Extracellular matrix survival signals transduced by focal adhesion kinase suppress p53-mediated apoptosis

In many malignant cells, both the anchorage requirement for survival and the function of the p53 tumor suppressor gene are subverted. These effects are consistent with the hypothesis that survival signals from extracellular matrix (ECM) suppress a p53-regulated cell death pathway. We report that survival signals from fibronectin are transduced by the focal adhesion kinase (FAK). If FAK or the correct ECM is absent, cells enter apoptosis through a p53-dependent pathway activated by protein kinase C lambda/iota and cytosolic phospholipase A2. This pathway is suppressible by dominant-negative p53 and Bcl2 but not CrmA. Upon inactivation of p53, cells survive even if they lack matrix signals or FAK. This is the first report that p53 monitors survival signals from ECM/FAK in anchorage- dependent cells.     

Multicast support for mobile hosts using Mobile IP: Design issues and proposed architecture

In this paper, we consider the problem of providing multicast to mobile hosts using Mobile IP for network routing support. Providing multicast in an internetwork with mobile hosts is made difficult because many multicast protocols are inefficient when faced with frequent membership or location changes. This basic difficulty can be handled in a number of ways, but three main problems emerge with most solutions. The tunnel convergence problem, the duplication problem, and the scoping problem are identified in this paper and a set of solutions are proposed. The paper describes an architecture to support IP multicast for mobile hosts using Mobile IP. The basic unicast routing capability of Mobile IP is used to serve as the foundation for the design of a multicast service facility for mobile hosts. We believe that our scheme is transparent to higher layers, simple, flexible, robust, scalable, and, to the extent possible, independent of the underlying multicast routing facility. For example, our scheme could interoperate with DVMRP, MOSPF, CBT, or PIM in the current Internet. Where differences exist between the current version of IP (IPv4) and the next generation protocol (IPv6), these differences and any further optimizations are discussed. This revised version was published online in June 2006 with corrections to the Cover Date.     

Serological survey of antibody to Neospora caninum in Japanese dogs

Prevalence of antibody to Neospora caninum (NC) in Japanese dogs were examined. The antibody was positive in 15 of 48 dogs (31.3%) reared in the dairy farms that had case of the abortions due to NC infection or had the cattle seropositive to NC, whereas the prevalence was 7.1% (14 of 198 dogs) among the dogs kept in urban areas. In one dog breeder, all 17 Shetland sheepdogs older than 7 months were seropositive, and one pup was diagnosed as neosporosis 2 months before the first serological examination. The antibody titers of the dogs kept at this breeder were almost unchanged for 1.5 years. Serological evidence of the dogs in the dairy farms and urban areas indicates the transmission of NC between dogs and cattle. Also serological results of the dogs in one breeder may suggest the potential horizontal transmission among dogs.     

Giant-cell interstitial pneumonia in a gas station worker

Giant-cell interstitial Pneumonia (GIP) is a very uncommon respiratory disease. The majority of cases of GIP are caused by exposure to cobalt, tungsten and other hard metals. In this report, we describe GIP in a patient who worked in gas station and dealt in propane gas vessels. He presented with clinical features of chronic interstitial lung disease and underwent an open lung biopsy that showed DIP-like reaction with large numbers of intra-alveolar macrophages and numerous large, multinucleated histiocytes which were admixed with the macrophages. Analysis of lung tissue for hard metals was done. Cobalt was the main component of detected hard metals. Corticosteroid therapy was started and he recovered fully.     

Mapping of the binding of platelet-derived growth factor to distinct domains of the basement membrane proteins BM-40 and perlecan and distinction from the BM-40 collagen-binding epitope

Iron is required for cell proliferation of all living species. Moreover, iron excess may be involved in the development of hepatocellular carcinoma. In this study we analyzed the effects of deferoxamine, an iron chelator, on normal porcine hepatocyte proliferation. We confirmed that hepatocytes isolated from young pigs proliferate in the presence of insulin and fetal calf serum as shown by [3H] methyl-thymidine incorporation, presence of mitotic figures and increase in cell number. This was paralleled by nuclear expression of p34cdc2 and its associated histone H1 kinase activity. In the presence of deferoxamine, [3H] methyl-thymidine incorporation, expression of nuclear proteins (p34cdc2 and PCNA) and H1 kinase activity were drastically reduced. In addition, in contrast with control cultures, cells in S-phase were not detected by flow cytometry. These data suggest that iron chelation by deferoxamine can arrest the progression of porcine hepatocytes in the G1 phase of the cell cycle.     

Striatal dopamine dynamics are altered following an intranigral infusion of iron in adult rats

Exercise has a noted effect on skin blood flow and temperature. We aimed to characterize the normal skin temperature response to exercise by thermographic imaging. A study was conducted on ten healthy and active subjects (age=25.8+/-0.7 years) who were exposed to graded exercise for determination of maximal oxygen consumption (VO2 max), and subsequently to constant loads corresponding to 50%, 70%, and 90% of VO2 max. The skin temperature response during 20 min of constant load exercise is characterized by an initial descending limb, an ascending limb and a quasi-steady-state period. For 50% VO2 max, the temperature decrease rate was - 0.0075+/-0.001 degrees C/s during a time interval of 390+/-47 s and the temperature increase rate was 0.0055+/-0.0031 degrees C/s during a time interval of 484+/-99 s. The level of load did not influence the temperature decrease and increase rates. In contrast, during graded load exercise, a continuous temperature decrease of -0.0049+/-0.0032 degrees C/s was observed throughout the test. In summary, the thermographic skin response to exercise is characterized by a specific pattern which reflects the dynamic balance between hemodynamic and thermoregulatory processes.     

Decreased protein kinase C activation mediates inhibitory effect of norathyriol on serotonin-mediated endothelial permeability

We examined the mechanisms of norathyriol on the serotonin-induced increased permeability of rat heart endothelial cell monolayers. The present study showed that the activation of rat heart endothelial cell protein kinase C by phorbol myristate acetate led to the dose-dependent increase in endothelial permeability to albumin, an effect that was inhibited by staurosporine (a protein kinase inhibitor). Staurosporine also attenuated the serotonin-induced increase in permeability. Norathyriol abolished both serotonin- and phorbol myristate acetate-induced permeability. We investigated whether norathyriol, by inhibiting protein kinase C activation, attenuated the serotonin-induced permeability. Immunofluorescence studies demonstrated that norathyriol prevented the redistribution of protein kinase C isozymes following stimulation with serotonin. Western blot analysis showed that norathyriol significantly inhibited the serotonin-induced translocation of the alpha protein kinase C isozyme from the cytosolic to the particulate fraction. In conclusion, norathyriol attenuates the serotonin-induced permeability of rat heart endothelial cells to macromolecules in association with inhibition of protein kinase C activation. This decrease in endothelial cell permeability may be one of the mechanisms for the protective effects of norathyriol against edema formation in response to inflammatory agonists in vivo.