Bone density estimation using tissue heat capacity.

Osteoporosis onset is relatively asymptomatic, the condition often being identified only once a significant fracture occurs, leading to a potentially serious prognosis. Currently, early identification of osteoporosis is complicated by the difficulty in measuring bone density without using x-ray absorptiometry or quantitative ultrasound, so a simpler method for estimating bone density is needed. Given that bone is reported to have a lower specific heat than other tissues, we investigated the possibility of estimating bone density using this difference in tissue thermal properties. The tibia medial surface (shin) and medial malleolus (ankle) of 68 healthy volunteers were cooled using an ice bag, and skin surface temperatures and heat flow were recorded. These measurements were then used to calculate the heat energy transferred per unit temperature. Bone density was estimated by quantitative ultrasound using the T score OSISD, which is the participant's osteo sono-assessment index (OSI) compared to the average OSI of young adults. The heat energy transfer per unit temperature at the shin, but not the ankle, showed a significant negative correlation with T score OSISD (r = -0.413, p = 0.001). Multiple regression analysis showed that heat energy transfer per unit temperature at the shin was a significant predictor of T score OSISD, along with age and height. These results show that tissue thermal property measurements are useful for estimating bone density.

Quantitative Assessment of the Heat Transfer Capacity of Ice Bags and their Cooling Effects on the Skin Surface and Core Temperature.

Ice bags are frequently used in medical care settings for pain relief, comfort, and in some cases, whole-body cooling. This study quantifies heat energy transfer capacity of ice bags and evaluates their cooling effects on body temperature. Forty-eight healthy adults in their 20s were recruited. An ice bag wrapped in two layers of dry towel was applied to the forehead, neck, or palm of each participant for 10 min. The skin surface temperature, heat flow, and core temperature were recorded during the cooling and non-cooling periods, with energy transfer calculated by integrating heat flow over time. Over the non-cooling period, 31.4-53.6 kJ·m-2 of energy was dissipated over 10 min, whereas during the cooling period, the range increased to 180.0-218.7 kJ·m-2 over 10 min. Skin surface temperature decreased by 3.2-5.7°C, whereas core temperature was unchanged. Ice bag use augmented energy transfer by about 150-180 kJ·m-2 over 10 min, but this was insufficient for rapid whole body cooling due to the small skin-surface area in contact with the ice bag. The measured energy transfer indicated that topical ice bag application absorbs insufficient energy to affect core temperature. Quantitative assessment of energy transfer was shown to inform the safe and appropriate use of thermotherapy.

A novel symbiotic relationship between ascidians and a new tunic-boring polychaete (Annelida: Spionidae: Polydora).

Polydora tunicola Abe, Hoshino Yamada, sp. nov., a new spionid species currently considered an obligate symbiont of styelid ascidians, is described based on materials collected from Polycarpa cf. cryptocarpa kroboja (Oka, 1906) and Cnemidocarpa sp. in Izu-Oshima Island and Polycarpa sp. in Wakayama Prefecture, Japan. Polychaeteascidian symbiotic relationships are known only in two syllid species: Myrianida pinnigera (Montagu, 1808) and Proceraea exoryxae Martin, Nygren Cruz-Rivera, 2017. The latter has been the only polychaete known to bore into the tunic of an ascidian. Polydora tunicola sp. nov. is the second known example of a tunic-boring polychaete, which constructs U-shaped burrows in the tunic of the host ascidians. Worms were often concentrated near the host siphons and assumed to use water currents created by the filter-feeding host for suspension feeding. Although the boring mechanism into ascidian tunica is unknown, the plate assay and zymography results consistently detected cellulase activities, suggesting that cellulose digestion may enable the worms to bore into the cellulose-rich ascidian tunics. Polydora tunicola sp. nov. is morphologically similar to P. aura Sato-Okoshi, 1998, P. cornuta Bosc, 1802, P. fusca Radashevsky Hsieh, 2000, P. glycymerica Radashevsky, 1993, P. latispinosa Blake Kudenov, 1978, P. lingulicola Abe Sato-Okoshi, 2020, P. nanomon Orensky Williams, 2009, P. robi Williams, 2000, and P. vulgaris Mohammad, 1972 in having a single median antenna on the caruncle and chaetiger 5 without dorsal superior capillaries but with ventral capillaries. The new species is unique in having a black-rimmed pygidium, distinguishing it from these species. The phylogenetic analyses of the concatenated 18S, 28S, and 16S sequences recovered P. tunicola sp. nov. as the sister species to P. aura within a well-supported clade also including P. lingulicola and P. cf. glycymerica. The bright yellow body color of P. tunicola sp. nov. in life is similar to that of P. aura, however, these two species are distinguished by the former not having modified posterior notochaetae. The symbiotic nature of the association between P. tunicola sp. nov. and styelid ascidians is discussed.

