regulation of P-selectin expression contributed to enhanced rate of tumor metastasis in lung with silicosis.

Protective effects of a protein-bound polysaccharide, PSK, against Candida albicans infection in syngeneic tumor-bearing mice via Th1 cell functions.

We investigated the effects of a protein-bound polysaccharide, PSK, on the resistance of tumor-bearing mice against Candida albicans infection. In BALB/c mice that had received subcutaneous (sc) transplantation of fibrosarcoma Meth A, viable fungal counts were increased in the kidney and the mean survival period was shortened after challenge with C. albicans, compared with healthy mice. Oral administration of PSK to such mice resulted in a significant decrease of viable fungal counts and a prolongation of the mean survival period. The ratio of CD4-positive T cells in the spleen was decreased in noninfected tumor-bearing mice and the decrease was prevented by PSK, although in vitro anticandida activities of phagocytes were not significantly affected by tumor burden or PSK. Further, intracellular interferon (IFN)-gamma productivity was enhanced and the number of IFN-gamma-producing CD4-positive T cells was enhanced by PSK. PSK enhanced the gene expression of interleukin (IL)-12 and IFN-gamma in the spleen of tumor-bearing mice inoculated with C. albicans. Treatments with anti-IL-12 or anti-IFN-gamma antibody reduced the anti-infectious effects of PSK. These findings suggest that the protective effect of PSK on sublethal inoculation with C. albicans in tumor-bearing mice is possibly mediated by Th1 cell functions.

[Effect of PSK on Th1/Th2 balance in tumor-bearing mice].

We investigated the effect of PSK on Th1/Th2 balance in tumor-bearing mice. PSK was intraperitoneally administered to Meth A-bearing BALB/c mice, and PSK caused regression of the Meth A tumor. The results of Winn assay suggested that the effect of PSK was dependent on CD4+T cells. Furthermore, spleen cells were cultured with mitomycin C-treated Meth A, after which the cytokine concentration was measured by ELISA. IFN-gamma production was increased and IL-4 showed almost no change in PSK-administered mice. In another experiment, PSK was orally administered to colon 26-bearing mice in which tumors were inoculated into the subserosal space of the cecum. Mesenteric lymph nodes cells were cultured with mitomycin C-treated colon 26 cells. IFN-gamma production was increased, but not so much as to be statistically significant, and IL-4 was significantly decreased in PSK-administered mice. PSK increased IFN-gamma and IL-12 p70 production and decreased IL-4 production when spleen cells were stimulated with Con A together with PSK in vitro. As suggested from these results, PSK might induce cytokine production that works for Th1 differentiation, and suppress cytokine production that works for Th2 differentiation, and shift the Th1/Th2 balance toward Th1 dominance in tumor-bearing mice.

The combination of 5-FU, leucovorin and CPT-11 (FOLFIRI) prolongs survival through inhibition of metastasis in an orthotopic model of colon cancer.

The aim of this study was to determine the antimetastatic efficacy of the combination of 5-fluorouracil (5-FU), leucovorin (LV), and irinotecan (CPT-11) (FOLFIRI) in an orthotopic nude mouse model of GFP-HCT-116 human colon cancer-expressing green fluorescent protein (GFP). The mice were randomly divided into four groups: Group 1: saline control; Group 2: 30 mg/kg 5-FU + 90 mg/kg LV; Group 3: 5-FU + LV + 16 mg/kg CPT-11 (FOLFIRI); and Group 4: 5-FU + LV + 24 mg/kg CPT-11. 5-FU and LV were administered on days 11, 16 and 21, and CPT-11 on days 12, 18 and 22. Survival in Groups 3 and 4 was significantly longer than that in Groups 1 and 2, although no dose-dependency on CPT-11 was observed. Analysis of the primary and metastatic tumors by GFP imaging, as well as that of oncogene expression in mesentery lymph nodes, demonstrated that tumor growth and metastasis were significantly inhibited or even prevented by FOLFIRI. Pathological evaluation also demonstrated that metastasis was also inhibited by FOLFIRI. The results of the present study suggest FOLFIRI prolongs survival by inhibiting metastasis.

Evaluation of self-expandable, FK506-coated, covered stents in canine animal model.

This study aimed to evaluate whether drug coating of the recently developed covered SENDAI stents--self-expandable stents covered with segmented polyurethane (SPU) films--reduces neointimal thickening in animal model. FK506, which is one of the most effective immunosuppressants, was used. Bare stents; non-coated, covered stents; and FK506-coated, covered stents were placed bilaterally in the external iliac arteries of beagle dogs. After 1-month observation period, angiography did not show significant stent-induced stenosis. Histological evaluation revealed a completely endothelialized intravascular lumen and the absence of thrombus formation. The area of the intimal thickening induced by the FK506-coated stents was significantly smaller than that induced by the non-coated stents, whereas it was larger in the case of both the covered stents than that in the case of the bare stent. In conclusion, FK506 treatment of the self-expandable, covered stents was confirmed to effectively inhibit intimal thickening, although the SPU film used for covering functioned as a drug carrier in addition to a scaffold for intimal formation.

Absorption and tissue distribution of an immunomodulatory alpha-D-glucan after oral administration of Tricholoma matsutake.

