ESCs are a potential cell source for cell therapy. However, there is no evidence that cell transplantation using ESCderived hepatocytes is therapeutically effective. The main objective of this study was to assess the therapeutic efficacy of the transplantation of ESC-derived endodermal cells into a liver injury model. The ␤-galactosidase-labeled mouse ESCs were differentiated into ␣-fetoprotein (AFP)-producing endodermal cells. AFP-producing cells or ESCs were transplanted into transgenic mice that expressed diphtheria toxin (DT) receptors under the control of an albumin enhancer/promoter. Selective damage was induced in the recipient hepatocytes by the administration of DT. Although the transplanted AFP-producing cells had repopulated only 3.4% of the total liver mass 7 days after cell transplantation, they replaced 32.8% of the liver by day 35. However, these engrafted cells decreased (18.3% at day 40 and 7.9% at day 50) after the cessation of DT administration, and few donor cells were observed by days 60 -90. The survival rate of the AFP-producing cell-transplanted group (66.7%) was significantly higher in comparison with that of the sham-operated group (17.6%). No tumors were detected by day 50 in the AFP-producing cell-transplanted group; however, splenic teratomas did form 60 days or more after transplantation. ESC transplantation had no effect on survival rates; furthermore, there was a high frequency of tumors in the ESC-transplanted group 35 days after transplantation. In conclusion, this study demonstrates, for the first time, that ESC-derived endodermal cells improve the survival rates after transplantation into mice with induced hepatocellular injury. STEM CELLS 2007;25:3252-3260 Disclosure of potential conflicts of interest is found at the end of this article.

The transplanted cells were engrafted and repopulated the liver of recipient mice, resulting in the improvement of the survival rate of the liver injury model mice. We therefore propose that HPCs are a desirable cell source for cell transplantation.

This study aimed to determine the characteristics of the Helicobacter pylori host NY43 strain and its prophage-cured derivative. H. pylori colonizing the human stomach cause many diseases. They show high genetic diversity, allowing the development of mutant strains that can form bacterial communities adapted to specific environmental conditions. Bacteriophage activities are associated with bacterial evolution, including pathogenicity development. Herein, we reported the complete genome sequence and genomic organization of two H. pylori prophages, KHP30 and KHP40; the effects of KHP30 on the behaviours of NY43 are not yet known. We showed that approximately 57 % prophage-cured derivatives spontaneously appeared in the exponential phase during liquid culture, and the biological characteristics of these derivatives differed from those of the host NY43. KHP30 reinfected the cured derivatives, and the curing ratio was influenced by culture conditions. KHP30 was shown to promote the development of a flexible H. pylori community with variable characteristics.

A ccidental hypothermia is a serious condition, often with fatal consequences. 1-3 Several active internal rewarming modalities have been described in its management. 4 However, currently, there is no worldwide consensus concerning severity staging and rewarming strategy according to the severity of hypothermia. 2 We report here a case of accidental hypothermia in which continuous venovenous hemodiafiltration (CVVHDF) in combination with a convective air warmer was successfully used as a rewarming technique. We present it with a review of the literature. CASE REPORTA 48-year-old Japanese man was admitted in coma, with severe hemodynamic derangement, bradypnea (SpO 2 85%), anemia (Hb 11.2 g/dL), a marked metabolic acidosis composed of lactic acidosis (pH 7.186, BE -17.8 mmol/L, Lac 121 mg/dL), and severe accidental hypothermia secondary to environmental cold exposure because of consciousness loss after his suicide attempt by cutting the surface skin of both the neck and extremities. On admission, initial examination showed a Glasgow Coma Scale score of 6 and a rectal temperature (core body temperature) of 26.4°C. Twelve-lead electrocardiography (ECG) showed J (Osborn) waves 5 and a prolonged QT interval (Fig. 1).There was no mandatory indication for rewarming by cardiopulmonary bypass because stable circulatory conditions existed. The patient was resuscitated initially with warm intravenous fluids containing dopamine in combination with a convective air warmer. However, this method was slow and the clinical condition was not improved. Therefore, we decided to add a rewarming technique of extracorporeal circulation, continuous venovenous hemodiafiltration (CVVHDF), through cannulation of the femoral vein. The heat transfer was mainly from dialysate warming unit. This dialysate warming unit was well controllable in the fluid temperature in circuit. Moreover, we managed to prevent heat loss from the extracorporeal tubing as follows: we kept the room temperature high and shortened the length of a tube of circuit, and regulated the temperature setting of dialysate warming unit according to body temperature.Consequently, this combination of treatments brought his temperature from 26.8°C to 33.0°C during a 4.5-hour dialysis, with an average rise of 1.37°C/hour (range: 0.2-2.0°C/ hour). His body temperature reached 36.1°C 7.5 hours later, and the J waves on ECG disappeared. The metabolic acidosis was improved (pH 7.354, BE Ϫ3.2 mmol/L, Lac 6.3 mg/dL) 4.0 hours later. Although rhabdomyolysis (CPK 5929 u/L) developed, we did not apparently recognize both the changing of serum potassium and acute myoglobinuric renal failure. The circulatory dynamics was constantly stable in the phase of CVVHDF at a bypass flow rate of 80 to 82 mL/min.The clinical situation clearly improved during the hemodiafiltration session and the patient recovered consciousness after 2.5 hours, with no neurologic sequelae. His medical condition gradually improved without major complications. He was discharged from the emergency and critical care ward on ...

BackgroundRegorafenib is an oral multikinase inhibitor that has been demonstrated as clinically effective in patients with metastatic colorectal cancer in phase III studies. Although disease control was achieved in 40% of the pretreated patients with metastatic colorectal cancer in the pivotal studies, radiological response has rarely been reported. Severe adverse events associated with regorafenib are known to occur during the first and second courses of treatment. We present a case of a 62-year-old Japanese patient whose metastatic colorectal cancer has been responding to treatment with regorafenib for 2 years.Case presentationA 54-year-old Japanese man visited our institute exhibiting general malaise, and he was diagnosed with ascending colon cancer in April 2006. He underwent right hemicolectomy, and the final staging was T3N0M0, stage II. After 19 months, pulmonary metastasis and anastomotic recurrences were detected, and a series of operations were performed to resect both metastatic lesions. After that, liver metastasis, a duodenal metastasis with right renal invasion, right adrenal metastasis, and para-aortic lymph node metastases were observed during follow-up, and chemotherapy and resection were performed. The patient had metastatic para-aortic lymph nodes after the fifth tumor resection and underwent multiple lines of chemotherapy in April 2014. Regorafenib monotherapy was started at 80 mg/day. Then, regorafenib was increased to 120 mg/day in the second cycle. Regorafenib monotherapy led to 60% tumor shrinkage within the initial 2 months, and the tumor further decreased in size over 4 months until it became unrecognizable on imaging studies. The clinical effects of regorafenib monotherapy have shown a partial response according to Response Evaluation Criteria in Solid Tumors criteria. No severe adverse events were observed, except for mild fatigue and hand-foot syndrome. The patient has received 24 courses of regorafenib over 2 years without exhibiting tumor progression.ConclusionsTo the best of our knowledge, this is the longest treatment with regorafenib without tumor progression ever reported. A reduced dosage of regorafenib at induction may ameliorate the cutaneous and hepatic toxicity associated with its use.