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Helicobacter pylori infection causes gastric cancer, the third leading cause of cancer death worldwide. More than half of the world’s population is infected, making universal eradication impractical. Clinical trials suggest that antibiotic treatment only reduces gastric cancer risk in patients with non-atrophic gastritis (NAG), and is ineffective once preneoplastic lesions of multifocal atrophic gastritis (MAG) and intestinal metaplasia (IM) have occurred. Therefore, additional strategies for risk stratification and chemoprevention of gastric cancer are needed. We have implicated polyamines, generated by the rate-limiting enzyme ornithine decarboxylase (ODC), in gastric carcinogenesis. During H. pylori infection, the enzyme spermine oxidase (SMOX) is induced, which generates hydrogen peroxide from the catabolism of the polyamine spermine. Herein, we assessed the role of SMOX in the increased gastric cancer risk in Colombia associated with the Andean mountain region when compared with the low-risk region on the Pacific coast. When cocultured with gastric epithelial cells, clinical strains of H. pylori from the high-risk region induced more SMOX expression and oxidative DNA damage, and less apoptosis than low-risk strains. These findings were not attributable to differences in the cytotoxin-associated gene A oncoprotein. Gastric tissues from subjects from the high-risk region exhibited greater levels of SMOX and oxidative DNA damage by immunohistochemistry and flow cytometry, and this occurred in NAG, MAG and IM. In Mongolian gerbils, a prototype colonizing strain from the high-risk region induced more SMOX, DNA damage, dysplasia and adenocarcinoma than a colonizing strain from the low-risk region. Treatment of gerbils with either α-difluoromethylornithine, an inhibitor of ODC, or MDL 72527 ( N 1 , N 4 -Di(buta-2,3-dien-1-yl)butane-1,4-diamine dihydrochloride), an inhibitor of SMOX, reduced gastric dysplasia and carcinoma, as well as apoptosis-resistant cells with DNA damage. These data indicate that aberrant activation of polyamine-driven oxidative stress is a marker of gastric cancer risk and a target for chemoprevention.

To establish the timing of lineage restriction among endodermal derivatives, we developed a method to label permanently subsets of lung precursor cells at defined times during development by using Cre recombinase to activate floxed alkaline phosphatase or green fluorescent protein genes under control of doxycycline-dependent surfactant protein C promoter. Extensive or complete labeling of peripheral lung, thyroid, and thymic epithelia, but not trachea, bronchi, or gastrointestinal tract occurred when mice were exposed to doxycycline from embryonic day (E) 4.5 to E6.5. Non-overlapping cell lineages of conducting airways (trachea and bronchi), as distinct from those of peripheral airways (bronchioles, acini, and alveoli), were established well before formation of the definitive lung buds at E9-9.5. At E11.5, the labeled precursors of peripheral lung were restricted to relatively few cells along the bronchial tubes and clusters in bronchial tips and lateral buds. Thereafter, these cells underwent marked expansion to form the entire gas-exchange region in the lung. This study demonstrates early restriction of endodermal progenitor cells forming peripheral as compared with proximal airways, identifies distinct cell lineages in conducting airways, and distinguishes neuroepithelial and tracheal-bronchial gland cell lineages from those lining peripheral regions of the lung. This system for conditional gene addition or deletion is useful for the study of lung morphogenesis and gene function in vivo, and identifies progenitor cells that may serve as useful targets for cell or gene replacement for pulmonary disorders.

Targeted disruption of the histidine decarboxylase gene (HDC-/-), the only histamine-synthesizing enzyme, led to a histamine-deficient mice characterized by undetectable tissue histamine levels, impaired gastric acid secretion, impaired passive cutaneous anaphylaxis, and decreased mast cell degranulation. We used this model to study the role of histamine in bone physiology. Compared with WT mice, HDC-/- mice receiving a histamine-free diet had increased bone mineral density, increased cortical bone thickness, higher rate of bone formation, and a marked decrease in osteoclasts. After ovariectomy, cortical and trabecular bone loss was reduced by 50% in HDC-/- mice compared with WT. Histamine deficiency protected the skeleton from osteoporosis directly, by inhibiting osteoclastogenesis, and indirectly, by increasing calcitriol synthesis. Quantitative RT-PCR showed elevated 25-hydroxyvitamin D-1α-hydroxylase and markedly decreased 25-hydroxyvitamin D-24-hydroxylase mRNA levels. Serum parameters confirming this indirect effect included elevated calcitriol, phosphorus, alkaline phosphatase, and receptor activator of NF-κ B ligand concentrations, and suppressed parathyroid hormone concentrations in HDC-/- mice compared with WT mice. After ovariectomy, histamine-deficient mice were protected from bone loss by the combination of increased bone formation and reduced bone resorption.

