Exploring the factors associated with decreased dynamic balance ability in older patients with heart failure.

BACKGROUND: Older patients with heart failure (HF) have a higher prevalence of frailty and poorer dynamic balance ability than other community-dwelling older adults. However, the association of frailty and other clinical characteristics with dynamic balance ability in these patients remains unclear. OBJECTIVES: We aimed to determine the clinical characteristics associated with decreased dynamic balance ability in older patients with HF. METHODS: This observational study included patients aged ≥65 years who could walk independently and were admitted to our university hospitals to undergo a cardiac rehabilitation. The timed up and go test (TUG) was used to evaluate dynamic balance ability. Pearson's and Spearman's correlation analyses were performed to determine the relationships between TUG scores and clinical characteristics. A multiple regression model based on the forced entry method was used to determine independent predictors of TUG scores. RESULTS: Of the 183 participants in this study (94 women; mean age, 82.5 ± 8.1 years), 116 (61.7%) had frailty. Pearson's and Spearman's correlation analyses revealed that age, frailty, sex, knee extensor muscle strength, maximum calf circumference, and Mini-Mental State Examination-Japanese version (MMSE-J) score were significantly correlated with TUG score (p < 0.001). Further, multiple regression analysis showed that age (p < 0.001), frailty (p = 0.041), knee extensor muscle strength (p = 0.002), and MMSE-J score (p = 0.048) were independent predictors of TUG scores. CONCLUSION: Multiple factors, including age, frailty, knee extensor muscle weakness, and cognitive function impairment are independently associated with decreased dynamic balance ability in older patients with HF.

Poor walking ability outcome and activities of daily living improvement in patients undergoing cardiac rehabilitation during COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has had wide-ranging impacts across international healthcare systems and direct impacts on rehabilitation professionals. Few outcome data for cardiac patients undergoing rehabilitation programs during the COVID-19 pandemic are available. AIM: We conducted a study to compare the effect of modified rehabilitation therapies mainly performed in wards versus conventional therapies mainly performed in rehabilitation units in which exercise on a treadmill and cardiopulmonary exercise testing were available. DESIGN: Observational study. SETTING: University hospital. POPULATION: Fifty-five consecutive inpatients admitted to a university hospital and underwent a cardiac rehabilitation program from August 2019 to June 2020. METHODS: The patients were divided into two groups: those admitted during the COVID-19 outbreak (Group A, N.=28) and those admitted before the COVID-19 outbreak (Group B, N.=27). The evaluation included age, sex, duration of the rehabilitation intervention program, days before initiation of the rehabilitation program, functional status, and Functional Independence Measure (FIM) Score. RESULTS: A higher proportion of patients in Group A than B underwent a cardiac rehabilitation program provided in wards (88.5% vs. 48.8%, respectively). Group A showed a significantly lower 6-minute walking distance and walking speed than Group B at discharge (P=0.031 and 0.014, respectively). Group A showed a significantly shorter exercise time using an ergometer than Group B (P=0.028). CONCLUSIONS: The difference in the cardiac rehabilitation location during the COVID-19 pandemic may affect the rehabilitation contents and lead to less improvement in physical function. CLINICAL REHABILITATION IMPACT: A cardiac rehabilitation program was performed mainly in wards instead of in rehabilitation units during the COVID-19 pandemic. Walking abilities were adversely affected by the modified cardiac rehabilitation program.

Effect of ankle joint fixation on tibialis anterior muscle activity during split-belt treadmill walking in healthy subjects: A pilot study.

