The poly(A) polymerase beta gene may not be associated with azoospermia caused by Sertoli-cell-only syndrome in Japanese patients by comparing patients and normal controls.

Approximately 15% of couples are infertile, with half of these cases being due to a male factor. Testis-specific cytoplasmic poly(A) polymerase beta (PAPOLB) is known to be critical for spermatogenesis. In mice, the loss of function of the Papolb gene results in the arrest of spermiogenesis and in male infertility. To analyse the role of the PAPOLB gene in human male infertility, this study investigated the relevance of this gene to human Sertoli-cell-only syndrome (SCOS) with azoospermia. Mutation analysis of the PAPOLB coding region was performed on 139 Japanese patients by PCR and direct sequence analysis. No critical mutations directly causing SCOS were detected, but three single-nucleotide polymorphisms (SNPs; SNP1 (c1101C > T), SNP2 (c1347T > C) and SNP3 (c1903C > A)) were found in the coding region. However, there were no significant associations in the allelic and genotypic distributions of these three SNPs between the SCOS and control groups (p>.05). This study suggests a lack of association of PAPOLB with azoospermia due to SCOS in humans.

Time trends in suicide rates by domestic gas or car exhaust gas inhalation in Japan, 1968-1994.

AIMS: A reduction in the carbon monoxide content of domestic gas and car exhaust gas has been associated with a decrease in gassing suicides in many western countries. In Japan, a reduction in the carbon monoxide content of domestic gas supply began in the early 1970s, and carbon monoxide emissions standards of new passenger cars were significantly strengthened in 1978. However, little is known about the impact of detoxification of these gases on gassing-related suicides in Japan. Therefore, we examined the changing patterns of suicide due to domestic gas or car exhaust gas inhalation by gender and age in Japan between 1968 and 1994. METHODS: Suicide mortality data were obtained from the Vital Statistics of Japan. In this study, age was divided into four groups: 15-24, 25-44, 45-64 and 65+ years. Method of suicide was divided into three groups: domestic gas, car exhaust gas and non-gases. We calculated method-specific age-standardised suicide rates by gender within each of the four age groups. We applied joinpoint regression to the data and quantified the observed changes. RESULTS: Suicide rates by domestic gas, regardless of gender and age, increased from 1968 to the mid-1970s and then decreased sharply. The proportion of all suicides accounted for by domestic gas was comparatively high in the mid-1970s among females aged 15-24 and 25-44 years, while for other gender-age-groups the proportion of domestic gas suicides remained small, even at the peak. For females aged 15-44 years, the decrease in domestic gas suicides appeared to cause a substantial decrease in overall suicides in this gender/age group. Car exhaust gas was a more common method for males, particularly those aged 25-64 years. Car exhaust gas suicide rates for males aged 25-64 years peaked in the mid-1980s, followed by a sharp decrease. CONCLUSIONS: A reduction in the carbon monoxide content of the domestic gas, which began in the early 1970s in Japan, was associated with a decrease in domestic gas suicides for both genders of all ages. Concerning females aged 15-44 years, a decrease in domestic gas suicides caused a substantial decrease in overall suicides in this gender/age group since the proportion of domestic gas suicides among all suicides combined was comparatively large. However, it remains uncertain whether the introduction of catalytic converters in the 1970s in Japan resulted in a reduction of suicides from car exhaust gas inhalation.

Time trends in method-specific suicide rates in Japan, 1990-2011.

