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Aim Sarcopenia is a harmful condition in patients with chronic liver disease. However, the evaluation of body muscle mass requires expensive instrumentation. The sarcopenia index (SI): (creatinine / cystatin C × 100) has been reported to correlate with muscle volume. A calculated body muscle mass (CBMM) using creatinine, cystatin C, and bodyweight also correlates with muscle mass. We evaluated the applicability of using SIs and CBMMs as screening methods for sarcopenia. Methods Patients (n = 303) with liver damage were evaluated for creatinine, cystatin C, and grip strength (GS). All patients were evaluated using cross-sectional computed tomography images of the third lumbar vertebrae to determine their skeletal muscle (SM) mass. CBMMs and SIs were compared with SMs, GSs, and sarcopenia. Results Correlation coefficients (R) between SMI (SM / height2 [m2 ]) and CBMM, and between GS and CBMM were 0.643 and 0.723, respectively. Factors contributing to low GSs; low SM indices; and sarcopenia were age and SM; sex, age, GS, SI, and CBMM indices; and sex, bodyweight, and CBMM, respectively, in the multivariate logistic analyses. Receiver operating characteristic curve analysis between sarcopenia and CBMM showed an area under the receiver operating characteristic curve of 0.78504 in women and 0.86067 in men. Cut-off CBMM values for sarcopenia were 27.903 (sensitivity 0.73958) in women and 39.731 (sensitivity 0.7941) in men. Conclusions CBMMs and SIs are simple and minimally invasive screening methods in which low levels are indicative of sarcopenia in patients with liver disease.

Tuberous sclerosis complex (TSC) is a genetic disorder involving a variety of physical manifestations, and is associated with epilepsy and multiple serious neuropsychiatric symptoms. These symptoms are collectively known as TSC-associated neuropsychiatric disorders (TAND), which is a severe burden for patients and their families. Overactivation of the mechanistic target of rapamycin complex 1 (mTORC1) by mutations in TSC1 or TSC2 is thought to cause TSC, and mTORC1 inhibitors such as sirolimus and everolimus are reported to be effective against various tumor types of TSC. However, there are various reports on the effect of mTORC1 inhibitor therapy on TAND in patients with TSC, which may or may not be effective. In our previous investigations, we generated TSC2 conditional knockout mice (Mitf-Cre, Tsc2 KO; Tsc2 cKO). These mice developed spontaneous epileptic activity. In the current study, we further analyzed the detailed behaviors of Tsc2 cKO mice and confirmed that they exhibited phenotypes of TAND as well as epileptic seizures, indicating that Tsc2 cKO mice are a useful model for TAND. Furthermore, the olfactory bulb and piriform cortex caused epilepsy and TAND in Tsc2 cKO mice, and neurodegeneration was observed. Immunohistology and immunophenotypic analysis of cells, and quantitative RT-PCR suggested that changes in microglial polarity were involved in the onset of TSC epilepsy and neuropsychiatric symptoms. Although the effect of mTORC1 inhibitors on TAND has not been established, the results of this study might help elucidate the mechanism of TAND pathogenesis and suggest that sirolimus may be a valuable therapeutic tool for TAND.

In order to establish a minimally invasive and safe liver regenerative technology, a technique for fabricating liver tissue possessing a vascular network was developed by subcutaneously transplanting a cell sheet composed of primary human hepatocytes and normal fibroblasts. However, differences in fibroblast characteristics owing to donor age may threaten the stability of liver tissue regenerated via this technology. Herein we describe the influence of fibroblasts from multiple donors on the fabrication of engineered human hepatocyte tissues in vitro and in vivo. Primary human hepatocytes were cultured with seven strains of fibroblasts derived from the skins of donors of various ages, ranging from a fetus (12 weeks) to the elderly (69 years). Engineered hepatocyte sheets were successfully harvested for all strains. At 2 weeks after the subcutaneous transplantation of the hepatocyte sheets into mice, the highest human albumin (hALB) serum concentration was noted in the mouse containing fibroblasts from a 12 year old (TIG-118). Since the platelet-derived growth factor subunit B (PDGFB) gene expression of TIG-118 cells was significantly higher than that in the other cells, PDGFB may be considered to play an important role in the initial subcutaneous engraftment of primary human hepatocytes. Even though hALB concentration exhibited a parabolic tendency with age, there was no statistically significant difference noted within 6–8 weeks after transplantation. The present study demonstrates that this technology can produce consistent and stable hepatocyte sheets that exhibit long-term survival and liver-specific functionality in vivo regardless of the fibroblast donor age.

