Biomedical subjects

Hideaki Sakai

Publications and source records attributed to Hideaki Sakai.

12 recordsLinked to original sources

PubMed2006

Bioengineered chondrocyte sheets may be potentially useful for the treatment of partial thickness defects of articular cartilage.

Some treatments for full thickness defects of articular cartilage, such as cultured chondrocyte transplantation, have already been done. However, to overcome osteoarthritis, we must further study the partial thickness defect of articular cartilage. It is much more difficult to repair a partial thickness defect because few repairing cells can address such injured sites. We herein show that bioengineered layered chondrocyte sheets using temperature-responsive culture dishes may be a potentially useful treatment for partial thickness defects. We evaluated the property of these sheets using real-time PCR and histological findings, and allografted these sheets to evaluate the effect of treatment using a rabbit partial model. In conclusion, layered chondrocyte sheets were able to maintain the cartilageous phenotype, and could be attached to the sites of cartilage damage which acted as a barrier to prevent a loss of proteoglycan from these sites and to protect them from catabolic factors in the joint.

Animals↗

PubMed2006

A statistical property of multiagent learning based on Markov decision process.

We exhibit an important property called the asymptotic equipartition property (AEP) on empirical sequences in an ergodic multiagent Markov decision process (MDP). Using the AEP which facilitates the analysis of multiagent learning, we give a statistical property of multiagent learning, such as reinforcement learning (RL), near the end of the learning process. We examine the effect of the conditions among the agents on the achievement of a cooperative policy in three different cases: blind, visible, and communicable. Also, we derive a bound on the speed with which the empirical sequence converges to the best sequence in probability, so that the multiagent learning yields the best cooperative result.

Learning↗

PubMed2006

Characterization of rat cathepsin E and mutants with changed active-site residues and lacking propeptides and N-glycosylation, expressed in human embryonic kidney 293T cells.

To study the roles of the catalytic activity, propeptide, and N-glycosylation of the intracellular aspartic proteinase cathepsin E in biosynthesis, processing, and intracellular trafficking, we constructed various rat cathepsin E mutants in which active-site Asp residues were changed to Ala or which lacked propeptides and N-glycosylation. Wild-type cathepsin E expressed in human embryonic kidney 293T cells was mainly found in the LAMP-1-positive endosomal organelles, as determined by immunofluorescence microscopy. Consistently, pulse-chase analysis revealed that the initially synthesized pro-cathepsin E was processed to the mature enzyme within a 24 h chase. This process was completely inhibited by brefeldin A and bafilomycin A, indicating its transport from the endoplasmic reticulum (ER) to the endosomal acidic compartment. Mutants with Asp residues in the two active-site consensus motifs changed to Ala and lacking the propeptide (Leu23-Phe58) and the putative ER-retention sequence (Ser59-Asp98) were neither processed nor transported to the endosomal compartment. The mutant lacking the ER-retention sequence was rapidly degraded in the ER, indicating the importance of this sequence in correct folding. The single (N92Q or N324D) and double (N92Q/N324D) N-glycosylation-deficient mutants were neither processed into a mature form nor transported to the endosomal compartment, but were stably retained in the ER without degradation. These data indicate that the catalytic activity, propeptides, and N-glycosylation of this protein are all essential for its processing, maturation, and trafficking.

Alanine↗

PubMed2005

The asymptotic equipartition property in reinforcement learning and its relation to return maximization.

We discuss an important property called the asymptotic equipartition property on empirical sequences in reinforcement learning. This states that the typical set of empirical sequences has probability nearly one, that all elements in the typical set are nearly equi-probable, and that the number of elements in the typical set is an exponential function of the sum of conditional entropies if the number of time steps is sufficiently large. The sum is referred to as stochastic complexity. Using the property we elucidate the fact that the return maximization depends on two factors, the stochastic complexity and a quantity depending on the parameters of environment. Here, the return maximization means that the best sequences in terms of expected return have probability one. We also examine the sensitivity of stochastic complexity, which is a qualitative guide in tuning the parameters of action-selection strategy, and show a sufficient condition for return maximization in probability.