Alpha-D-glucan (MPG-1) separated from Tricholoma matsutake (CM6271) has been reported to show immunomodulatory activities. In this study, the plasma concentration and tissue distribution of MPG-1 after CM6271 oral administration were investigated as part of the action mechanism analysis. When CM6271 was orally administered in a single dose to mice, MPG-1 was absorbed via the intestinal tract, appeared in plasma after 16 h, was gradually excreted from the blood, and fell to background level after 48 h. The time course analysis of MPG-1 in plasma showed the following pharmacokinetic parameters of MPG-1: tmax = 24 h; Cmax = 161.1 ng/mL; AUC(0-infinity) = 2559.7 ng x h/mL. Moreover, MPG-1 was confirmed to localize in Peyer's patches, mesenteric lymph nodes (MLN), and the spleen and to promote IL-12 p70 production and NK cell activity. These results suggest that MPG-1 stimulated the intestinal immune system through Peyer's patches; moreover, it was taken into the blood and stimulated the systemic immune system.

Protein-bound polysaccharide K augments IL-2 production from murine mesenteric lymph node CD4+ T cells by modulating T cell receptor signaling.

The protein-bound polysaccharide isolated from basidiomycetes (PSK), a biological response modifier, has been used as immunotherapeutic agent for the treatment of cancers. It has been demonstrated previously that PSK activates various types of immune cells in vitro, and orally administrated PSK activates anti-tumor CD4+ T cell response in mesenteric lymph nodes (MLNs). The detailed mechanism of action of PSK, however, has not been elucidated yet. The objective of the present study was to clarify the molecular mechanism of immunopotentiating effects of PSK using primary culture of the MLN CD4+ T cells. T cell receptor (TCR) stimulation-induced interleukin-2 production from MLN CD4+ T cells was significantly augmented by PSK in a concentration-dependent manner, and the augmentation was reflected at mRNA level. Furthermore, PSK augmented transcriptional activities of nuclear factor of activated T cells and activator protein 1, and phosphorylation of extracellular signal-regulated kinase 1/2 and linker for activation of T cells induced by TCR stimulation, whereas PSK had no influences without TCR stimulation. Collectively, the results indicate that PSK augments activation of MLN CD4+ T cells, probably by modulating the TCR signaling, and provide important knowledge for the elucidation of the true target molecule(s) of PSK.

Enhanced recovery of NK cell activity in mice under restraint stress by the administration of a biological response modifier derived from the mycelia of the basidiomycete Tricholoma matsutake.

Some types of stressor act on the immune system via the network comprising the endocrine-immune-nervous systems, and are reportedly responsible for the onset of diseases as well as giving impetus to their advance. It is important for the maintenance and promotion of health to cope with stress-induced changes in immunocompetence. Therefore, we studied the effects of administration of a novel biological response modifier (CM6271) derived from the mycelia of the basidiomycete Tricholoma matsutake on the NK cell activity in mice under restraint stress, in order to evaluate its potential to modulate immune responsiveness in stress-loaded individuals. (1) When C57BL/6 mice were restrained in 50-ml tubes for more than 6 h, splenic NK cell activity decreased significantly, but recovered gradually after the mice were released. The extent of the reduction of activity and the degree of recovery depended on the duration of the restraint. (2) The oral administration of CM6271 caused a significant acceleration of the recovery of the activity. This effect was dependent on the timing of administration and the dose given. (3) The administration of CM6271 had no clear effect on the blood levels of ACTH, corticosterone or lipid peroxide levels in the liver. These findings suggest that CM6271 promotes recovery from the decrease in NK cell activity induced by restraint stress.

Inhibition of decrease in natural killer cell activity in repeatedly restraint-stressed mice by a biological response modifier derived from cultured mycelia of the basidiomycete Tricholoma matsutake.

OBJECTIVE: To develop a method to cope with stress-induced reduction in immunocompetence, we evaluated the immunomodulatory activities of a biological response modifier derived from the mycelia of the basidiomycete Tricholoma matsutake (CM6271) in mice under repeated restraint stress. METHODS: C57BL/6 mice were inserted, one per tube, into 50-ml polypropylene tubes into which more than 30 ventilation holes had been drilled, and were restrained everyday for 20 days in this fashion for set periods of time. Natural killer (NK) cell activity and NK1.1-positive cell counts in the spleen, ACTH and corticosterone levels in the blood were determined. CM6271 was orally administered daily during the restraint stress period. RESULTS: (1) When the mice were restrained in a confined space for 6 h per day for 20 days, the NK cell activity and the NK1.1-positive cell counts in the spleen significantly decreased after day 5 with an increase in the blood ACTH and corticosterone levels. (2) Oral administration of CM6271 during the restraint stress period significantly prevented the stress-induced decrease in NK cell activity. The effect was dependent on the timing, duration, and doses administered. (3) CM6271 did not significantly affect the splenic NK1.1-positive cell counts or the levels of blood ACTH and corticosterone in restraint-stressed mice. CONCLUSION: The above findings suggest that CM6271 inhibits the restraint stress-induced decrease of NK cell activity in a timing of administration and dose-dependent manner.