OBJECTIVES: This study aims to examine the characteristics of muscle activity change of the tibialis anterior (TA) muscle in healthy adults while they walked on a split-belt treadmill with one fixed ankle. PATIENTS AND METHODS: This randomized controlled trial was conducted between November 2017 and July 2018. Fourteen healthy male individuals (mean age 31.4 years; range, 23 to 50 years) were divided into two groups: right ankle joint fixed by ankle-foot orthosis (fixation group) and no orthosis (control group). Both groups were asked to walk on a treadmill with the same belt speed. After familiarizing with walking on both belts at 5.0 km/h, they walked for 6 min with the right belt slower (2.5 km/h) and the left faster (5.0 km/h). For analysis, the 6 min were divided equally among three time periods. The TA muscle activity was calculated at first and last time periods. We compared muscle activities in time periods (early and late phase) and in groups (fixation and control) using two-way mixed analysis of variance. RESULTS: The TA muscle activity decreased in the late phase regardless of ankle joint fixation, and also decreased in the fixation group regardless of the time periods. There was an interaction between these factors. CONCLUSION: These data show that changes in the TA muscle activity were smaller in the fixation group, suggesting that the ankle joint fixation reduces the adaptation.

Effect of Manual Upper Eyelid Elevation on Intraocular Pressure Measurement by Four Different Tonometers.

SIGNIFICANCE: This study is the first to show that the manual upper eyelid elevation (manual UEE) that is commonly used to prevent disruption of the IOP measurement due to blinking or upper eyelid contact with the tip of the tonometer does not affect the IOP values. PURPOSE: We investigated whether manual UEE affects the IOP readings using three rebound tonometers (Icare TA01i, Icare PRO, and Icare ic100) and Goldmann applanation tonometry (GAT). METHODS: One eye was measured for 101 patients (56 eyes of primary open-angle glaucoma patients and 45 healthy subjects). The IOPs were measured without and with manual UEE. Each IOP was measured twice; the measurement order using the tonometers was randomly selected. In addition, palpebral fissure height (distance between the upper and lower eyelids) was measured. RESULTS: The IOPs without manual UEE were 12.1 ± 2.9, 13.3 ± 2.7, 11.7 ± 2.9, and 16.0 ± 3.2 mmHg (Icare TA01i, Icare PRO, Icare ic100, and GAT), and those with manual UEE were 12.3 ± 3.0, 13.3 ± 2.8, 11.7 ± 2.9, and 16.0 ± 3.3, respectively. No significant difference was found between the IOP without and with manual UEE (IOP difference; all, P > .50; paired t test). Multiple linear regression analyses revealed that palpebral fissure height did not affect IOP difference for any of the tonometers. CONCLUSIONS: Simple manual UEE when measuring the IOP has little effect on the IOP obtained using all current rebound tonometers and GAT.

Predictive impact of early mobilization on rehospitalization for elderly Japanese heart failure patients.

The aim of this study was to determine whether early mobilization was associated with rehospitalization among elderly heart failure patients. We measured the time from admission to mobilization and other clinical characteristics for 190 heart failure patients (mean age, 80.7 years). The primary outcome was heart failure rehospitalization. Kaplan-Meier survival curves were plotted and the hazard ratios for rehospitalization were determined using Cox proportional hazards regression models. During a median follow-up period of 750 days, 58 patients underwent rehospitalization. The time from admission to mobilization was significantly longer for these patients than for those who were not rehospitalized. Univariate and multivariate Cox proportional hazards analyses showed that the time from admission to mobilization was an independent predictor of rehospitalization, and receiver-operating characteristic analysis determined an optimal cutoff value of 3 days for differentiating the patients more likely to experience a subsequent cardiac event (sensitivity, 76%; specificity, 69%; area under the curve, 0.667). Kaplan-Meier survival curve analysis showed a significantly lower event rate in the ≤ 3-day group (p = 0.001, log-rank test). In conclusion, the time from admission to mobilization may be one of the strongest predictors of rehospitalization in elderly heart failure patients. Early mobilization within 3 days may be an initial target for the acute phase treatment of heart failure.

The difference in determinant factor of six-minute walking distance between sarcopenic and non-sarcopenic elderly patients with heart failure.