Algorithms↗

PubMed2005

[Analysis of mailed questionnaire for female sexual dysfunction after intra-pelvic surgery].

OBJECTIVE: Female sexual dysfunction is an unfavorable complication for women after intra-pelvic surgery. However, there has not been enough data obtained to analyze the inconvenience to female patients of intra-pelvic surgery. To clarify the categories of female sexual dysfunction after intra-pelvic surgery, we analyzed mailed questionnaires obtained from female patients who had undergone mono-therapy of intra-pelvic surgery. MATERIALS AND METHODS: A mailed questionnaire regarding female sexual dysfunction was sent to 174 patients, including 118 that had undergone a hysterectomy (Group A) and 56 ostomates (Group B) and the results were analyzed. These patients had received only intra-pelvic surgery, without radiation or chemotherapy. Of the 56 patients in Group B, 50 with rectal cancer had received a colostomy, and 6 with bladder cancer had received ileal conduits. The content of the questionnaire was as follows: age; with or without a male partner; key person for consultation in regard to sexual dysfunction; importance of sex life. Also, a before and after operation comparison was made regarding sexual frequency, sexual desire, genital response, genital transformation, dyspareunia, genital pain and itching, and orgasm. RESULTS: Seventy-eight of 174 (45%) patients returned the questionnaire. Nineteen patients without a male partner and 18 patients with a male partner had no sexual intercourse, very low sexual desire, and did not consider their sex life of importance. Twenty-five patients with a male partner (18 in Group A and 7 in Group B) had no trouble in their sexual activity after the operations. However, the other 16 patients (5 in Group A and 11 in Group B) had unsatisfactory sexual intercourse after their operations because of a decrease in sexual desire, poor genital response, and/or decrease of orgasms. Furthermore, the patients in Group B suffered significantly from sexual trouble compared with the patients in Group A. Especially, all the patients in Group B complained that their stoma prevented satisfactory sexual intercourse. CONCLUSIONS: Based on this data, we do not need to worry about female sexual dysfunction for patients without a male partner and patients with a partner but who are not sexually active before their operations. More than 60% of patients who had been sexually active before their operations maintained fair sexual activity after intra-pelvic surgery. However, we have to take care of the approximately 40% of patients who suffer from female sexual dysfunction after their operation, especially the ostomate patients.

Female↗

PubMed2004

Characteristics of the increase in plasma brain natriuretic peptide level in left ventricular systolic dysfunction, associated with muscular dystrophy in comparison with idiopathic dilated cardiomyopathy.

To determine whether the plasma brain natriuretic peptide level increases differentially in muscular dystrophy and idiopathic dilated cardiomyopathy, we investigated the plasma brain natriuretic peptide level and echocardiographic parameters in patients with similarly low left ventricular ejection fraction. The plasma brain natriuretic peptide level was lower, and the left ventricular end-diastolic diameter was shorter in the patients with muscular dystrophy than in those with idiopathic dilated cardiomyopathy. The correlation between the plasma brain natriuretic peptide and left ventricular ejection fraction was shifted downward in the patients with muscular dystrophy compared with those with idiopathic dilated cardiomyopathy. Those between the brain natriuretic peptide and left ventricular end-diastolic diameter were superimposable, although the data from the muscular dystrophy patients were located at the shorter left ventricular end-diastolic diameter side. The plasma brain natriuretic peptide level may differentially increase in the two diseases with similar left ventricular systolic dysfunction. Differences in the left ventricular distension and in the physical activity might explain at least partially the different plasma brain natriuretic peptide levels.

Adult↗

PubMed2004

A new criterion using information gain for action selection strategy in reinforcement learning.