Objectives The purpose of this study was to identify elements that cancer peer supporters working in Japanese hospitals consider to be important in helping them perform their role.Methods A qualitative inductive research was conducted. Introductions to potential participants were obtained from a patient association that agreed to help with the study. Interviews were conducted from July through October 2014, using an interview guide, with cancer peer supporters who consented to participate in the study. Elements they perceived as important to the performance of their role were inductively identified from interview transcripts. The analysis consisted of coding phrases in the text and organizing the codes generated into categories and subcategories.Results The study participants consisted of 10 cancer peer supporters (2 men, 8 women), in the age range of 40 to 70 years, who provided private counseling and worked in cancer support groups in hospitals. The analysis generated 129 codes, 11 subcategories, and 5 categories. These 5 categories were: [1.Help service users determine their own paths by listening to and accepting what they say with a non-judgmental attitude]; [2.Offer a perspective distinct from that of the medical staff]; [3.Think of ways to achieve a good balance between one's personal life and cancer peer support work while maintaining a stable state of mind]; [4.Ensure that one maintains the necessary knowledge and skills, and continually improve oneself]; and [5.Build relationships of trust with medical staff and the hospital].Conclusion Category [1] and category [2] were behaviors regarded as important when interacting with users. They were "matters regarded as important during the practice of cancer peer support working for users," and comprised the core of matters that were regarded as important. Next, as for matters regarded as important in relation to the supporters themselves, the categories were [3] and [4]. These were "matters regarded as important for continuity and qualitative improvement of cancer peer support working." Areas that call for improvement in relation to this are preparation of support systems and learning environments. Another matter regarded as important was category [5]. This was a "matter regarded as important to smoothen and facilitate cancer peer support working." Placing importance on relationships of trust with medical staff and hospitals could be considered a distinctive characteristic of cancer peer supporters working at hospitals.

Subcutaneous transplantation of engineered hepatocyte/fibroblast sheets (EHFSs) is a low invasive and safe approach to construct vascularized subcutaneous human liver tissue (VSLT). However, the liver-specific structures and functionalities in the development process of VSLTs in mice remain poorly understood. Here, we describe time-dependent characteristics of the formation of the vascular network, cell-cell adhesions, liver transporters, liver-specific protein synthesis, and metabolizing activities. The EHFSs formed multilayered thick tissues by rapid neovascularization, which allows overcoming extremely difficult problems, such as the lack of oxygen supply on the formation of three-dimensional primary hepatocyte tissue under the skin. The blood vessels consisted of mouse-origin endothelial cells (ECs) (mVEGFR2) from the subcutaneous space at 1-7 days, and the following formation of the vascular network was performed by human-origin ECs (hVEGFR2). Many varieties of liver-specific gene expressions increased with the construction of the VSLTs: cell-cell adhesion molecules (CDH1, CLDN3, and CX32), transporters at basal (OATP1A1, OCT1, and NTCP) and apical membranes (MRP2, MDR1, and BSEP), blood coagulation factors (F8 and F9), urea synthesis (CPS1, OTC, and ARG1), and metabolism enzymes (CYP7A1, CYP1A2, CYP2B6, CYP3A4, and UGT1A1). Subacute hepatic failure model mice with VSLT were alive at least 7 weeks after liver damage. Thus, the ectopic liver organ offers the potential for a low invasive and safe treatment for liver diseases.

Indoxyl sulfate (IS), a protein-bound uremic toxin, induces renal disorders and atrial fibrillation (AF). It is well known that renal dysfunction is a risk factor for AF and radiofrequency catheter ablation (RFCA) improves the renal function. However, the improvement in the renal function after RFCA in patients with early stage chronic kidney disease (CKD) and the serial changes in the IS level have not been fully elucidated. This study aimed to investigate whether IS affects the improvement in the renal function. A total of 91 consecutive patients with mild kidney dysfunction (CKD stage I-II) who underwent RFCA and maintained sinus rhythm were prospectively enrolled. The plasma IS level and estimated glomerular filtration rate (eGFR) were determined before, 3 months, and 1 year after RFCA. The patients were divided according to the IS quartiles (Q1-4;0.4, 0.4-0.7, 0.7-1.2, and1.2 μg/ml). There was no significant difference in the eGFR among the IS quartiles. A significantly higher eGFR improvement rate was obtained for IS-Q4 than the other quartiles (p = 0.039). The IS-Q4 IS level significantly decreased at 1 year after RFCA (1.8 ± 0.8 to 1.2 ± 0.7 μg/ml, p 0.01). The multivariable logistic model revealed that a high-IS level (IS-Q4) was an independent predictor of an eGFR improvement (OR 3.33; 95% CI 1.16-9.59; p = 0.026). A high-IS level reduction after RFCA improved the renal function in AF patients with mild kidney dysfunction.