The relationship among factors of organizational justice, organizational citizenship behavior, job satisfaction, and ease of work among Japanese nurses.

AIM: This work is aimed to create a strategy to improve the nurses' working environment. BACKGROUND: As the working-age population is expected to decline in Japan, the maintenance of the nurse workforce is important. In order to create a strategy to improve the nurses' working environment, we studied the relationship among factors of organizational justice (procedural, distributive, and interactional justices), organizational citizenship behavior, job satisfaction, and ease of work. METHODS: A cross-sectional, self-administered questionnaire was distributed to 969 nurses and 322 effective responses were analyzed (effective response rate 33.2%). The questionnaire contained demographic information, ease of work, and three scales for organizational justice, organizational citizenship behavior, and job satisfaction. The factor structure of the scales was studied using exploratory and confirmatory factor analysis. Structural equation modeling was used to investigate the relationship among measurements. The protocol was approved by the ethical committee of the author's university. RESULTS: The final model showed a fair fit to the data (χ2 = 1803.15, df = 1014, p < 0.001, comparative fit index = 0.907, root mean square error of approximation = 0.049). Interactional justice showed the most significant correlation to job satisfaction (r = 0.590). Job satisfaction and ease of work also showed a significant positive correlation (r = 0.696). Distributive justice had a slight negative indirect effect on job satisfaction, whereas procedural justice had no significant effect. CONCLUSION: In order to enhance job satisfaction/ease of work among Japanese nurses, improvement of interactional justice may be the best strategy.

Impact of Parents' Knowledge about the Development of Self-Esteem in Adolescents and Their Parenting Practice on the Self-Esteem and Suicidal Behavior of Urban High School Students in Nepal.

BACKGROUND: Suicide is the third leading cause of death in adolescents worldwide, self-esteem is a strong protective factor, and parents may be able to provide interventions. This cross-sectional study aimed to determine how parents can help enhance their adolescent's self-esteem and prevent suicidal behavior among adolescents in Nepal. METHODS: Self-administered questionnaires were distributed to adolescents aged 13-19 years and their parents at eight high schools in three provinces in Nepal (n = 575 pairs). The data were analyzed using descriptive and inferential statistics (bivariate and multivariate regression analyses). RESULTS: The mean self-esteem score of adolescents according to the Rosenberg Self-Esteem Scale was 16.59, and the prevalence of suicidal behavior was 11.3%. Parent's knowledge about the development of self-esteem in adolescents was significantly positively related to parenting practice (communication, support, positive reinforcement, etc.) (B = 1.0, 95% confidence interval, CI 0.89-1.11) and authoritative parenting style (B = 0.2, 95% CI 0.15-0.25). Parental authoritativeness was positively associated with the self-esteem of their adolescents (B = 0.1, 95% CI 0.01-0.18), while adolescents with authoritarian parents were prone to suicidal risk behavior (adjusted odds ratio, AOR = 1.1, 95% CI 1.0-1.19). CONCLUSION: Counseling to parents based on our findings would be helpful to enhance the self-esteem and prevent suicidal risk behavior in their adolescent children.

Self-esteem, perceived social support, social capital, and risk-behavior among urban high school adolescents in Nepal.