BACKGROUND: Little is known about whether particular suicide methods have contributed differently to the recent unfavourable suicide mortality trends in Japan. Analysing such trends may shed light on the effect of potentially preventable factors, such as the impact of restricting access to certain popular suicide methods, on overall rates. Therefore, we assessed recent trends in method-specific suicide by gender and age in Japan. METHOD: Suicide mortality and population data between 1990 and 2011 were obtained from the Vital Statistics of Japan and used to calculate method-specific mortality rates. Suicide methods were divided into seven groups: overdose, gases, hanging, drowning, cutting, jumping and other means. Age was divided into four groups: 15-24, 25-44, 45-64 and 65+ years. We applied joinpoint regression to the data and quantified the observed changes. RESULTS: The results of the joinpoint regression analyses showed a sharp increase in overall suicide rates for males and females of all ages until the late 1990s. Suicide from hanging and jumping, in particular, contributed to this increase. After 2000, an increasing trend in overall suicide rates in both males and females aged 15-24 and 25-44 years was observed, with overdose, gases and hanging contributing to this increasing trend. CONCLUSIONS: Our findings revealed that different suicide methods varied in their contribution to the recent overall suicide transition in Japan. Regarding factors associated with the recent increase in suicides by overdose, gases, hanging and jumping, further research is needed in order to promote and implement effective means restriction strategies.

Superlinear and sublinear urban scaling in geographical networks modeling cities.

Using a geographical scale-free network to describe relations between people in a city, we explain both superlinear and sublinear allometric scaling of urban indicators that quantify activities or performances of the city. The urban indicator Y(N) of a city with the population size N is analytically calculated by summing up all individual activities produced by person-to-person relationships. Our results show that the urban indicator scales superlinearly with the population, namely, Y(N)∝N(ß) with ß>1, if Y(N) represents a creative productivity and the indicator scales sublinearly (ß<1) if Y(N) is related to the degree of infrastructure development. These results coincide with allometric scaling observed in real-world urban indicators. We also show how the scaling exponent ß depends on the strength of the geographical constraint in the network formation.

Phosphorus flame retardants in indoor dust and their relation to asthma and allergies of inhabitants.

Organophosphate esters are used as additives in flame retardants and plasticizers, and they are ubiquitous in the indoor environment. Phosphorus flame retardants (PFRs) are present in residential dust, but few epidemiological studies have assessed their impact on human health. We measured the levels of 11 PFRs in indoor floor dust and multi-surface dust in 182 single-family dwellings in Japan. We evaluated their correlations with asthma and allergies of the inhabitants. Tris(2-butoxyethyl) phosphate was detected in all samples (median value: 580 µg/g in floor dust, 111 µg/g in multi-surface dust). Tris(2-chloro-iso-propyl) phosphate (TCIPP) was detected at 8.69 µg/g in floor dust and 25.8 µg/g in multi-surface dust. After adjustment for potential confounders, significant associations were found between the prevalence of atopic dermatitis and the presence of TCIPP and tris(1,3-dichloro-2-propyl) phosphate in floor dust [per log10 -unit, odds ratio (OR): 2.43 and 1.84, respectively]. Tributyl phosphate was significantly associated with the prevalence of asthma (OR: 2.85 in floor dust, 5.34 in multi-surface dust) and allergic rhinitis (OR: 2.55 in multi-surface dust). PFR levels in Japan were high compared with values reported previously for Europe, Asia-Pacific, and the USA. Higher levels of PFRs in house dust were related to the inhabitants' health status.

Single-nucleotide polymorphisms in the LRWD1 gene may be a genetic risk factor for Japanese patients with Sertoli cell-only syndrome.

Genetic mechanisms have been implicated as a cause of some cases of male infertility. Recently, ten novel genes involved in human spermatogenesis, including human LRWD1, have been identified by expression microarray analysis of human testictissue. The human LRWD1 protein mediates the origin recognition complex in chromatin, which is critical for the initiation of pre-replication complex assembly in G1 and chromatin organization in post-G1 cells. The Lrwd1 gene expression is specific to the testis in mice. Therefore, we hypothesized that mutation or polymorphisms of LRWD1 participate in male infertility, especially azoospermia. To investigate whether LRWD1 gene defects are associated with azoospermia caused by SCOS and meiotic arrest (MA), mutational analysis was performed in 100 and 30 Japanese patients by direct sequencing of the coding regions, respectively. Statistical analysis was performed for patients with SCOS and MA and in 100 healthy control men. No mutations were found in LRWD1; however, three coding single-nucleotide polymorphisms (SNP1-SNP3) could be detected in the patients. The genotype and allele frequencies in SNP1 and SNP2 were notably higher in the SCOS group than in the control group (P < 0.05). These results suggest the critical role of LRWD1 in human spermatogenesis.