Serum creatinine (Cr)-based glomerular filtration rate (CrGFR) is overestimated in liver disease. The present study evaluated whether the difference in CrGFR and cystatin C (CysC) GFR (dGFR) is significant in liver disease. The Cr-to-CysC ratio and sarcopenia index (SI) have been reported to correlate with muscle volume. An estimated total body muscle mass with Cr, CysC and calculated body muscle mass (CBMM) has also been reported to correlate with muscle mass. The applicability of dGFR, SI and CBMM for liver disease were evaluated. A total of 313 patients with liver damage were evaluated for Child-Pugh score, albumin-bilirubin (ALBI) score, model for end-stage liver disease, fibrosis-4, Cr, CysC, Cr-based estimated GFR (CreGFR), CysCGFR and grip strength. Of the 313 patients, 199 were evaluated using cross-sectional computed tomography (CT) of the third lumbar vertebra to determine the skeletal muscle (SM) mass. dGFR, CBMM and SI were compared to liver damage, muscle strength and muscle mass. In the 313 patients, dGFR was correlated with age, ALBI and grip strength; CBMM was correlated with body mass index (BMI) and grip strength; and SI was correlated with BMI and grip strength. In patients evaluated with CT, the correlation coefficients for CBMM and SI with SM were 0.804 and 0.293, respectively. Thus, CBMM and SI were associated with sarcopenia. The relationship between dGFR and ALBI does not differ with different grades of CrGFR-based chronic kidney disease (CKD). dGFR is a marker of liver damage and muscle strength regardless of CKD. CBMM and SI are markers for sarcopenia in liver disease., Biomedical Reports, 12(3), pp.89-98; 2020

Highlights • We experienced a an extremely rare anomaly of the right superior PV. • Contrast-enhanced three-dimensional CT (3D-CT) showed that the right superior PV ran abnormally between the right main pulmonary artery (PA) and the right main bronchus. • The anomaly reported in the present case has been reported in only one case report., Introduction Although there are a lot of variations of pulmonary veins (PVs) including dangerous type that could cause serous complications during the surgery, limited information has been reported about these variations. We have experienced an extremely rare anomaly of the right superior PV. Presentation of case A 74-year-old man patient with right lung cancer visited our hospital. Chest computed tomography (CT) revealed a pulmonary nodule in the right lower lobe. Contrast-enhanced three-dimensional CT (3D-CT) showed that the right superior PV ran abnormally between the right main pulmonary artery (PA) and the right main bronchus. We performed right lower lobectomy and systematic nodal dissection. The operative findings confirmed that the right superior PV ran abnormally same as 3D-CT. Discussion In most reported cases, anomalous PVs pass behind the right bronchi or into the roof of the left atrium. The anomaly reported in the present case has been reported in only one case report. This case suggests that the space between the right main PA and the right main bronchus is not always safe for dissection. Conclusion Preoperative 3D-CT is useful for avoiding unexpected bleeding.

Objectives We assessed the relation between coronary plaque composition and angiographic calcification by using virtual histology intravascular ultrasound (VH-IVUS). Background The plaque vulnerability according to angiographic calcification is unclear. Methods Subjects were 140 consecutive patients (145 lesions) undergoing VH-IVUS before percutaneous coronary intervention. Subjects were divided into 4 groups: no calcification group (n = 27), spotty group (n = 65) that had calcium deposits under 90° in grayscale IVUS, intermediate group (n = 37) had calcium deposits with 90° or more and under 180°, and extensive group (n = 16) had calcium deposits with 180° or more. Results The number of VH thin-cap fibroatheromas in spotty group was significantly larger than no calcification group, intermediate group, and extensive group (0.66 ± 0.71 vs 0.22 ± 0.42 [P

Introduction We herein describe a rare case of a pulmonary arteriovenous fistula (PAVF). Presentation of case The patient was a 20-year-old asymptomatic female, admitted to our hospital because of an abnormal shadow in the right lung field on chest X-rays. Chest computed tomography (CT) revealed two nodules with well-defined margins in the right upper and lower lobes. Contrast-enhanced three-dimensional CT (3D-CT) revealed two enhanced solitary lung nodules which were connected with linear structures suggestive of feeding arteries and drainage veins, respectively. Based on these findings, we made a preoperative diagnosis of PAVF. We performed partial pulmonary resection of the right upper and lower lobes by video-assisted thoracoscopic surgery (VATS). The histopathological findings revealed small and medium-sized vascular channels composed of arteries with mild and irregularly thickened muscle walls and juxtaposed or seemingly anastomosing dilated veins. Based on these findings, a diagnosis of PAVF was confirmed. The patient had an uneventful postoperative course. Discussion A PAVF is often associated with various complications, and pregnancy could be a risk factor for these complications because of the increase in the shunt fraction. Females with known PAVF should be maximally treated prior to becoming pregnant as complications of PAVF during pregnancy can have devastating consequences. Therefore, we thought that treatment should be recommended in this case in the event she might later choose to become pregnant. Conclusion Surgical resection using VATS for a limited number of ipsilateral isolated pulmonary arteriovenous fistulae is recommended due to its safety, low recurrence and low mortality rate.

Aim: The aim of this study was to examine cancer and bleeding in atrial fibrillation patients administered with dabigatran. Materials & methods: This study enrolled 509 consecutive nonvalvular atrial fibrillation patients who received dabigatran. The mean administration period was 14.8 ± 15.7 months. We investigated the prevalence and new development of cancers. Further, the relation between cancer and adverse events was evaluated. Results: In the 509 patients, major bleeding occurred in 2.6% and dyspepsia in 8.4%. Further, 16.9% patients had a history of cancer and 3.9% developed new cancers. These adverse events developed in 45% patients who developed new cancers. The cancer (hazard ratio: 6.30; p = 0.003) was a significant predictor of major bleeding. Conclusion: Bleeding was associated with the presence of cancer.