In this paper, we regard the sequence of returns as outputs from a parametric compound source. Utilizing the fact that the coding rate of the source shows the amount of information about the return, we describe l-learning algorithms based on the predictive coding idea for estimating an expected information gain concerning future information and give a convergence proof of the information gain. Using the information gain, we propose the ratio w of return loss to information gain as a new criterion to be used in probabilistic action-selection strategies. In experimental results, we found that our w-based strategy performs well compared with the conventional Q-based strategy.

Algorithms↗

PubMed2004

Recruitment of osteoclasts in the mandible of osteopetrotic (op/op) mice.

Osteoclasts in osteopetrotic (op/op) mice are substantially reduced by the absence of functional activities of macrophage colony-stimulating factor (M-CSF). However, it is known that osteoclasts appear in op/op skeletal bones with aging, although the molecular mechanism for this is unknown. In order to investigate osteoclastic recruitment in the jaw bones of op/op mice, osteoclastic distribution was analysed for 2 yr after birth by histochemistry for tartrate-resistant acid phosphatase activity and immunohistochemistry for cathepsin K. Osteoclasts in op/op mandibular bones decreased rapidly in number after birth and disappeared by 3 d, although there was no difference in the osteoclastic distribution between op/op and normal littermates at birth. At 2 wk, osteoclasts began to reappear around op/op tooth germs, where no apparent connective tissue layer intervened between tooth germs and bone trabeculae. They increased in number and were scattered over the mandible, reaching a maximum at 8 wk, when periodontal ligament-like structures were recognizable around incisor germs. Osteoclasts then again decreased gradually, and after 62 wk few osteoclasts were seen in op/op mandibular bones, whose marrow space disappeared. These findings suggest that osteoclasts are recruited in an M-CSF-independent manner in op/op mandibles, especially in areas around tooth germs.

Acid Phosphatase↗

PubMed2004

[An outbreak of legionellosis in a nursery].

We experienced an outbreak of legionellosis in infants for the first time in Japan. In Fukushima Prefecture Wakamatsu Nursery, the patients who had respiratory symptoms of cough, wheeze and fever appeared one after another from the middle of June, 2002. We suspected that an outbreak of legionellosis had occurred and then carried out urinary antigen detection of Legionella pneumophila. As a result, 8 patients were positive. They consisted of 5 boys and 3 girls, and ranged in age from 11 months to 1 year 10 months. Underlying disease was observed in one patient, and 6 patients were hospitalized. All 8 patients had rhinorrhea, cough, fever and 7 patients had wheeze. The average duration of cough was 9.9 days and that of fever was 4.5 days. In the admitted 6 patients, WBC ranged in count from 7,500/microliter to 15,300/microliter and CRP ranged from 0.2 mg/dl to 2.5 mg/dl. Chest X-rays showed infiltrative shadows (right lower lobe, left lower lobe) in 2 patients. With regard to the treatment, macrolide or tetracycline antibiotics were administered in 4 of 8 patients, and beta-lactams were administered in others. Water samples were obtained from 12 locations at the nursery, including the shower head of the bathroom, the bathtub, the taps, the laundry and so on. But cultures of water samples failed to grow legionella. We suspected that the source of infection was the humidifiers or the nebulizer used for disinfection. Through this outbreak, it became obvious that the mild case of legionellosis really existed. Furthermore, we suggested that it was possible for the patient with mild legionellosis to cure without administration of macrolide or tetracycline antibiotics.

Disease Outbreaks↗

PubMed2003

Jaw bone remodeling at the invasion front of gingival squamous cell carcinomas.

