Origins of the projections of the superior colliculus to the dorsal lateral geniculate nucleus and the pulvinar in the rabbit

The origins of the projections of the superior colliculus to the dorsal lateral geniculate nucleus and to the pulvinar in Dutch-belted rabbits were investigated using horseradish peroxidase (HRP) methods. Following injections of HRP in the dorsal lateral geniculate nucleus, retrogradely labeled neurons were found in the upper two-thirds of the stratum griseum superficiale of the ipsilateral superior colliculus. Most of the labeled somata were spindle-shaped, and their major axes tended to be perpendicular to the surface of the superior colliculus. In contrast, following injections of the pulvinar, labeled neurons were found in the lower third of the ipsilateral stratum griseum superficiale. In these cases, the labeled somata were larger than those labeled following dorsal lateral geniculate injections and were multipolar in shape.     

Effects of theophylline,terbutaline, and prednisone on antigen-induced bronchospasm and mediator release

Eleven subjects demonstrating clinical, skin, and inhalation sensitivity to grass or ragweed pollen underwent serial inhalation challenges, with and without orally administered theophylline, terbutaline, and prednisone. Comparisons of antigen sensitivity and mediator release were made during these challenges. All three drugs significantly reduced antigen sensitivity (PD₂₀ inhalation units increasing from 670 to ≧ 3,280). Peak plasma histamine levels after antigen challenge decreased from 11.4 ng/ml to ≦ 3.4 ng/ml during all drug administrations. Similarly, the percent increase in serum neutrophil chemotactic activity (NCA) also decreased, from 96% to ≦ 36% during drug administrations. However, even at antigen doses resulting in bronchospasm during drug administration the systemic appearance of NCA and histamine were reduced. We conclude that prednisone, theophylline, and terbutaline significantly reduce antigen-induced bronchospasm and mediator release. The occurrence of bronchospasm despite the inhibition of histamine and NCA suggests either that the local concentration of these mediators are critical or that other mediators produce the bronchospasm observed.     

Lactobacillus acidophilus Induces a Strain-specific and Toll-Like Receptor 2–Dependent Enhancement of Intestinal Epithelial Tight Junction Barrier and Protection Against Intestinal Inflammation

Defective intestinal tight junction (TJ) barrier is an important pathogenic factor of inflammatory bowel disease. To date, no effective therapies that specifically target the intestinal TJ barrier are available. The purpose of this study was to identify probiotic bacterial species or strains that induce a rapid and sustained enhancement of intestinal TJ barrier and protect against the development of intestinal inflammation by targeting the TJ barrier. After high-throughput screening of >20 Lactobacillus and other probiotic bacterial species or strains, a specific strain of Lactobacillus acidophilus, referred to as LA1, uniquely produced a marked enhancement of the intestinal TJ barrier. LA1 attached to the apical membrane surface of intestinal epithelial cells in a Toll-like receptor (TLR)-2–dependent manner and caused a rapid increase in enterocyte TLR-2 membrane expression and TLR-2/TLR-1 and TLR-2/TLR-6 hetero-complex–dependent enhancement in intestinal TJ barrier function. Oral administration of LA1 caused a rapid enhancement in mouse intestinal TJ barrier, protected against a dextran sodium sulfate (DSS) increase in intestinal permeability, and prevented the DSS-induced colitis in a TLR-2– and intestinal TJ barrier–dependent manner. In conclusion, we report for the first time that a specific strain of LA causes a strain-specific enhancement of intestinal TJ barrier through a novel mechanism that involves the TLR-2 receptor complex and protects against the DSS-induced colitis by targeting the intestinal TJ barrier.