BACKGROUND: The purpose of this study was to identify the factors determining exercise capacity in elderly patients with heart failure (HF) with and without sarcopenia. METHODS: We studied 186 consecutive patients with HF who met the criteria of being >60 years, with no physical disability. During hospitalization, we measured the 6-min walking distance (6MWD) and other physical functional parameters and evaluated echocardiographic and laboratory measurements indicating the severity of HF. First, we divided patients into two groups (the sarcopenia group and the nonsarcopenia group) according to the presence of sarcopenia defined as fulfilling more than or equal to two criteria-body mass index <18.5, walking speed <0.8m/s, and grip strength <26kg in males, or <18kg in females. Then the association between the 6MWD and the clinical variables mentioned above was analyzed by univariate and multiple logistic regression analyses. RESULTS: The sarcopenia group comprised 77 patients (41.2%). In univariate analysis, age, grip strength, walking speed, and knee extensor muscle strength were significantly correlated with the 6MWD (p<0.05), whereas other clinical parameters were not. In multivariate analysis, walking speed was selected as an independent factor determining the 6MWD in both groups; however, knee extensor muscle strength was selected as an independent factor determining the 6MWD only in the sarcopenia group. CONCLUSION: We demonstrated that knee extensor muscle strength was an independent factor determining exercise capacity-especially in elderly patients with HF with sarcopenia, and provided useful information in terms of exercise prescription.

Comparison of the Intraocular Pressure Measured Using the New Rebound Tonometer Icare ic100 and Icare TA01i or Goldmann Applanation Tonometer.

PURPOSE: We evaluated the agreement between the intraocular pressure (IOP) values of new rebound tonometer, Icare ic100, and Icare TA01i or Goldmann applanation tonometer (GAT). METHODS: We studied one eye each of 106 subjects (57 with primary open-angle glaucoma, 49 healthy subjects). IOP was randomly measured twice with the patient in sitting position using the Icare ic100, Icare TA01i, and GAT. Tonometer measurements were evaluated using Bland-Altman analysis. The relationship between IOP difference (Icare ic100-GAT) and age, sex, disease, axial length, central corneal thickness (CCT), and corneal curvature was investigated using multivariate regression analysis. RESULTS: IOPs measured using Icare ic100, Icare TA01i, and GAT were 11.7±3.0 (mean±standard deviation), 12.2±2.9, and 16.0±3.2 mm Hg, respectively (P<0.001, one-way analysis of variance). Icare ic100 showed significantly lower IOPs than GAT (P<0.05), but not than Icare TA01 (P>0.05; Tukey-Kramer test). Bland-Altman analysis revealed that the mean differences between Icare ic100 and Icare TA01i and those between Icare ic100 and GAT were -0.46 and -4.2 mm Hg, respectively (95% limits of agreement, -3.35 to 2.42 and -10.10 to 1.61 mm Hg, respectively). For IOP differences between Icare ic100 and GAT, parameters selected in the optimal model were CCT (coefficient, 20.3, P=0.029), corneal curvature (3.0, P=0.020), and glaucoma-normal (-1.0, P=0.004). CONCLUSIONS: The new rebound tonometer Icare ic100 almost constantly showed IOPs lower than GAT. The difference was affected by CCT, corneal curvature, and disease.

[A Case of Kanji Agraphia Resulting from Intracerebral Hemorrhage on the Left Temporal Lobe Associated with Multiple Dural Arteriovenous Fistulas].

A 60-year-old, right-handed man suffered from mild word finding difficulties and kanji agraphia. Brain computed tomography revealed left temporal lobe hemorrhage, and cerebral angiogram revealed multiple dural arteriovenous fistulas (d-AVFs) in the left anterior cranial fossa and middle cranial fossa. Surgical shunt ablation was performed, and the lesions were obliterated completely. Analysis of the kanji agraphia during neuropsychological rehabilitation showed similar symptoms to those of the left posterior inferior temporal lobe lesion. Re-evaluation of magnetic resonance imaging showed multiple microbleeds on the left inferior temporal lobe, which could be responsible for the kanji agraphia. In this case, analysis of clinical symptoms with careful neuropsychological examination was important for understanding these pathologies. (Received March 21, 2017; Accepted June 21, 2017; Published December 1, 2017).