Relationship between cytokine single nucleotide polymorphisms and sarcoidosis among Japanese subjects.

Several susceptibility genes for sarcoidosis have been identified, but their relationship to the clinical state and prognosis remains to be elucidated. The aim of this study was to elucidate the relationship between sarcoidosis and five single nucleotide polymorphisms (SNPs) of three cytokines expected to play an important role in the inflammatory response. A case-control study was performed with 208 unrelated patients who met the diagnostic criteria for sarcoidosis used in Japan since 2006, and 328 control subjects. Five SNPs were analyzed: interleukin (IL)-10-819T/C (rs1800871), IL-10-592A/C(rs1800872), IL-6-634C/G (rs1800796), tumor necrosis factor-alpha (TNF-alpha)-857C/T (rs1799724), and TNF-alpha -1031T/C (rs1799964). No significant differences in SNPs were observed between the total sarcoidosis and control groups. However, the prevalence of rs1800871 and rs1800872 polymorphisms differed significantly in the sarcoidosis with eye involvement group compared with the control group [rs1800871 TT (vs. TC + CC): OR = 1.67, P = 0.034; rs1800872 AA (vs. AC + CC): OR = 1.66, P = 0.036]. Analyzing the cardiac involvement group, the prevalence of the rs1799724 polymorphism was significantly different from that of the control group [rs1799724 TT (vs. CC + CT): OR = 6.01. P = 0.006]. We concluded that the rs1799724 C/T polymorphism may affect susceptibility to cardiac sarcoidosis, while the rs1800871 T/C and rs1800872A/C polymorphisms may affect susceptibility to sarcoidosis with eye involvement.

Updated overall survival results from a randomized phase III trial comparing gefitinib with carboplatin-paclitaxel for chemo-naïve non-small cell lung cancer with sensitive EGFR gene mutations (NEJ002).

BACKGROUND: NEJ002 study, comparing gefitinib with carboplatin (CBDCA) and paclitaxel (PTX; Taxol) as the first-line treatment for advanced non-small cell lung cancer (NSCLC) harboring an epidermal growth factor receptor (EGFR) mutation, previously reported superiority of gefitinib over CBDCA/PTX on progression-free survival (PFS). Subsequent analysis was carried out mainly regarding overall survival (OS). MATERIALS AND METHODS: For all 228 patients in NEJ002, survival data were updated in December, 2010. Detailed information regarding subsequent chemotherapy after the protocol treatment was also assessed retrospectively and the impact of some key drugs on OS was evaluated. RESULTS: The median survival time (MST) was 27.7 months for the gefitinib group, and was 26.6 months for the CBDCA/PTX group (HR, 0.887; P=0.483). The OS of patients who received platinum throughout their treatment (n=186) was not statistically different from that of patients who never received platinum (n=40). The MST of patients treated with gefitinib, platinum, and pemetrexed (PEM) or docetaxel (DOC, Taxotere; n=76) was around 3 years. CONCLUSIONS: No significant difference in OS was observed between gefitinib and CBDCA/PTX in the NEJ002 study, probably due to a high crossover use of gefitinib in the CBDCA/PTX group. Considering the many benefits and the risk of missing an opportunity to use the most effective agent for EGFR-mutated NSCLC, the first-line gefitinib is strongly recommended.

Coexistence of fibrotic and chondrogenic process in the capsule of idiopathic frozen shoulders.