Engineered primary hepatocytes, including co-cultured hepatocyte sheets, are an attractive to basic scientific and clinical researchers because they maintain liver-specific functions, have reconstructed cell polarity, and have high transplantation efficiency. However, co-culture conditions regarding engineered primary hepatocytes were suboptimal in promoting these advantages. Here we report that the hepatocyte morphology and liver-specific function levels are controlled by the normal human diploid fibroblast (TIG-118 cell) layer cell density. Primary rat hepatocytes were plated onto TIG-118 cells, previously plated 3 days before at 1.04, 5.21, and 26.1×103 cells/cm2. Hepatocytes plated onto lower TIG-118 cell densities expanded better during the early culture period. The hepatocytes gathered as colonies and only exhibited small adhesion areas because of the pushing force from proliferating TIG-118 cells. The smaller areas of each hepatocyte result in the development of bile canaliculi. The highest density of TIG-118 cells downregulated albumin synthesis activity of hepatocytes. The hepatocytes may have undergone apoptosis associated with high TGF-β1 concentration and necrosis due to a lack of oxygen. These occurrences were supported by apoptotic chromatin condensation and high expression of both proteins HIF-1a and HIF-1b. Three types of engineered hepatocyte/fibroblast sheets comprising different TIG-118 cell densities were harvested after 4 days of hepatocyte culture and showed a complete cell sheet format without any holes. Hepatocyte morphology and liver-specific function levels are controlled by TIG-118 cell density, which helps to design better engineered hepatocytes for future applications such as in vitro cell-based assays and transplantable hepatocyte tissues.

INTRODUCTION While hypervascular lesions in the lung are known to mimic pulmonary arteriovenous malformation (PAVM), here we report a rare case of lung granuloma mimicking PAVM, on which video-assisted thoracic surgery (VATS) was performed. PRESENTATION OF CASE A 76-year-old woman without any symptom was admitted to our hospital because of abnormal shadow in the left lung field on chest X-ray. A 20 mm × 14 mm nodule with well-defined margins and smooth contours in the left upper segment was detected in her chest computed tomography (CT). Contrast-enhanced three-dimensional CT (3D-CT) revealed an enhanced solitary lung nodule, which was connected with linear structures suggestive of feeding artery and drainage vein. Thus, we made a preoperative diagnosis of PAVM by performing partial pulmonary resection by VATS. Intraoperatively, elastic hard nodule was palpable in the left upper segment and bruit was not convincing. Histopathological findings revealed multiple foci of coagulative necrosis surrounded by epithelioid cell granuloma containing Langhans-type multinucleated giant cells, involving the medium-sized blood vessels in the pulmonary parenchyma. Abnormal vascular structures, such as PAVM were not convincing. Based on these findings, a diagnosis of left lung granuloma was made. DISCUSSION Preoperatively, it was difficult to distinguish the left lung granuloma from PAVM, because hypervascular lesion, such as inflammatory changes can present as strongly enhanced nodules after injection of contrast material. CONCLUSION Surgical approach seems appropriate, not only for the purpose of diagnosis, but also for the safety in treatment of a PAVM.

Although oral amiodarone (AMD) has been used for the management of atrial fibrillation (AF), serious complications such as interstitial pneumonia (IP) occur very occasionally. We evaluated which factors were associated with the development of IP under the long-term administration of AMD in patients with refractory AF.This study included 122 consecutive patients (65.8 ± 11.4 years, mean body mass index [BMI] of 23.2 ± 4.3 kg/m(2)) who orally received AMD to inhibit AF between January 2004 and December 2013. Administration of AMD was begun at 400 mg daily as a loading dose, and was continued at a dosage of 50-400 mg daily after the initial loading phase, determined by the control of the arrhythmias and occurrence of side-effects. The clinical factors were compared between the patients with and without adverse effects, especially IP.During an average follow-up period of 49.2 ± 28.2 months, 53 patients (43.4%) were determined to have converted and maintained sinus rhythm. In contrast, adverse effects were detected in 46 patients (37.7%) with AMD. IP occurred in 8 patients (6.6%), thyrotoxicosis in 35 (28.7%), and others in 5 (4.1%). Four (50.0%) out of 8 patients complicated with IP had obesity (BMI > 27 kg/m(2)). Among the clinical factors, only obesity was significantly associated with the development of IP (P = 0.026).In patients with refractory AF, AMD had an antiarrhythmic effect with long-term administration, but greater adverse effects were also observed. Obesity was the most significant factor associated with the development of IP.