In mammals, dosage compensation of X-linked genes is achieved by the transcriptional silencing of one X chromosome in the female (reviewed in ref. 1 ). This process, called X inactivation, is usually random in the embryo proper. In marsupials and the extra-embryonic region of the mouse, however, X inactivation is imprinted: the paternal X chromosome is preferentially inactivated whereas the maternal X is always active. Having more than one active X chromosome is deleterious to extra-embryonic development in the mouse 2 . Here we show that the gene eed (embryonic ectoderm development) 3 , 4 , a member of the mouse Polycomb group ( Pc-G ) of genes, is required for primary and secondary trophoblast giant cell development in female embryos. Results from mice carrying a paternally inherited X-linked green fluorescent protein (GFP) transgene implicate eed in the stable maintenance of imprinted X inactivation in extra-embryonic tissues. Based on the recent finding that the Eed protein interacts with histone deacetylases, we suggest that this maintenance activity involves hypoacetylation of the inactivated paternal X chromosome in the extra-embryonic tissues.

Owing to their extremely high specific surfaces and their high surface-to-volume ratios nanosized ceramic powders show a strong tendency to agglomeration and poor flowability. For improved properties of these powders during storage, transport and shaping a granulation step is necessary. However, the granules must be completely destroyed during dry pressing or redispersion; otherwise, the advantages of nanoparticles in comparison to conventional powders will not be realized. Spray freezing is a new granulation technique which combines the advantages of a conventional granulation by spray drying and a sublimation drying process. Different suspensions of nanosized oxide powders were rapidly frozen by spray freezing and subsequently dried by freeze drying. Thus, capillary forces can be excluded by this process. The achieved granulates show spheric granules with very low strength, improved flowability and increased bulk density. They were redispersible and can be destroyed under very low pressures.[PUBLICATION ABSTRACT]

Stem cells have generated considerable interest recently in the scientific, clinical, and public arenas. The third book in the Stem Cell Repair and Regeneration series offers contributions from numerous areas bridging medicine and the life sciences.Significant research activities in the tissue engineering or regenerative medicine (the term recently used) field started in the 1970s, and there is currently great excitement over the possibility of replacing damaged body parts through regenerative medicine. Potential strategies to replace, repair and restore the function of damaged tissues or organs include stem cell transplantation, transplantation of tissues engineered in the laboratory, and the induction of regeneration by the body's own cells. It is believed that novel cellular therapeutics outperform any medical device, recombinant protein or chemical compound.This volume explores novel stem cell therapeutic strategies for myriad diseases, including renal failure, retinal disease and myocardial infarction.Sample Chapter(s)Chapter 1: The Biology of Human Mesenchymal Stem Cells (96 KB)Contents:The Biology of Human Mesenchymal Stem Cells (C Westwood M O Clements)Mesenchymal Stem Cells: From Culture to Clinic (C A Gregory)Stem Cell Bioprocessing for Clinical Applications of Regenerative Medicine (A Mantalaris et al.)Defining and Overcoming the Immunological Barriers to Stem Cell Therapies (N J Robertson et al.)Activation of the Immune System: A Corollary of Transplantation with ES Cell-Derived Tissues (A S Boyd et al.)Suppression of HLA Expression by Lentivirus-Mediated Gene Transfer of siRNA Cassettes (N Kasahara)Cord Blood Cells for Myocardial Regeneration (C Stamm M Nan)Clinical Trials in Cardiac Stem Cell Therapy: An Update (R Kam I Dimarakis)Stem Cell Therapy in Neurodegenerative Disease (C T Flores M Y Gordon)Adult Human Stem Cell Therapy for Ischemic Stroke (D Williamson et al.)Cell Therapy in Renal Disease (H D Humes)Regenerative Medicine of the Eye: A Short Review (D T Harris et al.)A Clearer View of Stem Cells in Retinal Disease (M D Hodges et al.)Limbal Epithelial Stem Cells: Biology and Therapeutic Potential (M Notara et al.)The Use of Mesenchymal Stem Cells for Bone and Cartilage Repair (R Behan et al.)Readership: Life science scientists; biomedical researchers; academics, postgraduate students and advanced undergraduate students in cell biology, biochemistry and genetics; surgeons; clinicians; biotechnology and pharmaceutical industry professionals.