OBJECTIVE: To analyze changes in the capsule from idiopathic frozen shoulders and clarify their etiology. MATERIALS AND METHODS: Samples (the rotator interval capsule, middle glenohumeral ligament (MGHL), and inferior glenohumeral ligament (IGHL)) were collected from 12 idiopathic frozen shoulders with severe stiffness and 18 shoulders with rotator cuff tears as a control. The number of cells was counted and the tissue elasticity of the samples was calculated by scanning acoustic microscopy (SAM). The amount of glycosaminoglycan content was assessed by alcian blue staining. Gene and protein expressions related to fibrosis, inflammation, and chondrogenesis were analyzed by quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC). Furthermore, the total genes of the two groups were compared by DNA microarray analysis. RESULTS: The number of cells was significantly higher and the capsular tissue was significantly stiffer in idiopathic frozen shoulders compared with shoulders with rotator cuff tears. Staining intensity of alcian blue was significantly stronger in idiopathic frozen shoulders. Gene expressions related to fibrosis, inflammation, and chondrogenesis were significantly higher in idiopathic frozen shoulders compared with shoulders with rotator cuff tears assessed by both qPCR and DNA microarray analysis. CONCLUSION: In addition to fibrosis and inflammation, which used to be considered the main pathology of frozen shoulders, chondrogenesis is likely to have a critical role in pathogenesis of idiopathic frozen shoulders.

Relationships between mite allergen levels, mold concentrations, and sick building syndrome symptoms in newly built dwellings in Japan.

UNLABELLED: This study investigated the possible relationships between exposures to mite allergen and airborne fungi with sick building syndrome (SBS) symptoms for residents living in newly built dwellings. We randomly sampled 5709 newly built dwellings in six prefectures from northern to southern Japan. A total of 1479 residents in 425 households participated in the study by completing questionnaire surveys and agreeing to environmental monitoring for mite allergen (Der 1), airborne fungi, aldehydes, and volatile organic compounds. Stepwise logistic regression analyses adjusted for confounders were used to obtain odds ratios (OR) of mite allergen and fungi for SBS symptoms. Der 1 had a significantly high OR for nose symptoms. Rhodotorula had a significantly high OR for any symptoms, and Aspergillus had significantly high OR for eye symptoms. However, the total colony-forming units had a significantly low OR for throat and respiratory symptoms. Eurotium had a significantly low OR for skin symptoms. In conclusion, dust-mite allergen levels and indoor airborne Rhodotorula and Aspergillus concentrations may result in SBS symptoms in newly built dwellings. PRACTICAL IMPLICATIONS: Various factors can cause sick building syndrome symptoms. This study focused on biologic factors such as dust-mite allergen and airborne fungi in newly built dwellings in Japan. Dust-mite allergen levels were significantly associated with higher rates of nose symptoms, airborne Rhodotorula concentrations were significantly associated with higher rates of any symptoms, and Aspergillus concentrations were significantly associated with higher rates of eye symptoms. Measures should be taken to reduce mite allergen levels and fungal concentrations in these dwellings.

Randomized phase II trial of weekly paclitaxel combined with carboplatin versus standard paclitaxel combined with carboplatin for elderly patients with advanced non-small-cell lung cancer.

BACKGROUND: The optimal platinum doublet regimen in elderly patients with non-small-cell lung cancer (NSCLC) is still uncertain. We conducted a randomized phase II study to compare the efficacy and safety of weekly paclitaxel combined with carboplatin with those of the standard schedule. PATIENTS AND METHODS: Elderly patients (age > or =70 years) with advanced NSCLC were randomly assigned to either the weekly arm {70 mg/m(2) paclitaxel on days 1, 8, and 15 and carboplatin [area under the curve (AUC) = 6] on day 1} or the standard arm [200 mg/m(2) paclitaxel and carboplatin (AUC = 6) on day 1]. The primary end point was the overall response rate (ORR). RESULTS: Eighty-two patients were enrolled. The ORR and median progression-free survival were 55% and 6.0 months for the weekly arm and 53% and 5.6 months for the standard arm. Grade 3/4 neutropenia and peripheral neuropathy were observed in 41% and 0% of the patients in the weekly arm and in 88% and 25% in the standard arm, respectively. CONCLUSIONS: This is the first randomized study that compares the platinum doublet designed specifically for the elderly. Regarding the safety, the weekly regimen was less toxic than the standard regimen and seems to be preferable for elderly patients with advanced NSCLC.

Association between indoor exposure to semi-volatile organic compounds and building-related symptoms among the occupants of residential dwellings.