Although cell sheet technology has recently been developed for use in both animal experiments and in the clinical setting, it remains unclear whether transplanted hepatocyte sheets improve the liver function in vivo. Radiation-induced liver damage (RILD) combined with partial hepatectomy (PH) has been reported to suppress the proliferation of host hepatocytes and induce critical liver failure. The aim of this study was to improve the liver function in the above-mentioned diseased rat model (RILD + PH) using multilayered hepatocyte sheet transplantation. In this study, we used Fischer rats as a donor for primary hepatocytes and dermal fibroblast isolation. Cocultured multilayered hepatocyte sheets were generated by disseminating hepatocytes onto fibroblasts cultured beforehand on temperature-responsive culture dishes. Four cell sheets were transplanted into the recipient rats subcutaneously. Prior to transplantation, RILD (50 Gy) with 2/3PH was induced in the recipients. The same model was applied in the control group without transplantation. The serum was collected each week. The rats in both groups were sacrificed at 2 months after transplantation for the histological analysis. Consequently, the serum albumin concentrations were significantly higher in the transplant group than in the control group (54.3 ± 9.6 vs. 32.7 ± 5.7 mg/ml; p < 0.01) after 2 months and comparable to the serum albumin levels in the normal rats (58.1 ± 6.4 mg/ml). In addition, treatment with the transplanted sheets significantly improved the survival rate (57% vs. 22%, p < 0.05), and the hepatocyte sheets showed the storage of albumin, glycogen, and bile canaliculus structures. Some hepatocytes and fibroblasts were positive for Ki-67, and vascularization was observed around the cell sheets. Transplanted multilayered hepatocyte sheets can survive with additional proliferative activity, thereby maintaining the liver function in vivo for at least 2 months, providing metabolic support for rats with RILD.

We assessed the relation between coronary plaque composition and angiographic calcification by using virtual histology intravascular ultrasound (VH-IVUS).The plaque vulnerability according to angiographic calcification is unclear.Subjects were 140 consecutive patients (145 lesions) undergoing VH-IVUS before percutaneous coronary intervention. Subjects were divided into 4 groups: no calcification group (n = 27), spotty group (n = 65) that had calcium deposits under 90° in grayscale IVUS, intermediate group (n = 37) had calcium deposits with 90° or more and under 180°, and extensive group (n = 16) had calcium deposits with 180° or more.The number of VH thin-cap fibroatheromas in spotty group was significantly larger than no calcification group, intermediate group, and extensive group (0.66 ± 0.71 vs 0.22 ± 0.42 [P 0.01], 0.32 ± 0.48 [P 0.05], 0.13 ± 0.34 [P 0.01], respectively). Spotty group without angiographic calcification had significantly larger %necrotic core than with angiographic calcification (24.5 ± 6.7% vs 19.9 ± 7.2%, P 0.05). Intermediate group without angiographic calcification had significantly larger necrotic core area than with angiographic calcification (2.5 ± 0.9 mm(2) vs 1.7 ± 0.9 mm(2) , P 0.05). Extensive group with angiographic calcification had significantly larger %dense calcium than without angiographic calcification (18.3 ± 4.0% vs 13.4 ± 4.4%, P 0.05).Lesions with spotty calcification was highly vulnerable in VH-IVUS. Spotty or intermediate plaque calcification without angiographic calcification was more vulnerable than those with angiographic calcification. Extensive plaque calcification with angiographic calcification had more dense calcium than those without angiographic calcification.

Transport receptors of the importin beta family continuously shuttle between the nucleus and cytoplasm. We previously reported that the nuclear export of importin beta involves energy-requiring step(s) in living cells. Here, we show that the in vitro nuclear export of importin beta also requires energy input. Cytosol, depleted of ATP-binding proteins, did not support the sufficient nuclear export of importin beta. Further purification revealed that the active component in the absorbed fraction was a 70-kD heat shock cognate protein (hsc70). The addition of recombinant hsc70, but not an ATPase-deficient hsc70 mutant, to the depleted cytosol restored the export activity. In living cells, depletion of hsc70 caused the significant nuclear accumulation of importin beta. These effects of hsc70 were observed in the nuclear export of importin beta, but also for other import receptors, transportin and importin alpha. These results suggest that hsc70 broadly modulates nucleocytoplasmic transport systems by regulating the nuclear export of receptor proteins.

beta-Catenin is an example of a typical molecule that can be translocated bidirectionally through nuclear pore complexes (NPCs) on its own in a facilitated manner. In this work the nuclear import and export of beta-catenin were examined to compare the sequence requirement of this molecule and to determine whether molecular interactions required for its bidirectional NPC passage are distinct or not. Deletion analysis of beta-catenin revealed that armadillo repeats 10-12 and the C terminus comprise the minimum region necessary for nuclear migration activity. Further dissection of this fragment showed that the C terminus tail plays an essential role in nuclear migration. The region of beta-catenin required for export substantially overlapped the region required for import. Therefore, the NPC translocation of beta-catenin is apparently reversible, which is consistent with findings reported previously. However, different translocating molecules blocked nuclear import and export of beta-catenin differentially. The data herein indicate that beta-catenin shows an overlapping sequence requirement for its import and export but that bidirectional movement through the NPC proceeds through distinct molecular interactions.