Adolescence is not only characterized by a period of exploration and experimentation but also by vulnerability to risk-behaviors (substance-use, suicidal behavior, and sexual behavior) that can have many negative consequences. Given the lack of studies in Nepal and the variable results from international studies on the association of self-esteem, perceived social support (PSS), and social capital (SC) with risk behaviors, this study aimed to assess the role of these factors by specifying different sources of PSS (family, friends, and others) and SC (family, school, and neighbors), and controlling for demographic, socioeconomic-status (SES), family, and school related factors. A total of 943 adolescents (grades 9-11) in 8 schools from 3 provinces in Nepal participated in the study, and were selected by multi-stage, cluster, random sampling. Data were collected through a self-administered questionnaire (response rate; 91.9%). Multivariate logistic regression analysis (<0.05 significance) revealed that family SC (OR = 0.83) and PSS from family (OR = 0.95) were negatively associated with substance-use. Self-esteem (OR = 0.90), family and school SC (OR = 0.80 and 0.91, respectively), and PSS from family and friends (OR = 0.95 and 0.96, respectively) were protective against suicidal risk. None of the independent variables showed a preventive association with sexual behavior, but self-esteem was positively associated (OR = 1.11). Therefore, to improve the likelihood of adolescents becoming healthy adults, family and school level interventions to enhance self-esteem, PSS, and SC are helpful in protecting them against substance use and suicidal behavior. On the other hand, adolescents with high self-esteem are at greater risk for inappropriate sexual behavior and should therefore be monitored.

Relationship among independence of daily living, human relationships, and preparation for bereavement among healthy elderly Japanese people.

BACKGROUND: Given Japan's rapidly ageing society, an increasing number of elderly people live in their communities with mutual support after the death of their spouse. The purpose of this study is to clarify the relationship among independence of daily living, human relationships, and preparation for bereavement. METHODS: An anonymous, self-administered questionnaire was given to 864 community-dwelling elderly people aged 65 and older who attended an Elderly Citizens' Welfare Study Group. A total of 404 responses (effective response ratio: 46.8%) were analyzed. Their mean ± SD age was 75.6 ± 5.1 years. The purpose of the questionnaire was to obtain demographic information as well as information about three scales: independence of daily living, human relationships, and preparation for bereavement. The factor structure of the scales was studied by using exploratory and confirmatory factor analysis. Structural equation modelling was used to investigate the relationship among independence of daily living, human relationships, and preparation for bereavement. This study's protocol was approved by the Ethics Committee of Okayama Prefectural University. RESULTS: Factor analysis indicated a three-factor second-order factor model for independence of daily living and human relationships and a one-factor model for preparation for bereavement. Structural equation modelling showed that independence of daily living was significantly correlated with human relationships (r = 0.261, P < 0.001), and human relationships was significantly correlated with preparation for bereavement (r = 0.295, P < 0.001). There was no significant direct correlation between the independence of daily living and preparation for bereavement. CONCLUSIONS: Encouraging elderly people to form good human relationships may help their preparation for bereavement. Further studies are required to determine whether this actually attenuates difficulties after bereavement.

Tapping enhances vasodilation for venipuncture even in individuals with veins that are relatively difficult to palpate.

INTRODUCTION: This study evaluated whether tapping enhances vasodilation in individuals with veins that are relatively difficult to palpate. MATERIALS AND METHODS: Twenty participants (4 men and 16 women, aged 19-22 years) with cutaneous veins that were relatively difficult to palpate even after tourniquet application were recruited. A crossover trial with/without tapping (10 times in 5 s) was performed under tourniquet inflation on the upper arm. Vasodilation was evaluated by venous cross-sectional area, depth of the vein, and elevation of the overlying skin by ultrasonography. Venous palpation scores were also measured. The degree of improvement was estimated by simulation. RESULTS: In total, 60% of participants "sometimes" or "often" experienced unsuccessful venipuncture. After the tapping procedure, the venous cross-sectional area significantly increased (14.6 ± 9.12 mm2 for control and 15.2 ± 9.79 mm2 for tapping) and venous depth significantly decreased (4.57 ± 2.31 mm for control and 4.23 ± 2.41 mm for tapping). A simulation study using these values suggested that tapping increased the longitudinal and crosswise successful ranges of venipuncture by 5-6%. CONCLUSIONS: Tapping in this study enhanced the vasodilation of cutaneous veins that are relatively difficult to palpate. The effectiveness of various vasodilation methods may be compared through the estimation of improvement.