A Pilot Evaluation Assessing the Ease of Use and Accuracy of the New Self/Home-Tonometer IcareHOME in Healthy Young Subjects.

PURPOSE: We investigated the ease of use and accuracy of a new self/home-tonometer (IcareHOME) versus Goldmann applanation tonometry (GAT) and the Icare tonometer (Icare) by measuring the diurnal intraocular pressure (IOP). PATIENTS AND METHODS: The right eyes of 43 healthy young subjects were studied. The IOP was measured using the IcareHOME, GAT, and Icare 6 times a day, every 2 hours, from 8:00 to 18:00. The coincidence of the diurnal curves among all tonometers was analyzed using a linear mixed model. The intradevice and interdevice agreement was evaluated using the intraclass correlation coefficients (ICC) and Bland-Altman method. The subjects' perception of the IcareHOME was evaluated using a questionnaire. RESULTS: The liner mixed model showed similar diurnal IOP curves for all tonometers (P=0.543); however, significant differences were observed between the tonometers over time (P<0.001). The intradevice repeatability was ICC>0.8 among all tonometers, although the interdevice agreement was lowest between the IcareHOME and GAT (ICC=0.641). The IOP values were significantly lower for the IcareHOME than for the GAT at 12:00, 16:00, and 18:00 (P<0.05, Tukey-Kramer test). The mean differences between the Icare and IcareHOME and GAT and IcareHOME were 0.83 and 1.03 mm Hg, respectively (95% limit of agreement: -4.17 to 5.84 mm Hg and -3.91 to 5.98 mm Hg, respectively). Regarding the subjects' perception of handling the IcareHOME, 17 (39.5%) subjects answered "easy to use," 20 (46.5%) answered "normal," and six (13.9%) answered "difficult to use." CONCLUSIONS: The IcareHOME can be used as a self/home-tonometer; however, it may result in lower IOP values.

Intradevice and Interdevice Agreement Between a Rebound Tonometer, Icare PRO, and the Tonopen XL and Kowa Hand-held Applanation Tonometer When Used in the Sitting and Supine Position.

PURPOSE: The aim of the study was to investigate the agreement between a new portable tonometer, Icare PRO, and the Tonopen XL and Kowa hand-held applanation tonometers (HAT). METHODS: The right eyes of 127 healthy subjects were enrolled. Intraocular pressure (IOP) was measured in both sitting and supine positions using the Icare PRO, Tonopen XL, and Kowa HAT tonometers. The repeatability of the IOP measurements was evaluated by calculating intraclass correlation coefficients. Between-method agreements of tonometer measurements were evaluated using Bland-Altman analysis. RESULTS: Intradevice agreement: The intraclass correlation coefficients (sitting, supine) of Icare PRO, Tonopen XL, and Kowa HAT were (0.863, 0.656), (0.845, 0.819), and (0.957, 0.956), respectively.Interdevice agreement: The Bland-Altman analysis revealed that, in the sitting position, the mean differences between Icare PRO and Tonopen XL, and between Icare PRO and Kowa HAT were -0.43 and 0.43 mm Hg, respectively (95% limits of agreement: -6.24 to 5.34 mm Hg, -4.04 to 4.90 mm Hg). In the supine position, the corresponding mean differences were -0.88 and 0.14 mm Hg (95% limits of agreement: -5.66 to 3.91 mm Hg, -4.06 to 4.33 mm Hg). IOP differences between Icare PRO and the other tonometers were unaffected by central corneal thickness. CONCLUSIONS: The repeatability of Icare PRO was slightly lower in the supine position than in the sitting position. Although Icare PRO underestimated IOP values in eyes with higher IOP when compared with Tonopen XL and Kowa HAT in both positions, we observed good interdevice agreement between Icare PRO and both Tonopen XL and Kowa HAT.

Intraocular pressure of supine patients using four portable tonometers.