Background There are very few reliable and valid measures in Japan assessing health-related quality of life (HRQOL) in children with cancer. The present study aimed to develop a Japanese version of the Minneapolis-Manchester Quality of Life Survey of Health Adolescent Form (MMQL-AF), which is a measure for assessing the HRQOL of childhood cancer survivors, and investigate its reliability and validity. Methods Participants were 141 children with cancer who had been off therapy for more than one year and 183 healthy controls. The reliability and internal consistency of the measure were assessed through test-retest methods using Cronbach’s coefficient alpha and intra-class correlation coefficients (ICCs). For validation of the measure, factorial validity, concurrent validity using the Japanese version of PedsQL 4.0 Generic Core Scales (PedsQL-J), and discriminant validity using comparisons between children with cancer and healthy controls were investigated. Results Of the 46 items in the original version, 44 items were determined to comprise the Japanese version of the MMQL-AF. Cronbach’s coefficient alphas for each subscale were high ranging from 0.83 to 0.89. Test-retest reliability ranged between ICC 0.79 to 0.96. Investigation of concurrent validity using the PedsQL-J demonstrated strong correlations in physical functions and moderate correlations for other factors. A significant difference was observed between children with cancer and healthy controls. Conclusions Thus, the Japanese version of the MMQL-AF served as a self-evaluation questionnaire that allowed for practical, comprehensive, and multidimensional measurement of HRQOL specific to childhood cancer survivors.

BACKGROUND To the authors' knowledge, there had been no evidence for the efficacy of psychosocial intervention among Japanese cancer patients. The objective of this study was to determine the effect of a psychosocial group intervention in reducing psychologic distress and enhancing coping in this population in a randomized controlled trial. METHODS The patient selection criteria were age younger than 65 years, lymph node metastasis positive and/or histologic or nuclear Grade 2–3, and surgery undergone within the previous 4–18 months as of the start of the study. We conducted a 6-week, structured, psychosocial group intervention. The intervention consisted of health education, coping skills training, stress management, and psychologic support. Subjects were assessed for psychologic distress and coping by administering the Profile of Mood States (POMS), Mental Adjustment to Cancer (MAC) scale, and Hospital Anxiety and Depression (HADS) scale at the baseline, at 6 weeks, and at 6 months. RESULTS Fifty (33%) of the 151 patients participated and were randomized, and 46 (30%) completed the study. The experimental group had significantly lower scores than the controls for total mood disturbance and significantly higher scores for vigor on the POMS, and significantly higher scores for fighting spirit on the MAC at the end of the 6-week intervention. These improvements were sustained over 6 months of follow-up. CONCLUSIONS The results of this study suggest that a short term psychosocial group intervention produces significant long term improvement in the quality of life of Japanese patients with primary breast carcinoma. Cancer 2000;89:1026–36. © 2000 American Cancer Society.

This paper examines the applicability of psychosocial group intervention for Japanese patients with primary breast cancer. The study included two phases. First, we examined the applicability for Japanese patients of an intervention model developed in a Western country. The model, based on the work of Fawzy and Fawzy (1994) on a structured psychosocial group intervention for cancer patients, is a series of six 1.5-h sessions that incorporate health education, coping-skills training, relaxation training and psychological support. Second, we formulated a Japanese version of the intervention model by modifying areas identified as inappropriate by participants in the first-phase study. We then evaluated this by conducting sessions of the modified model with 44 additional breast cancer patients. Of the ten participants in the first-phase pilot study, three (30%) dropped out and several inappropriate areas were reported. The areas requiring significant change were the provision of medical information and communication style with family members and doctors. No participants dropped out of the modified version, and very few found any program areas to be inappropriate. The findings suggests that psychosocial group intervention is applicable for Japanese breast cancer patients when the model accounts for cultural differences.

Subcutaneous liver tissue construction is an attractive and minimally invasive approach used to overcome the chronic shortage of donor livers for the curative treatment of hepatic failure. However, graft failure occurs frequently due to lack of blood vessels. In this study, we describe a subcutaneous human liver reconstruction approach allowing for rapidly vascularized grafts by transplanting engineered hepatocyte/fibroblast sheets (EHFSs).Human primary hepatocytes were isolated and purified from surgically resected human liver tissues by the collagenase perfusion method. EHFSs were fabricated using temperature-responsive culture dishes (TRCDs) (UpCell; CellSeed, Tokyo). The hepatocytes were plated onto a confluent layer of normal human dermal fibroblasts (TIG-118 cells). After 4 days in culture, EHFSs were harvested and transplanted subcutaneously into immunodeficient mice. The expression levels of angiogenic factors in vitro, liver-specific functions and structures in vivo, and therapeutic potential of serious liver diseases were evaluated.EHFSs exhibited significantly higher synthesis rates of VEGF, TGF-b1, and HGF than the hepatocyte-only sheets (HSs) from 1 to 3 days in culture. This result indicate the possibility of using a one-step subcutaneous hepatocyte transplantation procedure without a pre-transplant vascularization step such as implanting a FGF-releasing device. The transplanted EHFSs were laminated and formed a vascularized subcutaneous human liver tissues (VSLTs). The VSLTs had liver-specific features such as glycogen stores and albumin, A1AT, and coagulation factor IX syntheses. The aggregated hepatocytes formed several linear structures. Furthermore, subacute hepatic failure model mice (TK-NOG mice) with VSLT were alive at least 7 weeks after liver damage.The present study describes a new approach for vascularized human liver organogenesis under mouse skin. This approach could prove valuable for establishing novel minimally invasive cell therapies for liver diseases.