Identification of possible hypoxia sensor for behavioral responses in a marine annelid, Capitella teleta.

Hypoxia often occurs in summer and causes deleterious effects on marine benthic animals. A marine annelid, Capitella teleta, is tolerant to hypoxia, as shown by the fact that it inhabits organically polluted areas, where severe hypoxia is often observed. To understand how this species adapts to the environment, we focused on its hypoxia sensor, and we showed that TRPAbasal was a possible contributor to hypoxia detection in C. teleta To examine the involvement of TRPA1 in the response of C. teleta to hypoxia, we exposed C. teleta to hypoxic water with or without a TRPA1-specific inhibitor, A-967079. Hypoxic stimulation induced escape behavior in C. teleta from the sediment, and this behavior was suppressed by the inhibitor. The cloned TRPA gene from C. teleta was phylogenetically categorized into TRPAbasal, and contains an oxygen-dependent degradation domain, which is important for the detection of hypoxia. Whole-mount in situ hybridization analysis showed that the gene was transcribed in the prostomium, where sensing functions are localized. These results suggested that the worm has a hypoxia-sensing system possibly utilizing CtTRPAbasal, and this system contributes to expanding the organism's niches in hypoxic environments by detecting whether hypoxia exceeds a level that would imperil its survival.

Glutathione accelerates osteoclast differentiation and inflammatory bone destruction.

Chronic inflammation associated with bone tissues often destructs bones, which is essentially performed by osteoclasts in the presence of immunoregulatory molecules. Hence, regulating osteoclastogenesis is crucial to develop therapeutics for bone-destructive inflammatory diseases. It is believed that reactive oxygen species (ROS) are involved in receptor activator of NF-κB (RANK) ligand (RANKL)-induced osteoclast differentiation, and, therefore, glutathione (GSH), the most abundant endogenous antioxidant, suppresses osteoclast differentiation and bone resorption by RANKL. Interestingly, GSH also contributes to inflammatory responses, and the effects of GSH on osteoclast differentiation and bone destruction under inflammatory conditions have not yet been determined. Here, we investigated how GSH affects inflammatory cytokine-stimulated osteoclast differentiation in vitro and in a mouse model of inflammatory bone destruction. We found that GSH significantly promoted TNFα-stimulated osteoclast formation, while an inhibitor of GSH synthesis, buthionine sulfoximine, suppressed it. GSH facilitated the nuclear localisation of the nuclear factor of activated T cells c1 (NFATc1) protein, a master regulator of osteoclastogenesis, as well as the expression of osteoclast marker genes in a dose-dependent manner. N-acetylcysteine, a substrate of GSH synthesis, also stimulated osteoclast formation and NFATc1 nuclear localisation. GSH did not suppress cell death after osteoclast differentiation. In mouse calvaria injected with lipopolysaccharide, GSH treatment resulted in a fivefold increase in the osteolytic lesion area. These results indicate that GSH accelerates osteoclast differentiation and inflammatory bone destruction, suggesting GSH appears to be an important molecule in the mechanisms responsible for inflammatory bone destruction by osteoclasts.

Highly sensitive avoidance plays a key role in sensory adaptation to deep-sea hydrothermal vent environments.

The environments around deep-sea hydrothermal vents are very harsh conditions for organisms due to the possibility of exposure to highly toxic compounds and extremely hot venting there. Despite such extreme environments, some indigenous species have thrived there. Alvinellid worms (Annelida) are among the organisms best adapted to high-temperature and oxidatively stressful venting regions. Although intensive studies of the adaptation of these worms to the environments of hydrothermal vents have been made, little is known about the worms' sensory adaptation to the severe chemical conditions there. To examine the sensitivity of the vent-endemic worm Paralvinella hessleri to low pH and oxidative stress, we determined the concentration of acetic acid and hydrogen peroxide that induced avoidance behavior of this worm, and compared these concentrations to those obtained for related species inhabiting intertidal zones, Thelepus sp. The concentrations of the chemicals that induced avoidance behavior of P. hessleri were 10-100 times lower than those for Thelepus sp. To identify the receptors for these chemicals, chemical avoidance tests were performed with the addition of ruthenium red, a blocker of transient receptor potential (TRP) channels. This treatment suppressed the chemical avoidance behavior of P. hessleri, which suggests that TRP channels are involved in the chemical avoidance behavior of this species. Our results revealed for the first time hypersensitive detection systems for acid and for oxidative stress in the vent-endemic worm P. hessleri, possibly mediated by TRP channels, suggesting that such sensory systems may have facilitated the adaptation of this organism to harsh vent environments.

