Molecular characterization of the recurrent unbalanced translocation der(1;7)(q10;p10)

An unbalanced translocation der(1;7)(q10; p10) is a nonrandom chromosomal aberration commonly observed in myelodysplastic syndrome and acute myeloid leukemia. We molecularly analyzed the breakpoints of der(1;7)(q10;p10) by quantitative fluorescent in situ hybridization (FISH) analyses using centromeric satellite DNAs mapped to chromosomes 1 and 7 as probes. We found that the signal intensities of 2 centromere alphoid probes, D1Z7 on chromosome 1 and D7Z1 on chromosome 7, were almost invariably reduced on the derivative chromosome compared with those on their normal counterparts. These results suggest that this translocation results from the recombination between the 2 alphoids, which was further confirmed by fiber FISH experiments. Because the relative reduction in the intensities of D1Z7 and D7Z1 signals on the derivative chromosomes was highly variable among patients, it was estimated that the breakpoints in these patients were randomly distributed over several megabase pairs within each alphoid cluster except for its extreme end to the short arm. Our results provide a novel insight into the structural basis for generation of this translocation as well as its leukemogenic roles.     

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.