To cover the receptive field completely and non-redundantly, neurons of certain functional groups arrange tiling of their dendrites. In Drosophila class IV dendrite arborization (da) neurons, the NDR family kinase Tricornered (Trc) is required for homotypic repulsion of dendrites that facilitates dendritic tiling. We here report that Sin1, Rictor, and target of rapamycin (TOR), components of the TOR complex 2 (TORC2), are required for dendritic tiling of class IV da neurons. Similar to trc mutants, dendrites of sin1 and rictor mutants show inappropriate overlap of the dendritic fields. TORC2 components physically and genetically interact with Trc, consistent with a shared role in regulating dendritic tiling. Moreover, TORC2 is essential for Trc phosphorylation on a residue that is critical for Trc activity in vivo and in vitro. Remarkably, neuronal expression of a dominant active form of Trc rescues the tiling defects in sin1 and rictor mutants. These findings suggest that TORC2 likely acts together with the Trc signalling pathway to regulate the dendritic tiling of class IV da neurons, and thus uncover the first neuronal function of TORC2 in vivo.

Heat-shock induces a strong stress response and modifies all aspects of cellular physiology, which involves dynamic changes in the nucleocytoplasmic distributions of a variety of proteins. Many distinct nucleocytoplasmic transport pathways exist in eukaryotic cells, but how a particular transport pathway is regulated under different cellular conditions remains elusive. The finding of this study indicate that conventional nuclear import, which is mediated by importin alpha/beta, is down-regulated, while the nuclear import of 70 kD heat-shock cognate protein is up-regulated in heat-shock cells. Among the factors involved in the mediation of the conventional nuclear import, significant levels of importin alpha accumulate in the nucleus in response to heat-shock. An analysis of the behaviour of importin alpha with fluorescence recovery after photobleaching and fluorescence loss in photobleaching studies show that nuclear importin alpha becomes less mobile and its nucleocytoplasmic recycling is impaired in heat-shock cells. These data coincided well with biochemical and cytological studies. Our present data show that heat-shock induces the nuclear accumulation, nuclear retention, and recycling inhibition of importin alpha, resulting in the suppression of conventional nuclear import. This suggests a new regulatory mechanism for the adaptation of cells to environmental changes, such as heat-shock.

Background. Despite significant communication gaps between patients and physicians, there has been little effort to initiate and evaluate teaching programs. We investigated whether a communication skills training (CST) could be effectively conducted for Japanese oncologists. Methods. Fifty-eight oncologists participated in the CST. We evaluated the program by measuring participant-rated confidence for communication with patients, burnout, and satisfaction of participants. Results. Immediately and at 3 months after CST, confidence in communication increased significantly compared with before. The providers' emotional-exhaustion 3 months after the workshop, however, worsened. The participants' satisfaction level with the program was high. Conclusions. The CST is feasible for Japanese oncologists, but it needs to be modified to reduce emotional-exhaustion. J Cancer Educ. 2003; 18:194-201.

Cancer patients face a variety of problems and undergo psychological turbulence during the clinical course of their disease. In particular, problems related to treatment, such as chemotherapy, can pose a great burden and place the patients in an unstable status, involving both anxiety and expectation related to problems faced in daily life and the unreliability of the therapeutic effects. To cope with the various psychological problems experienced by cancer patients, individual counseling, group therapy, and behavioral therapy, including progressive muscle relaxation training and autonomic training, are employed, depending on the situation of each individual patient. Clinical psychologists participating in cancer treatment need a basic knowledge and understanding of the pathological characteristics of cancer, methods of treatment, and the characteristic clinical course of various cancers, in order to be in close contact and maintain communication with physicians, nurses, and other medical staff, and to provide the support demanded by the patients and their family through a variety of approaches.

Background. The components of psychoeducational interventions which are effective in reducing psychological distress are not well known. Objectives. To examine whether increasing satisfaction with information provided by psychoeducational interventions is associated with reducing psychological distress. Patients and method. The subjects were consecutively selected from breast cancer outpatients surgically treated at the National Cancer Center Hospital East in Japan. We conducted a 6-week psychoeducational intervention in 44 women with primary breast cancer. Satisfaction with information was assessed using the Visual Analogue Scale, and a hierarchical regression analysis was used to investigate the relationship between psychological distress and patient satisfaction with the information provided. Results. Available data were obtained in 41 patients. At 6 months after intervention, increased satisfaction with information about breast cancer (p=0.02) and methods for coping with cancer (p=0.04) were significantly associated with lower total mood disturbance scores. Conclusion. The results suggest that offering appropriate medical and psychological information in psychoeducational interventions might increase patient satisfaction with information, resulting in lower psychological distress.

