An intrinsically semi-permeable PDMS nanosheet encapsulating adipose tissue-derived stem cells for enhanced angiogenesis.

Cell encapsulation devices are expected to be promising tools that can control the release of therapeutic proteins secreted from transplanted cells. The protein permeability of the device membrane is important because it allows the isolation of transplanted cells while enabling the effectiveness of the device. In this study, we investigated free-standing polymeric ultra-thin films (nanosheets) as an intrinsically semi-permeable membrane made from polydimethylsiloxane (PDMS). The PDMS nanosheet with a thickness of 600 nm showed intrinsic protein permeability, and the device fabricated with the PDMS nanosheet showed that VEGF secreted from implanted adipose tissue-derived stem cells (ASCs) could be released for at least 5 days. The ASC encapsulation device promoted angiogenesis and the development of granulation tissue 1 week after transplantation to the subcutaneous area of a mouse. This cell encapsulation device consisting of PDMS nanosheets provides a new method for pre-vascularization of the subcutaneous area in cell transplantation therapy.

One-colour control of activation, excitation and deactivation of a fluorescent diarylethene derivative in super-resolution microscopy.

We demonstrated one-colour control of activation, excitation and deactivation of a fluorescent diarylethene derivative by using a 532 nm CW laser at a weak output power. This one-colour control method was applied to single-molecule tracking in polymer films over a total duration of a few hours at room temperature and PALM for the nanostructures of polymer systems.

Optimization of X-ray microplanar beam radiation therapy for deep-seated tumors by a simulation study.

A Monte Carlo simulation was applied to study the energy dependence on the transverse dose distribution of microplanar beam radiation therapy (MRT) for deep-seated tumors. The distribution was found to be the peak (in-beam) dose and the decay from the edge of the beam down to the valley. The area below the same valley dose level (valley region) was decreased with the increase in the energy of X-rays at the same beam separation. To optimize the MRT, we made the following two assumptions: the therapeutic gain may be attributed to the efficient recovery of normal tissue caused by the beam separation; and a key factor for the efficient recovery of normal tissue depends on the area size of the valley region. Based on these assumptions and the results of the simulated dose distribution, we concluded that the optimum X-ray energy was in the range of 100-300 keV depending on the effective peak dose to the target tumors and/or tolerable surface dose. In addition, we proposed parameters to be studied for the optimization of MRT to deep-seated tumors.

Hybrid ameloblastoma and adenomatoid odontogenic tumor: report of a case and review of hybrid variations in the literature.

Hybrid odontogenic tumors including 2 or more different histologic types have been documented, but their occurrences are not very common. We present a case of hybrid odontogenic tumor composed of ameloblastoma and adenomatoid odontogenic tumor (AOT) arising in the mandibular molar region of a 31-year-old Japanese woman who had a history of familial adenomatous polyposis. The tumor, measuring 10 mm in diameter, was surgically removed from the alveolar bone. Histopathologically, the tumor consisted of both follicular and plexiform types of ameloblastoma in which multiple and smaller foci of AOT were intermingled. There have been 3 reported cases of hybrid ameloblastoma and AOT, all of which presented unicystic types as ameloblastoma components. This, however, is the first report of a hybrid tumor containing an authentic solid-type ameloblastoma compartment and an AOT compartment in a patient with a background of familial adenomatous polyposis.

Tetraspanin gene expression levels as potential biomarkers for malignancy of gingival squamous cell carcinoma.

Accurate assessment of malignancy in oral squamous cell carcinoma is essential to optimize treatment planning. To detect a biomarker related to malignant propensity in gingival squamous cell carcinoma (GSCC), quantitative gene expression analysis of tetraspanin family genes was conducted. In 73 cases of GSCC, total RNA was extracted from carcinoma tissues, and gene expression was analyzed by quantitative real time-PCR. Six tetraspanin family genes (CD9, CD63, CD81, CD82, CD151, NAG-2) were investigated. Housekeeping genes (ACTB and GAPDH), anchor protein genes (JUP and PXN) and an integrin gene (ITGA3) were used as reference genes. Forty-five gene expression ratios were calculated from these 11 gene expression levels and were analyzed with clinical parameters using multivariate statistical methods. According to the results of the logistic regression analysis subjecting cervical lymph node metastasis as a target variable, CD9/ACTB (p = 0.013) or CD9/CD82 (p = 0.013) in addition to tumor size (p = 0.028) were detected as significant factors. In Cox proportional hazards regression analysis, delayed cervical lymph node metastasis (p = 0.039) and tumor cell positive surgical margin (p = 0.032) in addition to CD151/GAPDH (p = 0.024) were detected as significant factors for death outcome. A Kaplan-Meier survival curve presented a significantly lower survival rate of the group with a CD151/GAPDH value of 10 or more (log rank and generalized Wilcoxon tests: p = 0.0003). Results of this study present the usefulness of CD9 and CD151 expression levels as biomarkers for assessment of malignancy in GSCC. They also indicate that detection of residual tumor cells at the surgical margin and the biological malignancy of a tumor interdependently affects prognosis.