PURPOSE: To evaluate the congruity of intraocular pressure (IOP) measurements from supine patients, which were obtained using four portable tonometers. METHODS: Intraocular pressure measurements were obtained from the right eye of 72 supine patients. We used the iCare (Tiolat Oy, Helsinki, Finland) rebound tonometer, the Diaton (BICOM Inc., Long Beach, NY) transpalpebral tonometer, the Tonopen XL (Reichert inc., Depew, NY), and a Kowa hand-held applanation tonometer (HAT; Kowa Company, Ltd., Nagoya, Japan). Relationships between mean IOPs were evaluated using Pearson correlation coefficients, and the mean differences between tonometers, using one-way analysis of variance followed by Tukey-Kramer post-hoc analysis. Levels of agreement were evaluated using Bland-Altman analysis. RESULTS: The mean IOPs (mean ± SD) were 18.2 ± 3.5 mm Hg for iCare, 14.8 ± 3.4 mm Hg for Diaton, 16.7 ± 3.7 mm Hg for Tonopen XL, and 16.8 ± 2.8 mm Hg for Kowa HAT. Pearson correlation coefficients between iCare, Tonopen XL, and Kowa HAT ranged from 0.382 to 0.577, whereas those between Diaton and other tonometers ranged from 0.041 to 0.286. Post-hoc analysis indicated significant differences between all pairs except Tonopen XL and Kowa HAT. The mean difference between measurements from iCare and Diaton was 3.39 ± 3.39 mm Hg; iCare and Tonopen XL, 1.47 ± 3.52 mm Hg; iCare and Kowa HAT, 1.49 ± 2.90 mm Hg; Diaton and Tonopen XL, -1.93 ± 4.90 mm Hg; Diaton and Kowa HAT, -1.90 ± 4.15 mm Hg; and Tonopen XL and Kowa HAT, 0.02 ± 3.61 mm Hg. Computation of the width of the 95% limits of agreement resulted in a wide bias range when comparing Diaton with all tonometers. Relatively good agreements were observed between iCare, Tonopen XL, and HAT. CONCLUSIONS: Intraocular pressure measurements obtained in a supine position by four portable tonometers were not interchangeable. Although iCare and Tonopen XL significantly overestimated IOP values in eyes with a higher IOP when compared with Kowa HAT, the agreements between iCare, Tonopen XL, and Kowa HAT were at clinically acceptable levels.

Comparison of anterior chamber depth measurements by 3-dimensional optical coherence tomography, partial coherence interferometry biometry, Scheimpflug rotating camera imaging, and ultrasound biomicroscopy.

PURPOSE: To evaluate the congruity of anterior chamber depth (ACD) measurements using 4 devices. SETTING: Saneikai Tsukazaki Hospital, Himeji City, Japan. DESIGN: Comparative case series. METHODS: In 1 eye of 42 healthy participants, the ACD was measured by 3-dimensional corneal and anterior segment optical coherence tomography (CAS-OCT), partial coherence interferometry (PCI), Scheimpflug imaging, and ultrasound biomicroscopy (UBM). The differences between the measurements were evaluated by 2-way analysis of variance and post hoc analysis. Agreement between the measurements was evaluated using Bland-Altman analysis. To evaluate the true ACD using PCI, the automatically calculated ACD minus the central corneal thickness measured by CAS-OCT was defined as PCI true. Two ACD measurements were also taken with CAS-OCT. RESULTS: The mean ACD was 3.72 mm ± 0.23 (SD) (PCI), 3.18 ± 0.23 mm (PCI true), 3.24 ± 0.25 mm (Scheimpflug), 3.03 ± 0.25 mm (UBM), 3.14 ± 0.24 mm (CAS-OCT auto), and 3.12 ± 0.24 mm (CAS-OCT manual). A significant difference was observed between PCI biometry, Scheimpflug imaging, and UBM measurements and the other methods. Post hoc analysis showed no significant differences between PCI true and CAS-OCT auto or between CAS-OCT auto and CAS-OCT manual. Strong correlations were observed between all measurements; however, Bland-Altman analysis showed good agreement only between PCI true and Scheimpflug imaging and between CAS-OCT auto and CAS OCT manual. CONCLUSION: The ACD measurements obtained from PCI biometry, Scheimpflug imaging, CAS-OCT, and UBM were significantly different and not interchangeable except for PCI true and CAS-OCT auto and CAS-OCT auto and CAS-OCT manual. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Purification of N-acetyllactosamine-binding activity from the porcine sperm membrane: possible involvement of an ADAM complex in the carbohydrate-binding activity of sperm.