Purpose/objectives To examine the effects of a psychosocial group intervention on loneliness and social support in Japanese women with breast cancer. Design Secondary analysis of a randomized, controlled trial. Setting A breast cancer outpatient area of a National Cancer Center hospital in Japan. Sample 50 women who were less than 65 years old, were diagnosed with primary breast cancer, and had undergone surgery within 4-18 months of the start of the study. Methods Data were collected as part of a trial of an intervention. The investigators conducted a six-week group intervention consisting of health education, coping skills training, stress management, and psychological support. Subjects completed the revised University of California, Los Angeles, Loneliness Scale and a social support questionnaire at baseline, six weeks, and six months. Main research variables Loneliness, number of confidants, satisfaction with confidants, and satisfaction with mutual aid. Findings Fifty (33%) of the 151 invited patients participated and were randomized to either experimental (n = 25) or control (n = 25) groups, and 23 (92%) in each group completed the study. The experimental group had significantly lower scores than the control group for loneliness and significantly higher scores for the number of confidants, satisfaction with confidants, and satisfaction with mutual aid over the six-month study period. Conclusions This intervention is beneficial for Japanese patients with breast cancer experiencing loneliness and inadequate social support. Implications for nursing The program can be used as an effective support for Japanese patients with cancer to manage their psychosocial concerns associated with illness.

Importin-beta is a nuclear transport factor which mediates the nuclear import of various nuclear proteins. The N-terminal 1-449 residue fragment of mouse importin-beta (impbeta449) possesses the ability to bidirectionally translocate through the nuclear pore complex (NPC), and to bind RanGTP. The structure of the uncomplexed form of impbeta449 has been solved at a 2.6 A resolution by X-ray crystallography. It consists of ten copies of the tandemly arrayed HEAT repeat and exhibits conformational flexibility which is involved in protein-protein interaction for nuclear transport. The overall conformation of the HEAT repeats shows that a twisted motion produces a significantly varied superhelical architecture from the previously reported structure of RanGTP-bound importin-beta. These conformational changes appear to be the sum of small conformational changes throughout the polypeptide. Such a flexibility, which resides in the stacked HEAT repeats, is essential for interaction with RanGTP or with NPCs. Furthermore, it was found that impbeta449 has a structural similarity with another nuclear migrating protein, namely beta-catenin, which is composed of another type of helix-repeated structure of ARM repeat. Interestingly, the essential regions for NPC translocation for both importin-beta and beta-catenin are spatially well overlapped with one another. This strongly indicates the importance of helix stacking of the HEAT or ARM repeats for NPC-passage.

Cell sheet engineering is attracting attention from investigators in various fields, from basic research scientists to clinicians focused on regenerative medicine. However, hepatocytes have a limited proliferation potential in vitro, and it generally takes a several days to form a sheet morphology and multi-layered sheets. We herein report our rapid and efficient technique for generating multi-layered human hepatic cell (HepaRG® cell) sheets using pre-cultured fibroblast monolayers derived from human skin (TIG-118 cells) as a feeder layer on a temperature-responsive culture dish. Multi-layered TIG-118/HepaRG cell sheets with a thick morphology were harvested on day 4 of culturing HepaRG cells by forceful contraction of the TIG-118 cells, and the resulting sheet could be easily handled. In addition, the human albumin and alpha 1-antitrypsin synthesis activities of TIG-118/HepaRG cells were approximately 1.2 and 1.3 times higher than those of HepaRG cells, respectively. Therefore, this technique is considered to be a promising modality for rapidly fabricating multi-layered human hepatocyte sheets from cells with limited proliferation potential, and the engineered cell sheet could be used for cell transplantation with highly specific functions., PLoS ONE, 8(7), e70970; 2013

Background A persistent sciatic artery is a rare congenital anomaly, and an arteriovenous malformation arising on persistent sciatic vessels is extremely rare. Methods This report presents the case of a 30-year-old female with persistent sciatic vessels complicated with an arteriovenous malformation in the right buttock. It was surgically inaccessible, and a three-staged transcatheter embolization using 20% N- butyl-cyanoacrylate/80% lipiodol was performed. Results The arteriovenous malformation was shown to have been extinguished by multidetector computed tomography. Conclusions This report presents the first case of persistent sciatic vessels complicated with an arteriovenous malformation treated by transcatheter embolization.

Rationnelle L’artere sciatique persistante est une anomalie congenitale rare et la survenue d’une malformation arterio-veineuse sur vaisseaux sciatiques persistants est extremement rare. Methodes Cet article presente le cas d’une patiente de 30 ans ayant des vaisseaux sciatiques persistants compliques d’une malformation arterio-veineuse de la fesse droite. Elle etait chirurgicalement inaccessible et une embolisation en trois etapes utilisant un melange de 20% N- butyl-cyanoacrylate/80% lipiodol a ete effectuee. Resultats L’angioscanner multi barrettes a montre la disparition de la malformation arterio-veineuse. Conclusions Cet article presente le premier cas de malformation arterio-veineuse localisee sur des vaisseaux sciatiques persistants et traitee par embolisation percutanee.