Highly efficient ex vivo expansion of human hematopoietic stem cells using Delta1-Fc chimeric protein

Ex vivo expansion of hematopoietic stem cells (HSCs) has been explored in the fields of stem cell biology, gene therapy, and clinical transplantation. Here, we demonstrate efficient ex vivo expansion of HSCs measured by long-term severe combined immunodeficient (SCID) repopulating cells (SRCs) from human cord blood CD133-sorted cells using a soluble form of Delta1. After a 3-week culture on immobilized Delta1 supplemented with stem cell factor, thrombopoietin, Flt-3 ligand, interleukin (IL)-3, and IL-6/soluble IL-6 receptor chimeric protein (FP6) in a serum- and stromal cell-free condition, we achieved approximately sixfold expansion of SRCs when evaluated by limiting dilution/transplantation assays. The maintenance of full multipotency and self-renewal capacity during culture was confirmed by transplantation to nonobese diabetic/SCID/gammac(null) mice, which showed myeloid, B, T, and natural killer cells as well as CD133(+)CD34(+) cells, and hematopoietic reconstitution in the secondary recipients. Interestingly, the CD133-sorted cells contained approximately 4.5 times more SRCs than the CD34-sorted cells. The present study provides a promising method to expand HSCs and encourages future trials on clinical transplantation.     

Detection of contractions in adaptive transit time of the small bowel from wireless capsule endoscopy videos

Recognizing intestinal contractions from wireless capsule endoscopy (WCE) image sequences provides a non-invasive method of measurement, and suggests a solution to the problems of traditional techniques for assessing intestinal motility. Based on the characteristics of contractile patterns and information on their frequencies, the contractions can be investigated using essential image features extracted from WCE videos. In this study, we proposed a coherent three-stage procedure using temporal and spatial features. The possible contractions are recognized by changes in the edge structure of the intestinal folds in Stage 1 and evaluating similarity features in consecutive frames in Stage 2. In order to take account of the properties of contraction frequency, we consider that the possible contractions are located within windows including consecutive frames. The size of these contraction windows is adjusted according to the passage of the WCE. These procedures aim to exclude as many non-contractions as possible. True contractions are determined through spatial analysis of directional information in Stage 3. Using the proposed method, 81% of true contractions are detected with a 37% false alarm rate for evaluations in the experiments. The overall performance of this method is better than that of previous methods, in terms of both the quality and quantity indices. The results suggest feasible data for further clinical applications.     

Activin A increases the bone mass of grafted bone in C3H/HeJ mice

Activin A, a member of the TGF-b superfamily, is abundant in bone matrix, but little is known about its physiological role in bone metabolism. The present study was undertaken to determine whether topical activin A can increase the bone mass of isografted bone. The tibiae were bilaterally dissected from a donor C3H/HeJ mouse and transplanted subcutaneously in the dorsal region of a recipient mouse. One isografted tibia was topically infused for either 1, 2, 3, or 4 weeks with activin A, using an osmotic minipump at a dose of 0.02, 0.2, or 2 ng/hr. The other tibia was infused with 0.9% NaCl (control). The following results were obtained: (1) Topical activin A (2 ng/hr) stimulated periosteal bone formation after 2 or 3 weeks. The bone area in a standardized transverse section averaged 1.3 fold that in the control. (2) Numerous cuboidal or conical osteoblasts appeared on the surface of newly formed bone after the infusion of activin A for 2 or 3 weeks. Autoradiographic studies using 3H-proline revealed that the surface area of newly formed bone labelled with autoradiographic silver grains was greater in activin A-treated bone than in the control, suggesting an increased synthesis and secretion of collagen by osteoblasts. (3) Topical activin A increased the number of osteoclasts after 2 to 4 weeks. Furthermore, enhanced or increased bone resorption was observed in the projected anterior site of activin A-treated bone after 4 weeks. These results suggest that topical activin A increases the bone mass of isografted bone by increasing bone turnover.     

Studies on the polymerization of vinyl compounds in the presence of metal salts, 9. On the initiation mechanism of polymerization of acrylamide by ceric salt

In order to elucidate the initiation mechanism of the polymerization of acrylamide by ceric salt, the complexation of ceric salt with acrylamide and its methylated derivatives was investigated by IR and NMR spectrometry. The decomposition of the complex was also studied by determining the rate of ceric salt consumption. From the results it was concluded that the oxygen of acrylamide coordinates with the ceric ion to form the complex and that a radical is produced by abstraction of a hydrogen atom from the amide group of the molecule to initiate the polymerization.     