BACKGROUND: It is still unknown how jaw bone remodeling occurs at actual invasion sites of oral squamous cell carcinomas. Since there is no other human carcinomas which make a direct invasion of the bone, gingival carcinomas are valuable examples. METHODS: Twelve surgical specimens of gingival squamous cell carcinoma were examined histopathologically and immunohistochemically for remodeling of bone and its surrounding tissue. RESULTS: Three types of bone interfaces with carcinomatous invasion were distinguished. These included areas with bone resorption, smooth bone surface and new bone formation. In the bone-resorption area, numerous osteoclasts were located along the bone surface, which was surrounded by myxoid stroma. The myxoid stroma was characterized by immunopositivity for heparan sulfate proteoglycan (HSPG), abundant vascularity and macrophagic infiltration. In the bone-formation area, rows of osteoblasts were aligned on the bone surface. The stroma around osteoblasts was also HSPG-immunopositive, poor in vascularity but rich in activated fibroblasts. In the smooth-bone area, the stroma showed an organizing phase of granulation tissue with slender fibroblasts and mature collagen fibers but with less vascularity and inflammatory infiltrates. CONCLUSION: The results indicate that the stromal architecture, especially in terms of its inflammatory cellular, vascular and matrix compositions, is strictly regulated in the timing and site of jaw bone remodeling which is causes by carcinomatous invasion.

Antigens, CD↗

PubMed2003

Disruption of structural and functional integrity of alpha 2-macroglobulin by cathepsin E.

alpha 2-Macroglobulin (alpha 2M) is an abundant glycoprotein with the intrinsic capacity for capturing diverse proteins for rapid delivery into cells. After internalization by the receptor- mediated endocytosis, alpha 2M-protein complexes were rapidly degraded in the endolysosome system. Although this is an important pathway for clearance of both alpha 2M and biological targets, little is known about the nature of alpha 2M degradation in the endolysosome system. To investigate the possible involvement of intracellular aspartic proteinases in the disruption of structural and functional integrity of alpha 2M in the endolysosome system, we examined the capacity of alpha 2M for interacting with cathepsin E and cathepsin D under acidic conditions and the nature of its degradation. alpha 2M was efficiently associated with cathepsin E under acidic conditions to form noncovalent complexes and rapidly degraded through the generation of three major proteins with apparent molecular masses of 90, 85 and 30 kDa. Parallel with this reaction, alpha 2M resulted in the rapid loss of its antiproteolytic activity. Analysis of the N-terminal amino-acid sequences of these proteins revealed that alpha 2M was selectively cleaved at the Phe811-Leu812 bond in about 100mer downstream of the bait region. In contrast, little change was observed for alpha 2M treated by cathepsin D under the same conditions. Together, the synthetic SPAFLA peptide corresponding to the Ser808-Ala813 sequence of human alpha 2M, which contains the cathepsin E-cleavage site, was selectively cleaved by cathepsin E, but not cathepsin D. These results suggest the possible involvement of cathepsin E in disruption of the structural and functional integrity of alpha 2M in the endolysosome system.

Amino Acid Sequence↗

PubMed2003

The regulation of bone resorption in tooth formation and eruption processes in mouse alveolar crest devoid of cathepsin k.

Osteoclastic bone resorption has recently been implicated in the tooth formation and eruption in alveolar bone. Cathepsin K (CK) is a cysteine proteinase expressed predominantly in osteoclasts and is believed to play a critical role in degradation of bone matrix proteins. Here we present evidence that the alveolar bone resorption is essential for the tooth formation and that eruption proceeds normally in CK-deficient (CK-/-) mice. Radiographic and histological analyses revealed that the alveolar bone from these animals had no significant abnormalities during the tooth development between 5 and 28 days after birth. The tooth crown was normally erupted through the alveolar bone layer at 28 days after birth. The number of tartrate-resistant acid phosphatase-positive multinuclear cells in the alveolar bone around the tooth germ was apparently increased in 5-day-old CK-/- mice compared with age-matched littermates. More important, however, the immunohistochemical localization of matrix metalloproteinase-9 (MMP-9) was clearly increased in the CK-/- osteoclasts. In contrast, no significant difference in the immunoreactivity for cathepsin D was observed between the CK-/- osteoclasts and the wild-type ones. These results indicate that CK-/- osteoclasts are fully differentiated and are capable of degrading the organic phase of alveolar bone during the tooth formation and eruption, which may result from the compensatory action by MMP-9 increasingly expressed in the osteoclasts.

Alveolar Bone Loss↗