UNLABELLED: The aim of this study was to evaluate the levels of semi-volatile compounds (SVOCs) in residential detached houses in Sapporo, Japan, and whether exposure to these SVOCs was associated with the development of building-related symptoms named 'sick house syndrome' (SHS). The definition of SHS is fundamentally the same as that of the sick building syndrome (SBS). The presence of symptoms of SHS was evaluated using a validated self-administered questionnaire. Surveys and samplings of air and house dust in 41 dwellings were performed from October 2006 to January 2007, and 134 occupants responded to questionnaires. Samples were analyzed to quantify the concentrations of eight plasticizers, eleven phosphate triester flame retardants, two alkyl phenols used as anti-oxidants, and one organochlorine synergist called s-421, by gas chromatography-mass spectrometry and gas chromatography-flame photometry. The compounds frequently detected were di-n-butylphthalate, di(2-ethylhexyl)phthalate (DEHP), and dibutylhydroxytoluene in air, and DEHP and tris(2-butoxyethyl)phosphate (TBEP) in dust. Tributylphosphate was strongly and directly associated with mucosal symptoms of SHS; s-421 was also directly associated with mucosal symptoms of SHS. On the contrary, some chemicals such as diethylphthalate and TBEP were inversely associated with SHS. In future studies, we plan to assess these associations in a larger population. PRACTICAL IMPLICATIONS: This study suggests that it may be possible to reduce building-related symptoms by altering exposure to certain SVOCs, such as tributylphosphate commonly found in ceiling and wall coverings and s-421 used as a synergist for pyrethroids. The association between SHS and s-421 suggested that use of pyrethroid insecticides could elicit symptoms of SHS. However, further studies are necessary to test the associations observed in the present study and to examine whether the SVOCs associated with symptoms are causative agents or simply surrogates for some other factor that is causing the symptoms.

Assessment of synchronization measures for effective ventricular support by using the shape memory alloy fibred artificial myocardium in goats.

Thromboembolic and haemorrhagic complications are the primary causes of mortality and morbidity in patients with artificial hearts, which are known to be induced by the interactions between blood flow and artificial material surfaces. The authors have been developing a new mechanical artificial myocardial assist device by using a sophisticated shape memory alloy fibre in order to achieve the mechanical cardiac support from outside of the heart without a direct blood contacting surface. The original material employed as the actuator of artificial myocardial assist devices was 100um fibred-shaped, which was composed of covalent and metallic bonding structure and designed to generate 4-7 % shortening by Joule heating induced by the electric current input. In this study, we focused on the synchronization of the actuator with native cardiac function, and the phase delay parameter was examined in animal experiments using Saanen goats. Total weight of the device including the actuator was around 150g, and the electric power was supplied transcutaneously. The device could be successfully installed into thoracic cavity, which was able to be girdling the left ventricle. The contraction of the device could be controlled by the originally designed microcomputer. The mechanical contraction signal input had been transmitted with the phase delay of 50-200 msec after the R-wave of ECG, and hemodynamic changes were investigated. Cardiac output and systolic left ventricular pressure were elevated with 20% delay of cardiac cycle by 27% and 7%, respectively, although there was smaller difference under the condition of the delay of over 30%. Therefore, it was suggested that the synchronization measures should be examined in order to achieve sophisticated ventricular passive/active support on physiological demand.

Regional differences in residential environments and the association of dwellings and residential factors with the sick house syndrome: a nationwide cross-sectional questionnaire study in Japan.