The 2G allele of promoter region of matrix metalloproteinase-1 as an essential pre-condition for the early onset of oral squamous cell carcinoma.

BACKGROUND: Matrix metalloproteinase (MMP) is known to be involved in the initial and progressive stages of cancer development, and in the aggressive phenotypes of cancer. This study examines the association of single nucleotide polymorphisms in promoter regions of MMP-1 and MMP-3 with susceptibility to oral squamous cell carcinoma (OSCC). METHODS: We compared 170 Japanese OSCC cases and 164 healthy controls for genotypes of MMP-1 and MMP-3. RESULTS: The frequency of the MMP-1 2G allele was higher and that of the 1G homozygote was lower in the OSCC cases (p = 0.034). A multivariate logistic regression analysis revealed that subjects who were 45 years old or older had a significantly increased (2.47-fold) risk of OSCC (95%CI 1.47-4.14, p = 0.0006), and those carrying the MMP-1 2G allele had a 2.30-fold risk (95%CI 1.15-4.58, p = 0.018), indicating independent involvement of these factors in OSCC. One of the key discoveries of this research is the apparent reduction of the MMP-1 1G/1G and 1G/2G genotype distributions among the early onset OSCC cases under the ages of 45 years. It should be noted that the tongue was the primary site in 86.2% of these early onset cases. This could suggest the specific carcinogenic mechanisms, i.e. specific carcinogenic stimulations and/or genetic factors in the tongue. CONCLUSION: Since the 2G allele is a majority of the MMP-1 genotype in the general population, it seems to act as a genetic pre-condition in OSCC development. However this report suggests a crucial impact of the MMP-1 2G allele in the early onset OSCC.

Model-based reinforcement learning for partially observable games with sampling-based state estimation.

Games constitute a challenging domain of reinforcement learning (RL) for acquiring strategies because many of them include multiple players and many unobservable variables in a large state space. The difficulty of solving such realistic multiagent problems with partial observability arises mainly from the fact that the computational cost for the estimation and prediction in the whole state space, including unobservable variables, is too heavy. To overcome this intractability and enable an agent to learn in an unknown environment, an effective approximation method is required with explicit learning of the environmental model. We present a model-based RL scheme for large-scale multiagent problems with partial observability and apply it to a card game, hearts. This game is a well-defined example of an imperfect information game and can be approximately formulated as a partially observable Markov decision process (POMDP) for a single learning agent. To reduce the computational cost, we use a sampling technique in which the heavy integration required for the estimation and prediction can be approximated by a plausible number of samples. Computer simulation results show that our method is effective in solving such a difficult, partially observable multiagent problem.

Influence of radial clearance and rotor motion to hemolysis in a journal bearing of a centrifugal blood pump.

Hemolysis due to narrow clearance of noncontact bearings is a critical problem for rotary blood pumps. We developed a centrifugal blood pump with a magnetic and hydrodynamic hybrid bearing, and found that the hemolysis in the narrow clearance depends not only on the clearance size, but also on the rotor stability. In this study, we quantified the relation between the hemolysis, radial clearance (c), and rotor stability through the measurement of the rotor motion and hemolysis. As a result, it was confirmed that the rotor of the current pump is stabilized within the oscillation of 20 microm in blood, and the hemolysis decreases with increase in the c, which is the opposite in the unstable rotor motion with the previous pump. In order to theoretically discuss this hemolysis tendency, we implemented hemolysis estimation in the c according to hydrodynamics and hemodynamics. This estimation can represent the measured hemolysis tendency, and revealed that the flow rate has large influence on the hemolysis in the c.

Measurement of the rotor motion and corresponding hemolysis of a centrifugal blood pump with a magnetic and hydrodynamic hybrid bearing.

This study proposed a centrifugal blood pump with a novel magnetic and hydrodynamic hybrid passive bearing, which consisted of a plain journal bearing for radial stability and a permanent magnetic bearing for axial and tilting stability. We measured the radial motion of the bearing and performed hemolysis tests for the different radial clearance sizes. In the results, it appeared that the radial motion had two modes: the stable center mode, in which the radius of the radial motion rapidly converged to less than 20 microm; and the unstable circle mode, in which the rotor suspension linearly increased with the rotation speed. It also appeared that the pumps with the radial clearance of 80 microm caused more hemolysis than with the smaller clearance sizes in the circle mode. The circle mode was avoidable by the higher rotation or the asymmetric pump structure, but the mechanism of hemolysis in this mode was still unclear.