Although the importance of carbohydrate recognition by sperm during egg zona pellucida binding has been widely reported, the sperm molecular species that recognize the carbohydrates are poorly characterized. Our previous cytochemical study indicated that two kinds of carbohydrate-binding proteins are expressed on porcine sperm heads-one recognizes N-acetyllactosamine (Galß1-4GlcNAc-), and the other recognizes the Lewis X structure (Galß1-4(Fucα1-3)GlcNAc-). For this report, we used proteomic techniques to characterize the sperm proteins that bind N-acetyllactosamine. Porcine sperm plasma membrane was solubilized with a detergent solution and subjected to sequential chromatography with dextran sulfate agarose, affinity, and hydroxyapatite, and the binding activities in the eluates were monitored by a solid-phase binding assay. The tryptic peptides of two proteins most likely associated with the binding activities were subjected to tandem mass spectrometry sequencing. A subsequent database search identified one of the two proteins as predicted disintegrin and metalloprotease domain-containing protein 20-like (XP_003128672). The other protein was identified as disintegrin and metalloprotease domain-containing protein 5 (AB613817) by database searches for homologous amino acid sequences, cDNA cloning, nucleotide sequencing and nucleotide database searches. Furthermore, two-dimensional blue native/SDS-PAGE demonstrated that they formed a variety of non-covalent complexes. Therefore, these ADAM complexes probably are responsible for the N-acetyllactosamine-binding activity. An affinity-purified fraction containing these ADAM complexes showed zona pellucida-binding activity, though the activity was relatively weak, and the presence of another zona pellucida-binding protein that probably works in concert with these ADAM complexes was suggested. Immunofluorescence testing suggested that ADAM20-like was localized on the anterior part of the sperm plasma membrane.

Effects of anticipation certainty on preparatory brain activity and anticipatory postural adjustments associated with voluntary unilateral arm movement while standing.

We examined the effects of anticipation certainty concerning which voluntary movement is required in response to a stimulus while standing on preparatory brain activity and anticipatory postural adjustments (APAs). Ten right-handed adults abducted their left or right arm rapidly in response to a visual imperative stimulus, based on the type of stimulus. A warning cue, which did or did not contain information about the side of arm abduction, was presented 2000ms before the imperative stimulus. Preparatory brain activity before arm abduction was quantified by the mean amplitude of the contingent negative variation 100ms before the imperative stimulus (late CNV amplitude). Compared with the low anticipation condition, in the high anticipation condition the following results were obtained only in the case of right arm abduction: (1) larger late CNV amplitude, (2) earlier postural muscle activities with respect to the focal muscle of arm abduction, and (3) smaller peak displacement of center of pressure during the abduction. These findings suggest that high anticipation of voluntary movement of dominant arm to a stimulus while standing influences preparatory brain activity before the movement, resulting in earlier APAs and thus smaller disturbance of postural equilibrium during the movement.

Deficits in task-specific modulation of anticipatory postural adjustments in individuals with spastic diplegic cerebral palsy.

We examined whether individuals with spastic diplegic cerebral palsy (SDCP) have the ability to utilize lower leg muscles in anticipatory postural adjustments (APAs) associated with voluntary arm movement while standing, as well as the ability to modulate APAs with changes in the degree of postural perturbation caused by arm movement. Seven individuals with spastic diplegia (SDCP group, 12-22 yr of age) and seven age- and sex-matched individuals without disability (control group) participated in this study. Participants flexed both shoulders and lifted a load under two different load conditions, during which electromyographic activities of focal and postural muscles were recorded. Although the timing of anticipatory activation of the erector spinae and medial hamstring (MH) muscles was similar in the two participant groups, that of the gastrocnemius (GcM) muscle was significantly later in the SDCP group than in the control group. An increase in anticipatory postural muscle activity with an increase in load was observed in MH and GcM in the control group but not in GcM in the SDCP group. The degree of modulation in MH was significantly smaller in the SDCP group than in the control group. An additional experiment confirmed that these differences in APAs between the two participant groups were unlikely to be attributable to their differences in initial standing posture before load lift. The present findings suggest that lower leg muscles play a minor role in APAs in individuals with spastic diplegia. In addition, it is likely that these individuals have difficulty modulating anticipatory postural muscle activity with changes in the degree of postural perturbation.