Effects of Postprandial Body Position on Gastrointestinal Motility, the Autonomic Nervous System and Subjective Comfort.

We examined postprandial body positions' effects on gastrointestinal motility, the autonomic nervous system and subjective comfort, i.e., whether lowering the head after a meal is beneficial for gastrointestinal motility and the prevention of pressure ulcer. We examined 10 healthy subjects and compared 3 body positions: (1) Seated upright. (2) Lying on a bed with the head at 60° and knees up by 20° (60° position). (3) Identical to (2) until post-meal; the head was then lowered to 30° (60°-30° position). Gastrointestinal motility was assessed as gastrointestinal sounds measured by sound-editing software. Digital plethysmography assessed autonomic nerve function as heart rate variability. The pressure ulcer risk was estimated as subjective comfort/discomfort using a visual analog scale. Gastrointestinal sounds increased post-meal. The 60°-30° position showed the highest number of sounds and longest cumulative sound duration. Post-meal, sympathetic activation was suggested in the 60° position, whereas vagal activity was relatively preserved in the 60°-30° position. The 60°-30° position was the most comfortable, and the 60° position was least comfortable. Lowering the head after a meal is beneficial to augment gastrointestinal motility and decrease the pressure ulcer risk. The 60° head-up position increases the pressure ulcer risk.

Successful management of unresectable small bowel lymphoma with laparoscopy-assisted surgical exclusion of the affected intestine.

The incidence of small bowel lymphoma (SBL) is increasing worldwide. In contrast to resectable SBL, the treatment of unresectable SBL is still contentious. Here, we report a case of unresectable SBL that was treated by laparoscopic exclusion of the affected intestine before systemic chemotherapy was administered. An 84-year-old man was diagnosed with primary SBL involving extranodal dissemination. The patient received prophylactic surgery, namely exclusion of the affected intestine. This therapy diminishes well-known and life-threatening complications, such as perforation, bleeding, and obstruction, which may still occur after chemotherapy, and it makes the administration of chemotherapy safer. In addition, the surgery provides easy access for direct endoscopic observation and biopsy, which are otherwise difficult to perform. Follow-up after two courses of chemotherapy showed that the patient had achieved complete remission. In conclusion, the procedure described here may be an effective strategy for unresectable SBL.

Phytoestrogen Suppresses Efflux of the Diagnostic Marker Protoporphyrin IX in Lung Carcinoma.

One promising method to visualize cancer cells is based on the detection of the fluorescent photosensitizer protoporphyrin IX (PpIX) synthesized from 5-aminolevulinic acid (ALA), but this method cannot be used in cancers that exhibit poor PpIX accumulation. PpIX appears to be pumped out of cancer cells by the ABC transporter G2 (ABCG2), which is associated with multidrug resistance. Genistein is a phytoestrogen that appears to competitively inhibit ABCG2 activity. Therefore, we investigated whether genistein can promote PpIX accumulation in human lung carcinoma cells. Here we report that treatment of A549 lung carcinoma cells with genistein or a specific ABCG2 inhibitor promoted ALA-mediated accumulation of PpIX by approximately 2-fold. ABCG2 depletion and overexpression studies further revealed that genistein promoted PpIX accumulation via functional repression of ABCG2. After an extended period of genistein treatment, a significant increase in PpIX accumulation was observed in A549 cells (3.7-fold) and in other cell lines. Systemic preconditioning with genistein in a mouse xenograft model of lung carcinoma resulted in a 1.8-fold increase in accumulated PpIX. Long-term genistein treatment stimulated the expression of genes encoding enzymes involved in PpIX synthesis, such as porphobilinogen deaminase, uroporphyrinogen decarboxylase, and protoporphyrinogen oxidase. Accordingly, the rate of PpIX synthesis was also accelerated by genistein pretreatment. Thus, our results suggest that genistein treatment effectively enhances ALA-induced PpIX accumulation by preventing the ABCG2-mediated efflux of PpIX from lung cancer cells and may represent a promising strategy to improve ALA-based diagnostic approaches in a broader set of malignancies. Cancer Res; 76(7); 1837-46. ©2016 AACR.

