Climbing exercise enhances osteoblast differentiation and inhibits adipogenic differentiation with high expression of PTH/PTHrP receptor in bone marrow cells

We developed previously a mouse voluntary climbing exercise model as a physiological mechanical loading model and reported that climbing exercise increased bone formation, but its effect on adipogenesis is unknown. We assessed the effects of loading and PTH/PTHrP receptor (PTHR1) on bone marrow adipocyte differentiation in relation with osteoblast differentiation. 8-week-old C57BL/6J male mice were divided into ground control (GC) and climbing exercise (EX) group. Mice were housed in 100-cm towers and climbed up toward a bottle placed at the top of the cage to drink water. The values of bone volume and osteoblast number were significantly higher while those of marrow adipocyte volume and number were significantly lower in the 28dayEX group than 28dayGC group. The mRNA expression levels of adipocyte differentiation genes CCAAT/enhancer-binding proteins (C/EBP) beta and delta were lower in 4dayEX mice, while the adipocyte specific genes fatty acid binding protein (aP2) and phosphoenolpyruvate carboxykinase (PEPCK) expressions were lower in 7dayEX mice. In primary bone marrow cell cultures, the number of alkaline phosphatase-positive colony forming units-fibroblastic (ALP+ CFU-f) and Oil-red-O-positive cells were both increased in the 4dayEX group. Climbing exercise transiently increases both osteogenic and adipogenic potential in bone marrow stromal cells, and inhibits terminal adipocyte differentiation and promotes osteoblast differentiation. Immunoreactivity for the PTHR1 was intense on osteoblastic cell lineage in the endosteal tibial metaphysis. PTHR1 mRNA expression was increased in 4dayEX mice and PTHR1-positive cells were increased after 7 days in the experimental group. Ex vivo addition of PTHR1 antibody decreased and that of PTHrP(1-34) increased the number of ALP+ CFU-f in bone marrow cell cultures obtained at 4 days after the exercise, while the addition of PTHR1 antibody increased and PTHrP(1-34) decreased the number of Oil-red-O-positive cells. Our results indicate that climbing exercise enhanced osteoblast differentiation and inhibited terminal differentiation of adipocyte progenitors with high expression of PTHR1 in bone marrow cells.     

Prevalence of Synchronous Colorectal Neoplasms Detected by Colonoscopy in Patients with Gastric Cancer

Purpose Our purpose was to study the characteristics of colorectal neoplasms in patients with gastric cancer (GC). Methods The study group comprised GC patients who underwent colonoscopy before resection of their GC. We examined the prevalence, site, and histology of colorectal neoplasms, as well as the clinicopathological features and treatment of the patients who had synchronous colorectal cancers (CRC). The logistic regression model was applied to investigate the features of the GC patients with concurrent CRC. Results We studied 466 GC patients (mean age 64.5 years; 147 women, 319 men), 143 (31%) of whom had a family history of gastrointestinal cancer. Synchronous colorectal adenoma and cancer were detected in 182 (39%) and 18 (4%) patients, respectively. Among the 18 synchronous CRCs, 11 were in the early stages and 10 of these were resected endoscopically. The other eight required simultaneous open radical surgery. All the GC patients with synchronous CRC were older than 50 years. Statistical analysis did not show a significant difference between the features of the patients with and those without concurrent CRC. Conclusions The possibility of synchronous colorectal neoplasms in GC patients cannot be disregarded in clinical practice; however, screening of the large bowel may not be necessary in GC patients younger than 50 years.     

Biliary complications in right lateral sector graft live donor liver transplantation.

Biliary complications remain the most challenging issue in adult living donor liver transplantation (LDLT) and to the best of our knowledge, no study has focused on the biliary complications in LDLT with right lateral sector graft (RLSG), a graft consisting of segments VI and VII according to Couinaud's nomenclature for liver segmentation. Between January 1996 and October 2006, 310 LDLTs were performed for adult recipients at our institution. Among them, 20 patients received RLSG. The incidence of biliary complications during follow-up in these patients with RLSG was retrospectively analyzed. Follow-up period after transplantation ranged from 1 to 87 months (median 58 months). The 3-year and 5-year graft survival rates following the use of RLSGs in LDLT were 90% and 90%, respectively. Biliary complications were encountered in altogether nine patients. Two patients (10%) were complicated with bile leakage requiring surgical intervention. Seven patients (35%) were complicated with bile duct stenosis, which occurred with a median interval of 26 months (range: 6-51 months) after LDLT. Four were treated surgically and the other three were treated by endoscopic approach. Outcomes of the interventions were satisfactory in all cases. The incidence and severity of biliary complications after LDLT using RLSG was within an acceptable range with excellent graft survival. Accordingly, it is concluded that RLSG is a technically feasible option that may effectively expand the donor pool. Further application of RLSG is warranted.     