Therapeutic effects of novel anti-tumor reagent, apoptosis inducing nucleosides from CD57+HLA-DRbright natural suppressor cell line on human gastric carcinoma-bearing SCID mice.

To further provide scientific evidence before clinical application, the anti-tumor effects of apoptosis inducing nucleosides (AINs) released from CD57+HLA-DRbright natural suppressor (CD57.DR-NS) cell line on human gastric carcinoma (GCIY)-bearing severe combined immunodeficiency (SCID) mice were examined by monitoring tumor cell growth and change of body weight of mice. The results obtained evidenced that AINs strongly induced apoptosis in the tumor tissues in SCID mice with decrease of tumor size and without loss of body weight. We found that peak 5 and peak 6 (P5 and P6) components among six components (AINs) isolated from CD57.DR-NS cell cultures by high performance liquid chromatography (HPLC) are the most effective. The anti-tumor effective dosage of P5, P6 and their mixture, P5+P6, were obtained in dose-dependent manner. Thus, the most effective method of administration of AINs for tumor regression without exhaustion was established in the present study. Corresponding to the previous study that AINs could generate apoptosis in malignant cells while lacking the toxicity in normal cells, the results obtained in the present preclinical experiments suggested anti-tumor efficacy of AINs with possible refrainment from side-effects in clinical trials.

Effects of apoptosis-inducing nucleosides released from CD57+HLA-DRbright natural suppressor cell line on human breast cancer cell death and growth.

The CD57+HLA-DRbright-natural suppressor (57.DR-NS) cell line induced apoptosis in estrogen-non-responsive human breast carcinoma MDA-MB-435 cells by apoptosis-inducing nucleosides (AINs) released into the cultures. We obtained six active AINs isolated by high performance liquid chromatography (HPLC) from 57.DR-NS cell cultures. Each AIN isolated from 57.DR-NS cell cultures induced apoptosis in MDA-MB-435 cells. We found the occurrence of DNA strand breaks followed by the activation of caspase-3 during AIN-induced apoptosis in MDA-MB-435 cells. The data obtained here indicated that 57.DR-NS cells could induce apoptosis in MDA-MB-435 cells mediated by AINs through DNA strand breaks and activation of caspase-3. Furthermore, the administration of AINs into MDA-MB-435 tumor-bearing SCID mice culminated in strong suppression of tumor growth with no change of body weight of experimental mice suggesting no side effects of AINs.

Induction of apoptosis mediated by fas receptor and activation of caspase-3 in MRL-+/+ or MRL-lpr/lpr murine oocytes.

The molecular mechanisms leading to ovarian follicular atresia in the typical pathways of programmed cell death remain to be clarified. Here we have demonstrated that the apoptotic signalling pathway in MRL-+/+ (MRL/+) murine oocytes is through the Fas receptor followed by the activation of caspase-3. In contrast, we found that the aberrant expression and dysfunction of the mutant Fas receptor in MRL-lpr/lpr (MRL/lpr) murine oocytes caused by insertion of the early transposable element (ETn) into the Fas gene were associated with an inability to activate the caspase cascade (especially caspase-3) and to induce nuclear DNA fragmentation. These findings indicate that the induction of apoptosis in MRL/lpr murine oocytes did not occur in the presence of a defective Fas receptor lacking the death domain to trigger the caspase cascade, suggesting a failure to induce ovarian follicular atresia.