Tapping but not massage enhances vasodilation and improves venous palpation of cutaneous veins.

This paper investigated whether tapping on the median cubital vein or massaging the forearm was more effective in obtaining better venous palpation for venipuncture. Forty healthy volunteers in their twenties were subjected to tapping (10 times in 5 sec) or massage (10 strokes in 20 sec from the wrist to the cubital fossa) under tourniquet inflation on the upper arm. Venous palpation was assessed using the venous palpation score (0-6, with 0 being impalpable). Three venous factors-venous depth, cross-sectional area, and elevation-were also measured using ultrasonography. The venous palpation score increased significantly by tapping but not by massage. Moreover, all 3 venous measurements changed significantly by tapping, while only the depth decreased significantly by massage. The three venous measurements correlated significantly with the venous palpation score, indicating that they are useful objective indicators for evaluating vasodilation. We suggest that tapping is an effective vasodilation technique.

The characteristics of healthy adults with hardly palpable vein--Relations between easy venous palpation and physical factors.

This study aimed to investigate relations between ease of venous palpation and various venous factors, and to elucidate characteristics of hardly palpable veins. Healthy adult volunteers (n = 110) were enrolled. The ease of venous palpation was scored from 0: impalpable to 3: well palpable. Venous factors, namely venous depth, elevation, area and minimal pressure that starts to collapse vein, were measured using an ultrasonography before and after tourniquet inflation at 60 mmHg for 60 s. Tourniquet inflation significantly increased the venous area and venous palpation score. The four venous factors correlated significantly with venous palpation score with the following correlation coefficient: Depth (r = -0.542), Elevation (0.486), area (0.258) and start-to-collapse pressure (-0.220). The characteristics of hardly palpable veins were small size, deep location and little elevation. Although vasodilatation facilitated venous palpation, venous depth and elevation were also important and should be included in future studies in which vasodilatation methods are evaluated.

Necrotic and apoptotic cells serve as nuclei for calcification on osteoblastic differentiation of human mesenchymal stem cells in vitro.

A close relationship between cell death and pathological calcification has recently been reported, such as vascular calcification in atherosclerosis. However, the roles of cell death in calcification by osteoblast lineage have not been elucidated in detail. In this study, we investigated whether cell death is involved in the calcification on osteoblastic differentiation of human bone marrow mesenchymal stem cells (hMSC) under osteogenic culture in vitro. Apoptosis and necrosis occurred in an osteogenic culture of hMSC, and cell death preceded calcification. The generation of intracellular reactive oxygen species, chromatin condensation and fragmentation, and caspase-3 activation increased in this culture. A pan-caspase inhibitor (Z-VAD-FMK) and anti-oxidants (Tiron and n-acetylcysteine) inhibited osteogenic culture-induced cell death and calcification. Furthermore, calcification was significantly promoted by the addition of necrotic dead cells or its membrane fraction. Spontaneously dead cells by osteogenic culture and exogenously added necrotic cells were surrounded by calcium deposits. Induction of localized cell death by photodynamic treatment in the osteogenic culture resulted in co-localized calcification. These findings show that necrotic and apoptotic cell deaths were induced in an osteogenic culture of hMSC and indicated that both necrotic and apoptotic cells of osteoblast lineage served as nuclei for calcification on osteoblastic differentiation of hMSC in vitro.

Mitochondrial localization of ABC transporter ABCG2 and its function in 5-aminolevulinic acid-mediated protoporphyrin IX accumulation.