Pre-emptive renal transplantation in children

BACKGROUND: Renal transplantation is a definitive therapeutic modality in end-stage renal disease (ESRD). Most ESRD patients in Japan experience dialysis prior to renal transplantation. The present study was undertaken to examine the usefulness of pre-emptive renal transplantation (PET). METHODS: Between 1987 and 1998, 255 renal transplantations were carried out by the authors. Among those consecutive cases, 10 were cases of PET. In nine pediatric cases, demographics, graft and patient survival, height growth and benefits from successful transplantation were studied and compared with age-matched dialyzed transplantation controls. RESULTS: All transplantation was living-related. There was a disparity of causes of ESRD between the two groups. In PET, acquired renal deterioration due to a congenital lower urinary tract disorder was the major cause. Graft and patient prognosis was favorable in both groups. Growth retardation in PET patients under 15 years of age was significantly less apparent at the time of transplantation and after 3 years compared to the control. The benefits from transplantation were different in the two groups. Most PET patients felt an improvement of their physical condition; however, all of the control patients felt that the major boon was the freedom from the restriction of the daily diet and time for dialysis. CONCLUSION: In pediatric renal transplantation, short-term preceding dialysis does not have a detrimental effect, but PET could benefit ESRD patients by maintaining their quality of life. Moreover, PET minimizes the production of renal dwarfism in prepubertal children. Thus, PET should be taken into consideration in the choice of renal replacement therapy.     

Simultaneous hepatic artery and portal vein thrombosis after living donor liver transplantation

Simultaneous hepatic artery and portal vein thrombosis rarely occurs after liver transplantation. The etiology is unknown. Of 213 patients (72 children and 141 adults) that underwent living donor liver transplantation (LDLT) from January 1996 to March 2003, 4 (2%) developed simultaneous thrombosis at 3 hours to 7 days (median, 4 days) after the operation. Emergent thrombectomy was performed in three patients; the remaining patient was registered in the Japan organ transplant network. All of the patients died due to hepatic failure (range, 18 hours to 6 days after the diagnosis; median, 2 days). Portal vein, hepatic artery, and hepatic vein velocity in the liver graft were measured every 12 hours by Doppler ultrasonography for 2 weeks after liver transplantation. These parameters were stable until just before the simultaneous thrombosis. These findings indicate that protocol Doppler ultrasonography can diagnose, but not predict, this fatal complication.     

Micro-segmental hair analysis: detailed procedures and applications in forensic toxicology

Forensic Toxicology - Since the 1980s, the detection sensitivity of mass spectrometers has increased by improving the analysis of drugs in hair. Accordingly, the number of hair strands required for...     

Thin-layer chromatography on silver nitrate-impregnated silica gel for analysis of homemade tetrahydrocannabinol mixtures

Forensic Toxicology - Various forms of cannabidiol (CBD)-containing products are sold in Japan. CBD is easily converted to mixtures of ?9-tetrahydrocannabinol (?9-THC) and its isomer,...     

A screening model for low bone mass in elderly Japanese men using quantitative ultrasound measurements: Fujiwara-Kyo Study

Screening for low bone mass is important to prevent fragility fractures in men as well as women, although men show a much lower prevalence of osteoporosis than women. The purpose of this study was to establish a screening model for low bone mineral density (BMD) using a quantitative ultrasound parameter and easily obtained objective indices for elderly Japanese men. We examined 1633 men (65-84 yr old) who were subjects of the Fujiwara-Kyo Study. Speed of sound (SOS) at the calcaneus was determined, and BMD was measured by dual-energy X-ray absorptiometry at the lumbar spine (LS), total hip (TH), and femoral neck (FN). Low BMD was defined as >1 standard deviation below the young adult mean, in accordance with World Health Organization criteria. We performed receiver operating characteristic (ROC) analysis to identify a better screening model incorporating SOS and determined the optimal cutoff value using Youden index. Prevalences of low BMD at the 3 skeletal sites were 27.8% (LS), 33.5% (TH), 48.6% (FN), and 43.3% at either LS or TH. The greatest area under the ROC curve (0.806, 95% confidence interval: 0.785-0.828) and smallest Akaike's information criterion were obtained in the multivariate model incorporating SOS, age, height, and weight for predicting low BMD at all skeletal sites. This model predicted low BMD at TH with the sensitivity of 0.726 and specificity of 0.739, whereas a similar model predicted low BMD at LS with much lower validity. We conclude that the multivariate model for TH could be used to screen for low BMD in elderly Japanese men.     

Glycolysis inhibitors as a potential therapeutic option to treat aggressive neuroblastoma expressing GLUT1

Background/PurposeIncreased glycolysis is among the biochemical characteristics of cancerous tissue. The glucose transporter isoform 1 (GLUT1) gene encodes a key factor for glucose transport into cancerous tissue. However, the expression and functional significance of GLUT1 in neuroblastoma have not been fully characterized. Therefore, we investigated the association of GLUT1 expression with clinical outcomes in patients with neuroblastoma using immunohistochemical staining for GLUT1 in neuroblastoma tissues. We also assessed the efficacy of glycolysis inhibition as an anticancer treatment in neuroblastoma cell lines with altered expression of GLUT1.MethodsWe obtained total RNA from cancerous tissue by microdissection in 47 patients with neuroblastoma. GLUT1 expression levels were evaluated by quantitative real-time polymerase chain reaction. We analyzed the association of GLUT1 expression levels with clinical outcomes. We also examined changes in GLUT1 expression and proliferative responses in vitro using 4 neuroblastoma cell lines treated with a glycolysis inhibitor, 3-Bromopyruvate acid.ResultsElevated GLUT1 expression was associated with poor prognosis. Moreover, elevated GLUT1 expression independently predicted overall survival. Immunohistochemical analysis showed that GLUT1 expression tended to be localized to the centers of neuroblastoma cell nests. Our in vitro studies showed that 3-Bromopyruvate acid significantly suppressed the proliferation of neuroblastoma cells with high GLUT1 gene expression compared with those with low expression.ConclusionGlycolysis inhibitors are a potential therapeutic option for treating aggressive tumors expressing GLUT1.