Light-curve modeling of the W UMa class of binary-star systems is now done by a number of authors. A solution of the photoelectric R and I observations of AK Her by Bookmyer and Kaitchuck (1979) are presented and compared to four different analyses of three different sets of photoelectric B and V observations. The set of parameters solved for in each case varies as do the limits of the numerical values of some of the parameters, most notably the reflection albedo. The results do differ but even though the methods are divergent, the results are fairly consistent.

An efficient, highly automatic method for the computation of synthetic light curves has been developed expressly for the W UMa class of binary stars for which proximity effects are important. An intercomparison of the computer programs currently in use is given. The present method has been found to be a factor of three faster than the method of Wilson and Devinney. The results of this computer model as applied to two sets of observations of the A-type, binary system V566 Oph (Bookmyer 1969, 1976) are presented.

Lymphangiomas are rare benign lymphatic tumours found predominantly in the head and neck region. A case of a cavernous lymphangioma isolated to the sphenoid sinus is described. The authors emphasize the extreme rarity of the isolated sphenoid lymphangioma, as to their knowledge this is the first report in the English literature.

Polar bears (Ursus maritimus) of the southern Beaufort Sea population, distributed from approximately Icy Cape, west of Point Barrow, Alaska, to Pearce Point, east of Paulatuk in Canada, are harvested by hunters from both countries. In Canada, quotas to control polar bear hunting have been in place, with periodic modifications, since 1968. In Alaska, passage of the United States Marine Mammal Protection Act (MMPA) of 1972 banned polar bear hunting unless done by Alaska Natives for subsistence. However, the MMPA placed no restrictions on numbers or composition of the subsistence hunt, leaving open the potential for an overharvest with no possible legal management response until the population was declared depleted. Recognizing that as a threat to the conservation of the shared polar bear population, the Inuvialuit Game Council from Canada and the North Slope Borough from Alaska negotiated and signed a user-to-user agreement, the Polar Bear Management Agreement for the Southern Beaufort Sea, in 1988. We reviewed the functioning of the agreement through its first 10 years and concluded that, overall, it has been successful because both the total harvest and the proportion of females in the harvest have been contained within sustainable limits. However, harvest monitoring needs to be improved in Alaska, and awareness of the need to prevent overharvest of females needs to be increased in both countries. This agreement is a useful model for other user-to-user conservation agreements. /// Les ours polaires (Ursus maritimus) constituant la population de la mer de Beaufort méridionale sont répartis d'environ Icy Cape, à l'ouest de Point Barrow (Alaska), à Pearce Point, à l'est de Paulatuk (Canada). Ils sont prélevés par des chasseurs des deux pays. Au Canada, les quotas visant le contrôle de la chasse à l'ours polaire sont en vigueur - avec des modifications périodiques - depuis 1968. En Alaska, l'adoption en 1972 de la loi américaine (MMPA) visant la protection des mammifères marins a interdit la chasse à l'ours polaire sauf la chasse de subsistance pratiquée par les Autochtones alaskiens. La MMPA n'a toutefois placé aucune restriction sur le nombre ou la composition de la chasse de subsistance, laissant la porte ouverte à une éventuelle surexploitation sans possibilité d'une réaction de gestion sur le plan légal jusqu'à ce que la population soit déclarée décimée. Reconnaissant en cela une menace à la conservation de la population commune d'ours polaires, le Conseil canadien de gestion du gibier et le North Slope Borough de l'Alaska ont négocié et signé en 1988 une entente entre usagers, le Polar Bear Management Agreement pour la mer de Beaufort méridionale. On a examiné le fonctionnement de l'entente durant sa première décennie pour conclure que, dans l'ensemble, elle a porté fruit car le total des prises et la proportion de femelles prélevées ont été maintenus dans des limites viables. Il faut toutefois améliorer le contrôle du prélèvement en Alaska et accroître dans les deux pays la sensibilisation à la nécessité de prévenir une surexploitation des femelles. Cette entente constitue un modèle pour d'autres accords entre usagers en matière de conservation.