Accumulation of protoporphyrin IX (PpIX) in malignant cells is the basis of 5-aminolevulinic acid (ALA)-mediated photodynamic therapy. We studied the expression of proteins that possibly affect ALA-mediated PpIX accumulation, namely oligopeptide transporter-1 and -2, ferrochelatase and ATP-binding cassette transporter G2 (ABCG2), in several tumor cell lines. Among these proteins, only ABCG2 correlated negatively with ALA-mediated PpIX accumulation. Both a subcellular fractionation study and confocal laser microscopic analysis revealed that ABCG2 was distributed not only in the plasma membrane but also intracellular organelles, including mitochondria. In addition, mitochondrial ABCG2 regulated the content of ALA-mediated PpIX in mitochondria, and Ko143, a specific inhibitor of ABCG2, enhanced mitochondrial PpIX accumulation. To clarify the possible roles of mitochondrial ABCG2, we characterized stably transfected-HEK (ST-HEK) cells overexpressing ABCG2. In these ST-HEK cells, functionally active ABCG2 was detected in mitochondria, and treatment with Ko143 increased ALA-mediated mitochondrial PpIX accumulation. Moreover, the mitochondria isolated from ST-HEK cells exported doxorubicin probably through ABCG2, because the export of doxorubicin was inhibited by Ko143. The susceptibility of ABCG2 distributed in mitochondria to proteinase K, endoglycosidase H and peptide-N-glycosidase F suggested that ABCG2 in mitochondrial fraction is modified by N-glycans and trafficked through the endoplasmic reticulum and Golgi apparatus and finally localizes within the mitochondria. Thus, it was found that ABCG2 distributed in mitochondria is a functional transporter and that the mitochondrial ABCG2 regulates ALA-mediated PpIX level through PpIX export from mitochondria to the cytosol.

Spred-2 deficiency exacerbates acetaminophen-induced hepatotoxicity in mice.

MAPKs are involved in acetaminophen (APAP)-hepatotoxicity, but the regulatory mechanism remains unknown. Here, we explored the role of Spred-2 that negatively regulates Ras/ERK pathway in APAP-hepatotoxicity. Spred-2 knockout (KO) mice demonstrated exacerbated liver injury, an event that was associated with increased numbers of CD4(+) T, CD8(+) T and NK cells in the liver compared to the control. Levels of CXCL9/CXCL10 that attract and activate these cells were increased in Spred-2 KO-liver. Kupffer cells isolated from Spred-2 KO mice after APAP challenge expressed higher levels of CXCL9/CXCL10 than those from the control. Upon stimulation with APAP or IFNγ, naïve Kupffer cells from Spred-2 KO mice expressed higher levels of CXCL9/CXCL10. NK cell-depletion attenuated APAP-hepatotoxicity with lowered hepatic IFNγ and decreased numbers of not only NK cells but also CD4(+) T and CD8(+) T cells in the liver. These results suggest that Spred-2 negatively regulates APAP-hepatotoxicity under the control of Kupffer cells and NK cells.

Favorable response of heavily treated Wilms' tumor to paclitaxel and carboplatin.

BACKGROUND: Heavily treated Wilms' tumor responding to the combination of paclitaxel and carboplatin has not yet been reported. CASE REPORT: A 17-year-old man presented with hematuria. He received a diagnosis of Wilms' tumor with multiple lung metastases and was treated with preoperative chemotherapy including vincristine, dactinomycin, and doxorubicin, a right nephrectomy, and adjuvant chemotherapy, followed by pulmonary metastasectomy. During the next 8 years, he suffered from 4 relapses and has been treated with multiple anticancer agents including high-dose chemotherapy with autologous peripheral blood stem cell transplantation. Finally, the disease progressed due to peritoneal and pleural metastases. With opioid administration for left shoulder pain due to pleural metastasis, he received combination chemotherapy with carboplatin (area under the curve = 4) and paclitaxel (175 mg/m(2)) on day 1. After 2 cycles, he achieved a partial response with mild toxicity. He received 7 cycles of the chemotherapy and the time to progression was 200 days. CONCLUSION: In a refractory case after intensive treatments, we succeeded to control the disease for a while.