UNLABELLED: This study was conducted to clarify regional differences in residential factors and the association of those factors with dwellings having sick house syndrome (SHS) problems. The survey was conducted in six areas of northern and southern Japan. In terms of regional differences, dampness was not as severe in the dwellings in Sapporo as compared with that in areas in the south. SHS was defined using five categories of nasal, throat and respiratory, skin and general symptoms, which appeared frequently or not frequently and improved upon leaving the home. The dampness index was estimated by the sum of the presence of several indicators: condensation on the window panes and/or wall, visible mold growth, moldy odor, slow-drying wet towels in the bathroom, and water leakage. The dwellings where inhabitants showed any symptoms of SHS comprised 3.7% of all surveyed dwellings. We found significant associations between SHS and dampness index, odors, and stuffiness of the air. For dampness, the adjusted odds ratio (OR) increased with increased dampness index, adjusting for the age of the house, pets indoors, stuffiness of the air, and odors. These results showed an increased risk when several dampness indicators appeared simultaneously. PRACTICAL IMPLICATIONS: To evaluate the associations of residential environments and Sick House Syndrome (SHS), this cross-sectional questionnaire study was conducted on 2297 dwellings in six areas in Japan from 2003 to 2004. The dwellings where inhabitants showed any of nasal, throat and respiratory, skin and general symptoms comprised 3.7% of all surveyed dwellings, and an increased risk for SHS was found when several dampness indicators, 'condensation', 'visible mold growth', 'moldy odor', 'slow drying wet towels in the bathroom' and 'water leakage', appeared simultaneously.

Proinflammatory cytokine polymorphisms and the risk of preterm birth and low birthweight in a Japanese population.

Pregnancy and parturition involve a complex and poorly understood molecular and biological interplay between mother and fetus. Inflammatory cytokines have been reported to be associated with fetal growth and parturition. The aim of this study was to examine whether common proinflammatory cytokine polymorphisms are associated with preterm birth (PTB), low birthweight or intrauterine growth restriction in a Japanese population. We assessed a consecutive series of 414 women who had singleton deliveries in Sapporo, Japan between 2001 and 2005. Genotyping of IL1A -889C/T, +4845G/T (A114S), IL1B -511C/T, -31C/T, IL2 -384T/G and IL6 -634C/G polymorphisms was determined by an allelic discrimination assay. The risk of PTB significantly increased in women carrying the IL1A -889T allele (CC genotype [reference]; CT genotype, odds ratios (OR): 2.5; 95% confidence intervals (95% CI): 1.4-4.8; CT+TT genotypes [dominant genotype model], OR: 2.5, 95% CI: 1.3-4.6). Similarly, the risk of PTB significantly increased in women carrying the IL1A +4845T allele (GG genotype [reference]; GT genotype, OR: 2.4, 95% CI: 1.3-4.4; GT+TT genotypes [dominant genotype model], OR: 2.3, 95% CI: 1.2-4.2). The frequency of the IL1A TT haplotype in mothers with PTB was significantly higher than in mothers who had a term birth (P < 0.001), whereas the frequency of the IL1A CG haplotype in mothers who had a PTB was significantly lower (P < 0.001). Our findings suggest that the polymorphisms and haplotypes in the IL1A gene are associated with PTB in Japanese women.

Sensorless control for a sophisticated artificial myocardial contraction by using shape memory alloy fibre.

The authors have been developing an artificial myocardium, which is capable of supporting natural contractile function from the outside of the ventricle. The system was originally designed by using sophisticated covalent shape memory alloy fibres, and the surface did not implicate blood compatibility. The purpose of our study on the development of artificial myocardium was to achieve the assistance of myocardial functional reproduction by the integrative small mechanical elements without sensors, so that the effective circulatory support could be accomplished. In this study, the authors fabricated the prototype artificial myocardial assist unit composed of the sophisticated shape memory alloy fibre (Biometal), the diameter of which was 100 microns, and examined the mechanical response by using pulse width modulation (PWM) control method in each unit. Prior to the evaluation of dynamic characteristics, the relationship between strain and electric resistance and also the initial response of each unit were obtained. The component for the PWM control was designed in order to regulate the myocardial contractile function, which consisted of an originally-designed RISC microcomputer with the input of displacement, and its output signal was controlled by pulse wave modulation method. As a result, the optimal PWM parameters were confirmed and the fibrous displacement was successfully regulated under the different heat transfer conditions simulating internal body temperature as well as bias tensile loading. Then it was indicated that this control theory might be applied for more sophisticated ventricular passive or active restraint by the artificial myocardium on physiological demand.

Fractal dimension of 40 MHz intravascular ultrasound radio frequency signals.