Risk evaluation of coronary heart disease and cerebrovascular disease by the Japan Atherosclerosis Society Guidelines 2002 using the cohort of the Holicos-PAT study.

Our purpose in this study was to evaluate the new JAS guidelines as a risk assessment tool in Japanese patients with hypercholesterolemia, using the cohort of the Holicos-PAT study. The Holicos-PAT study was designed as a prospective observational study. 2039 patients were followed with or without pravastatin for 5 years. We assessed coronary heart disease (CHD) and cerebrovascular disease (CVD) risks by the patient categories described in the JAS guidelines. In the Holicos-PAT study, the primary endpoints were CHD, and the secondary endpoints were CVD and total mortality. CHD event includes onset and worsening of angina pectoris, performing CABG or PTCA, non-fatal and fatal myocardial infarction, and death from CHD including heart death and sudden death. CVD events are onset or recurrence of cerebral infarction, onset of cerebral hemorrhage, and death from cerebral infarction or hemorrhage. The event rates were calculated by the person-years method, and the differences in event rates between category groups were analyzed by chi-square test. The event rates of CHD in Category A, B1, B2, B3, B4 and C, were 1.1, 4.0, 2.8, 5.7, 18.2 and 38.8 per 1,000 person-years. The rates of CHD events in the higher risk category groups, Category B4 group (p = 0.004 in whole patients) and C group (p < 0.001 in whole patients), were significantly higher than that in the combined category groups A + B1 + B2. The event rates of CVD in Category A, B1, B2, B3, B4 and C, were 2.1, 1.8, 1.8, 0.6, 10.8 and 6.4 per 1,000 person-years. The event rates of CHD in men were significantly higher than those in women, in categories B4 (p < 0.001) and C (p < 0.001). From these results, each category classified by accumulation of risk factors, showed increasing event rates of CHD and CVD. The categories in the JAS guidelines are useful to assess CHD and CVD risk in Japanese patients with hypercholesterolemia. However, the risk evaluation by the JAS guideline categories may underestimate the risk in men and overestimate it in women.

Simultaneous early adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach associated with Helicobacter pylori infection.

The simultaneous association of gastric carcinoma with gastric lymphoma is a rare event. Recent studies have suggested that not only gastric cancer but also primary gastric lymphomas, especially those of mucosa-associated lymphoid tissue (MALT) type, are associated with Helicobacter pylori infection. We report on a 51-year-old woman who was referred to our hospital for the evaluation of abnormal shadows revealed by an upper gastrointestinal radiography series. Endoscopy of the upper gastrointestinal tract revealed early cancer in the middle body of the stomach. Biopsy of the lesion subsequently proved it to be a signet-ring cell carcinoma. Total gastrectomy was performed, under a diagnosis of early gastric carcinoma. The resected specimen revealed two grossly separate lesions. Histological examination confirmed that the gastric body lesion was compatible with early moderately differentiated tubular adenocarcinoma of type 0-IIc, while the lesion of the fundus corresponded to MALT lymphoma. H. pylori was detected, and chronic gastritis was also present in the resected gastric specimen. H. pylori infection may have played a major role in the development of both the MALT lymphoma and the adenocarcinoma of the stomach in this patient.

Identification of potential biomarkers of lymph node metastasis in oral squamous cell carcinoma by cDNA microarray analysis.

We surveyed the expression of 557 cancer-related genes in 15 cases of well-differentiated OSCC by cDNA microarray analysis. To identify potential biomarkers for lymph node metastasis, all microarray data were compared by the Mann-Whitney test and the significance analysis of microarrays between OSCCs with and those without lymph node metastasis. The tissues of OSCCs with lymph node metastasis exhibited increased expression levels of MMP-1, MMP-3, uPA, integrin-alpha3, paxillin, tenascin C and IL-6 transcripts. All of these genes were included in common clusters on the Cluster/TreeView analysis, implying that functional gene groups of proteolytic enzymes and integrin-related molecules are involved in cervical lymph node metastasis. The results of RTQ-PCR for differentially expressed genes were in accord with those of cDNA microarray analyses, suggesting that the data obtained by microarray gene expression analyses were valid. Consistent with cooperative expression patterns, immunohistochemical analyses demonstrated that products of MMP-1, MMP-3 and uPA were colocalized to components of the neoplastic stroma, particularly mononuclear inflammatory cells with well-developed eosinophilic cytoplasm. Our results suggest that expression levels of molecules involved in tissue remodeling and cell-ECM adhesion, especially MMP-1 and integrin-alpha3, can provide an accurate biomarker system for predicting the risk of cervical lymph node metastasis in OSCC.