Cholera Toxin Enhances Vaccine-Induced Protection against Mycobacterium Tuberculosis Challenge in Mice

Interleukin (IL)-17 is emerging as an important cytokine in vaccine-induced protection against tuberculosis disease in animal models. Here we show that compared to parenteral delivery, BCG delivered mucosally enhances cytokine production, including interferon gamma and IL-17, in the lungs. Furthermore, we find that cholera toxin, delivered mucosally along with BCG, further enhances IL-17 production by CD4⁺ T cells over mucosal BCG alone both in the lungs and systemically. This boosting effect of CT is also observed using a vaccine regimen of BCG followed by the candidate vaccine MVA85A. Using a murine Mycobacterium tuberculosis (M.tb) aerosol challenge model, we demonstrate the ability of cholera toxin delivered at the time of a priming BCG vaccination to improve protection against tuberculosis disease in a manner at least partially dependent on the observed increase in IL-17. This observed increase in IL-17 in the lungs has no adverse effect on lung pathology following M.tb challenge, indicating that IL-17 can safely be boosted in murine lungs in a vaccine/M.tb challenge setting.     

On the computation of substrate levels in perfused tissues

The recent development of experimental techniques to study the isolated perfused heart and brain have renewed interest in the mathematical modeling of capillary-tissue structures. A new analytical representation is developed for the Krogh cylinder model for blood-tissue structures, and a scheme is presented for determining an asymptotic series approximation for this solution. This solution is explored for model parameters of experimental interest, and the contribution and effect of axial diffusion is demonstrated.     

Isolation and characterization of a cDNA encoding rat cationic trypsinogen

A cDNA encoding rat cationic trypsinogen has been isolated by immunoscreening from a rat pancreas cDNA library. The protein encoded by this cDNA is highly basic and contains all of the structural features observed in trypsinogens. The amino acid sequence of rat cationic trypsinogen is 75% and 77% homologous to the two anionic rat trypsinogens. The homology of rat cationic trypsinogen to these anionic trypsinogens is lower than its homology to other mammalian cationic trypsinogens, suggesting that anionic and cationic trypsins probably diverged prior to the divergence of rodents and ungulates. The most unusual feature of this trypsinogen is the presence of an activation peptide containing five aspartic acid residues, in contrast to all other reported trypsinogen activation peptides which contain four acidic amino acid residues. Comparisons of cationic and anionic trypsins reveal that the majority of the charge changes occur in the C-terminal portion of the protein, which forms the substrate binding site. Several regions of conserved charge differences between cationic and anionic trypsins have been identified in this region, which may influence the rate of hydrolysis of protein substrates.     

Serum cortisol, glucose and lipids in plaice (Pleuronectes platessa L.) exposed to starvation and aquarium stress

Plaice were maintained in the aquarium (11-12 degrees C) during May for 15 days without feeding. Within 48 hr, there was a decline in serum total lipids (P less than 0.001), phospholipids (P less than 0.01), triglycerides (P less than 0.001), cortisol (P less than 0.01) and glucose (P less than 0.001), but an increase in nonesterified fatty acids (NEFA; P less than 0.01). There was a significant inverse correlation between NEFA and glucose over 15 days (P less than 0.001) and between NEFA and cortisol over the first 5 days (P less than 0.01). Cortisol and glucose showed a significant correlation over 15 days (P less than 0.01). Serum cortisol and glucose were not apparently affected by starvation. Only cortisol provided a sensitive indicator of aquarium disturbance. Exposure of the fish to agitation or reduced O2 for 1 hr significantly elevated cortisol (P less than 0.001) but only the latter treatment elevated glucose (P less than 0.01); neither treatment affected the lipids.     

Possible Loss of Length Conservation and Reciprocity during Recombination or Conversion in Tandem Arrays

Recombination or conversion between arrays of repeated sequences need not be conservative for length because two single strands of DNA from one chromatid may form heteroduplexes in different registers on the other participating duplex. This can cause an overall change in repeat number. Loss of length conservation is equally possible whether models of recombination initiated by single-strand transfer or double-strand break are applicable. Length changing conversion will frequently produce a characteristic insertion within a deletion, often appearing as a double deletion such as are frequently found in new variants of human minisatellite MS32. There is no apparent means of preserving parity during length-changing conversion or recombination, and if the changes are biased then the overall copy number will increase or decrease according to that bias. The observation that arrays persist suggests that any bias in these arrays will be toward gains. An equilibrium may be reached where gains, which may be largely independent of array length, equal losses from the array-length-dependent processes of intrachromatid recombination and repeated unequal sister chromatid exchanges.     

Isolation of substances with vascular permeability-increasing activity from the skin of the plaice (Pleuronectes platessa L.)

A methanolic extract of plaice skin, from which lipids had been removed, was chromatographed on alumina, eluted with decreasing concentrations of ethanol. Only the 60% ethanol fraction exhibited smooth muscle activity, with bradykinin-like properties. The 20% ethanol fraction increased vascular permeability in rat skin, as measured by dye-leakage. This was not due to the degranulation of mast cells. Intradermal injection of either fraction into the plaice caused localized erythema.     

The expression of alpha(1)-acid glycoprotein mRNA during rat development. High levels of expression in the decidua

During the acute phase response to inflammation the plasma concentration of some proteins, such as alpha(1-acid glycoprotein (AGP), increases dramatically. Since breakdown and remodeling of tissue is common to both nidation and inflammation we studied the tissue distribution and regulation of AGP mRNA levels during the embryonic development of the rat. High levels of mRNA coding for AGP were detected in the placenta during early fetal development. Expression of this mRNA was confined to the decidua and was first observed approximately 1 day after implantation when proliferation of the decidua is already well advanced. Maximum levels were attained about 5 days after implantation, after which the levels decreased rapidly. In contrast to the high levels of AGP mRNA in the decidua only very low levels were detected in fetal liver and visceral yolk sac, and there was only a small increase in the levels in maternal liver. Corticosteroid hormone responsiveness of AGP mRNA synthesis by hepatocytes appeared 3 days before birth. It is likely that the synthesis of AGP by the cells of the decidua is important in establishing the precisely controlled interaction between mother and embryo during nidation.