OBJECTIVE: Fully automatic tissue characterization in intravascular ultrasound systems is still a challenge for the researchers. The present work aims to evaluate the feasibility of using the Higuchi fractal dimension of intravascular ultrasound radio frequency signals as a feature for tissue characterization. METHODS: Fractal dimension images are generated based on the radio frequency signals obtained using mechanically rotating 40 MHz intravascular ultrasound catheter (Atlantis SR Plus, Boston Scientific, USA) and compared with the corresponding correlation images. CONCLUSION: An inverse relation between the fractal dimension images and the correlation images was revealed indicating that the hard or slow moving tissues in the correlation image usually have low fractal dimension and vice-versa. Thus, the present study suggests that fractal dimension images may be used as a feature for intravascular ultrasound tissue characterization and present better resolution then the correlation images.

Detection and quantification of calcifications in intravascular ultrasound images by automatic thresholding.

An innovative application of automatic thresholding is used for the detection of calcification regions in intravascular ultrasound images. A priori knowledge of the acoustic shadow that usually accompanies calcification regions is used to discriminate these from other bright regions in the image. A method for the calculation of the angle of calcification has also been developed. The proposed algorithms are applied to in-vivo images obtained from left anterior descending coronary arteries during percutaneous transluminal coronary angioplasty (n = 14). The resulting specificity is 72% and the sensitivity 84%. The receiver operating characteristic curve, the area under the curve being equal to 0.91, is plotted to evaluate the algorithm performance.

Morphological approach for the functional improvement of an artificial myocardial assist device using shape memory alloy fibres.

The authors have been developing a mechano-electric artificial myocardial assist system (artificial myocardium) which is capable of supporting natural contractile functions from the outside of the ventricle without blood contacting surface. In this study, a nano-tech covalent type shape memory alloy fibre (Biometal, Toki Corp, Japan) was employed and the parallel-link structured myocardial assist device was developed. And basic characteristics of the system were examined in a mechanical circulatory system as well as in animal experiments using goats. The contractile functions were evaluated with the mock circulatory system that simulated systemic circulation with a silicone left ventricular model and an aortic afterload. Hemodynamic performance was also examined in goats. Prior to the measurement, the artificial myocardial assist device was installed into the goat's thoracic cavity and attached onto the ventricular wall. As a result, the system could be installed successfully without severe complications related to the heating, and the aortic flow rate was increased by 15% and the systolic left ventricular pressure was elevated by 7% under the cardiac output condition of 3L/min in a goat. And those values were elevated by the improvement of the design which was capable of the natural morphological myocardial tissue streamlines. Therefore it was indicated that the effective assistance might be achieved by the contraction by the newly-designed artificial myocardial assist system using Biometal. Moreover it was suggested that the assistance gain might be obtained by the optimised configuration design along with the natural anatomical myocardial stream line.

Targeted delivery of NK4 to multiple lung tumors by bone marrow-derived mesenchymal stem cells.

Most advanced solid tumors metastasize to different organs. However, no gene therapy effective for multiple tumors has yet been developed. Since a unique characteristic of bone marrow-derived mesenchymal stem cells (MSCs) is that they migrate to tumor tissues, we wanted to determine whether MSCs could serve as a vehicle of gene therapy for targeting multiple tumors. First, we confirmed that mouse MSCs preferentially migrate to multiple tumors of the lung in the Colon-26 (C-26) lung metastasis model. Next, MSCs were efficiently transduced with NK4, an antagonist of hepatocyte growth factor (HGF), by an adenoviral vector with an RGD motif. MSCs expressing NK4 (NK4-MSCs) strongly inhibited development of lung metastases in the C-26 lung metastasis model after systemic administration via a tail vein. Treatment with NK4-MSCs significantly prolonged survival of the C-26-tumor-bearing mice by inhibiting tumor-associated angiogenesis and lymphangiogenesis and inducing apoptosis of the tumor cells. MSC-based gene therapy did not induce the severe adverse effects induced by conventional adenoviral vectors. These results indicate that MSCs can serve as a vehicle of gene therapy for targeting multiple lung metastatic tumors.