Clinical efficacy of 5-fluorouracil (5-FU) topical cream for treatment of cholesteatoma

OBJECTIVE: In order to clarify clinical efficacy of commercially available 5-fluorouracil (5-FU) topical cream, a clinical study was conducted. METHODS: Two to three cubic millimetres of 5-FU topical cream (Kyowa, Roche) was applied on 50 cases of various types of cholesteatoma (50 patients) two to five times with the interval of 2 weeks, and its clinical efficacy was evaluated by the criteria we developed. RESULTS: In total, 59% of the cholesteatomas showed good effect, 29% of them showed fair effect, and the effect was poor in the remaining 12%. It was particularly effective in cholesteatomas in the EAC, attic cholesteatomas with an aerated mastoid, and in recurrent-type cholesteatomas. CONCLUSION: 5-FU topical cream appeared effective for the treatment of cholesteatomas.     

Projections to the alimentary canal from the dopaminergic neurons in the dorsal motor nucleus of the vagus of the rat

The motility of the alimentary canal is regulated not only by neurons that contain acetylcholine or adrenaline, but also by nonadrenergic noncholinergic neurons. There are many neurons containing dopamine in the dorsal motor nucleus of the vagus (DMV). We examined the projections of these dopaminergic neurons to the alimentary canal with double-labeling immunohistochemistry for tyrosine hydroxylase (TH) and the retrograde tracer cholera toxin subunit b following its injection into the subdiaphragmatic esophagus, the cardia, the pylorus, the duodenum, the jejunum, and the ascending colon. Almost all double-labeled neurons were found in the half of the DMV caudal to the area postrema. In the caudal half of the DMV, about 58% of the TH-immunoreactive neurons projected to the cardia, about 36% projected to the pylorus, and about 28% projected to the subdiaphragmatic esophagus. Only a few TH-immunoreactive neurons projected to the duodenum, the jejunum, or the ascending colon. As a whole, less than 10% of the neurons in the DMV that projected to the alimentary canal showed TH-like immunoreactivity. These results suggest that some of the dopaminergic neurons in the DMV might regulate the activities of the stomach and the subdiaphragmatic esophagus.     

Chronic lithium treatment decreases tau lesions by promoting ubiquitination in a mouse model of tauopathies

Lithium, a widely used drug for treating affective disorders, is known to inhibit glycogen synthase kinase-3 (GSK-3), which is one of the major tau kinases. Thus, lithium could have therapeutic benefit in neurodegenerative tauopathies by reducing tau hyperphosphorylation. We tested this hypothesis and showed that long-term administration of lithium at relatively low therapeutic concentrations to transgenic mice that recapitulate Alzheimers disease (AD)-like tau pathologies reduces tau lesions, primarily by promoting their ubiquitination rather than by inhibiting tau phosphorylation. These findings suggest novel mechanisms whereby lithium treatment could ameliorate tauopathies including AD. Because lithium also has been shown to reduce the burden of amyloid- pathologies, it is plausible that lithium could reduce the formation of both amyloid plaques and tau tangles, the two pathological hallmarks of AD, and thereby ameliorate the behavioral deficits in AD.     

T staging of gastric cancer: role of multi-detector row CT

PURPOSE: To evaluate retrospectively the accuracy of multi-detector row computed tomography (CT) in the assessment of serosal invasion in patients with gastric cancer. MATERIALS AND METHODS: The Ethics Committee does not require approval or informed consent for retrospective studies. Forty-one consecutive patients (24 men, 17 women; mean age, 68 years) with gastric cancer were included in this study. All patients were given 600 mL of tap water to drink and were positioned prone or supine on the scanning table. The detector row configuration included four detector rows, a section thickness of 1.25 mm, a pitch of 6, and a reconstruction interval of 0.63 mm. Transverse and multiplanar reconstruction images were simultaneously evaluated by two independent observers to assess the depth of tumor invasion in the gastric wall (ie, T stage). T staging at multi-detector row CT was compared with T staging at histologic evaluation (reference standard), which was performed by means of surgical or histologic examination of the resected specimen. We also calculated the sensitivity, specificity, and accuracy of multi-detector row CT for each observer in the assessment of serosal invasion. RESULTS: Analysis of interobserver agreement showed substantial or almost perfect agreement (nonweighted kappa value of 0.78 and weighted kappa value of 0.85). Correct assessment of gastric wall invasion was 80% and 85% for observers 1 and 2, respectively. The sensitivity, specificity, and accuracy of multi-detector row CT in the assessment of serosal invasion were 90%, 95%, and 93%, respectively, for observer 1 and 80%, 97%, and 93%, respectively, for observer 2. Overstaging occurred in six patients, and understaging occurred in five patients. All understaged tumors were scirrhous subtype gastric cancer. CONCLUSION: Multi-detector row CT scanning of patients with gastric cancer gave 93% accuracy in the assessment of serosal invasion in patients with gastric cancer.