Safety and immunogenicity of three doses of an eleven-valent diphtheria toxoid and tetanus protein – conjugated pneumococcal vaccine in Filipino infants

Background  

An 11-valent pneumococcal conjugate vaccine could provide significantly larger reduction in pneumococcal disease burden than the currently available 7-valent vaccine formulation in many countries.     

Identifying a differential equation for lip motion

A second order homogeneous differential equation is fitted to lip trajectories during speech at fast, normal, and slow speaking rates. The objective is to characterize lip motion in terms of biomechanical parameters such as stiffness, damping, and applied external forces. The results show that, at fast speaking rates, the lip behaves like a simple mass-spring oscillator moving at its natural frequency, and with low variability across repetitions. At slow speaking rates, on the other hand, the lip is under a stronger external control to conform to the required trajectory, which introduces a larger variability across repetitions. The case of normal rate falls between the fast and slow rate cases.     

Expression of gelatinise/type IV collagenase in tumor necrosis correlates with cell detachment and tumor invasion

We have previously observed that acellular extracts from necrotic areas (NE) of the non-metastatic murine mammary adenocarcinoma M3, enhancein vitro cell detachment and spontaneous lung metastases. In the present study, using different proteinase inhibitors along with NE, only the calcium chelator EDTA could significantly abrogate the enhanced cell detachment from M3 produced by NE. The typical cleavage products of type IV collagenase were detected inside the tumor necrotic area, mainly in association with necrobiotic cells, as evaluated by Western blot analysis and immunohistochemical assays. Zymography revealed the presence of 72- and 92-kDa gelatinise/type IV collagenase in NE. Moreover, NE increased thein vitro invasive ability of cultured M3 cells. The use of specific antibodies against both 72- and 92-kDa type IV collagenases in the invasion assay showed that only the latter was able to revert the enhanced invasiveness to the baseline. It can be concluded that tumor necrosis is an important source of gelatinise/type IV collagenase, mainly in its 92 kDa form, and plays a major role in tumor invasion.     

Dopamine reduces odor- and elevated-K(+)-induced calcium responses in mouse olfactory receptor neurons in situ

Although D2 dopamine receptors have been localized to olfactory receptor neurons (ORNs) and dopamine has been shown to modulate voltage-gated ion channels in ORNs, dopaminergic modulation of either odor responses or excitability in mammalian ORNs has not previously been demonstrated. We found that <50 microM dopamine reversibly suppresses odor-induced Ca2+ transients in ORNs. Confocal laser imaging of 300-microm-thick slices of neonatal mouse olfactory epithelium loaded with the Ca(2+)-indicator dye fluo-4 AM revealed that dopaminergic suppression of odor responses could be blocked by the D2 dopamine receptor antagonist sulpiride (<500 microM). The dopamine-induced suppression of odor responses was completely reversed by 100 microM nifedipine, suggesting that D2 receptor activation leads to an inhibition of L-type Ca2+ channels in ORNs. In addition, dopamine reversibly reduced ORN excitability as evidenced by reduced amplitude and frequency of Ca2+ transients in response to elevated K(+), which activates voltage-gated Ca2+ channels in ORNs. As with the suppression of odor responses, the effects of dopamine on ORN excitability were blocked by the D2 dopamine receptor antagonist sulpiride (<500 microM). The observation of dopaminergic modulation of odor-induced Ca2+ transients in ORNs adds to the growing body of work showing that olfactory receptor neurons can be modulated at the periphery. Dopamine concentrations in nasal mucus increase in response to noxious stimuli, and thus D2 receptor-mediated suppression of voltage-gated Ca2+ channels may be a novel neuroprotective mechanism for ORNs.     

Cross‐Species Comparison of Metabolite Profiles in Chemosensory Epithelia: An Indication of Metabolite Roles in Chemosensory Cells

Comparative studies of chemosensory systems in vertebrates and invertebrates have greatly enhanced our understanding of anatomical and physiological constraints of chemical detection. Immunohistochemical comparisons of chemosensory systems are difficult to make across species due to limited cross‐reactivity of mammalian‐based antibodies. Immunostaining chemosensory tissues with glutaraldehyde‐based antibodies generated against small metabolites in combination with hierarchical cluster analyses provide a novel approach for identifying and classifying cell types regardless of species. We used this “metabolite profiling” technique to determine whether metabolite profiles can be used to identify cell classes within and across different species including mouse, zebrafish, lobster and squid. Within a species, metabolite profiles for distinct cell classes were generally consistent. We found several metabolite‐based cell classifications that mirrored function or receptor protein‐based classifications. Although profiles of all six metabolites differed across species, we found that specific metabolites were associated with certain cell types. For example, elevated levels of glutathione were characteristic of nonsensory cells from vertebrates, suggesting an antioxidative role in non‐neuronal cells in sensory tissues. Collectively, we found significantly different metabolite profiles for distinct cell populations in chemosensory tissue within all of the species studied. Based on their roles in other systems or cells, we discuss the roles of L‐arginine, L‐aspartate, L‐glutamate, glycine, glutathione, and taurine within chemosensory epithelia. Anat Rec, 291:410–432, 2008. © 2008 Wiley‐Liss, Inc.     

Effects of neuroblastoma tumor gangliosides on platelet adhesion to collagen

Gangliosides, sialic acid-containing glycosphingolipids, enhance tumor formation in experimental animals and are associated with tumor progression and metastasis in humans. The mechanism(s) for this activity is (are) unknown. One possibility is enhanced platelet activation, since the interaction of platelets with tumor cells contributes to tumor cell arrest in the vascular compartment. We have previously shown that neuroblastoma tumor gangliosides (NBTG) enhance platelet adenosine triphosphate (ATP) secretion, aggregation, and adhesion. We determined that these NBTG effects are specific for collagen and are mediated through an (( integrin-dependent mechanism. This report describes the effects of NBTG on a physiologically relevant model of collagen-( interaction. Platelet adhesion to immobilized native collagen fibers similar to those found in the extracellular matrix of blood vessels was determined. Platelet adhesion is enhanced by NBTG in a concentration-dependent manner. Incubation with concentrations of 1 and 10 m NBTG increased platelet adhesion by 9% and 52%, respectively, compared to less than 1% in controls not incubated with gangliosides (P = 0.001 and P < 0.0001, respectively). In addition to increasing the number of adherent platelets, NBTG promoted more rapid attachment. In NBTG-incubated platelets, platelet adhesion began after a 5-min lag phase and was maximal at 30 min compared to a 20-min lag phase and maximal adhesion at 60 min for control platelets. At 30 min this difference was significant (P = 0.017); however, by 120 min there was no difference between NBTG and controls (P = 0.259). NBTG also induces platelet adhesion at collagen concentrations (0.1 g) that failed to support adhesion of control platelets. These effects of NBTG require Mg or Mn ions but are not supported by Zn or Ca ions. Furthermore, preincubation of platelets with a blocking antibody (6F1) to the integrin collagen receptor ( abrogates all of the effects of NBTG. These results indicate that tumor gangliosides enhance platelet adhesion to extracellular matrix collagen and promote rapid stabilization of the collagen-(( interaction, the initial steps in platelet activation.