Intestinal epithelial tight junctions (TJs) are the apical-most junctional complexes and act as a functional and structural barrier against the paracellular permeation of harmful luminal antigens, which promote intestinal inflammation.¹ The increased intestinal permeability caused by defective intestinal epithelial TJ barrier or a leaky gut is an important pathogenic factor that contributes to the development of intestinal inflammation in inflammatory bowel disease (IBD) and other inflammatory conditions of the gut, including necrotizing enterocolitis and celiac disease.^2,3 Clinical studies in patients with IBD have found that a persistent increase in intestinal permeability after clinical remission is predictive of poor clinical outcome and early recurrence of the disease, whereas normalization of intestinal permeability correlates with a sustained long-term clinical remission.4, 5, 6 Accumulating evidence has found that a defective intestinal TJ barrier plays an important role in exacerbation and prolongation of intestinal inflammation in IBD. Currently, no effective therapies that specifically target the tightening of the intestinal TJ barrier are available.Intestinal microbiota play an important role in modulating the immune system and in the pathogenesis of intestinal inflammation.⁷ Patients with IBD have bacterial dysbiosis in the gut, characterized by a decrease in bacterial diversity and an aberrant increase in some commensal bacteria, which are an important factor in the pathogenesis of intestinal inflammation.^8,9 Normal microbial flora of the gastrointestinal tract consists both of bacteria that are known to have beneficial effects (probiotic bacteria) on intestinal homeostasis and bacteria that could potentially have detrimental effects on gut health (pathogenic bacteria).¹⁰ The modulation of intestinal microflora affects the physiologic and pathologic states in humans and animals. For example, fecal transplantation from healthy, unaffected individuals to patients with refractory Clostridium difficile colitis is curative in up to 94% of the treated patients, and transfer of stool microbiome from obese mice induces obesity in previous lean mice, whereas transfer of microbiome from lean mice preserves the lean phenotype.11, 12, 13 The beneficial effects of gut microbiota are host and bacterial species-specific.¹⁴ Although multiple studies indicate that some commensal bacteria play a beneficial role in gut homeostasis by preserving or promoting the intestinal barrier function, because of conflicting reports, it remains unclear which probiotic species cause a persistent predictable enhancement in the TJ barrier and could be used to treat intestinal inflammation by targeting the TJ barrier. For example, some studies suggest that Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus plantarum, or Lactobacillus rhamnosus cause a modest enhancement in the intestinal epithelial TJ barrier, whereas others have found minimal or no effect of these probiotic species on the intestinal TJ barrier.15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 The major aim the current study was to perform a high-throughput screening of Lactobacillus and other bacterial species to identify probiotic species that induce a rapid, predictable, and marked increase in the intestinal epithelial TJ barrier and protect against the development of intestinal inflammation by preserving the intestinal TJ barrier.In the studies described herein, most of the probiotic species tested (>20 species or strains) had a modest or minimal effect on intestinal TJ barrier function. L. acidophilus uniquely caused a rapid and marked increase in intestinal TJ barrier function. Further analysis indicated that the effect of L. acidophilus was strain-specific, limited to a specific strain of L. acidophilus, and did not extend to other L. acidophilus strains. The L. acidophilus enhancement of the intestinal TJ barrier was mediated by live bacterial-enterocyte interaction that involved Toll-like receptor (TLR)-2 heterodimeric complexes on the apical membrane surface of intestinal epithelial cells. Our animal studies also found that L. acidophilus causes a marked enhancement in mouse intestinal barrier function and protects against the dextran sodium sulfate (DSS)–induced colitis by preserving and augmenting the mouse intestinal barrier function in a strain-specific manner.     

Isolation and characterization of entomopox virions from virus-containing inclusions of Amsacta moorei (Lepidoptera: Arctiidae)

Preparations of Amsacta moorei entomopox virions were obtained from virus-containing inclusions (VCI) by using a carbonate-thioglycolate solution (pH 10.7–11.5). The virions possessed a uniform coat (“halo”) surrounding the viral envelope and exhibited an RNA polymerase activity. The “halo” could be removed by prolonged exposure to the carbonate-thioglycolate solution. Virions obtained by this treatment, however, possessed low infectivity and no detectable RNA polymerase activity. Removal of the “halo” by trypsin resulted in virions which possessed RNA polymerase activity and relatively high infectivity.Preparations of particles with and without the “halo” were similar in percent DNA, protein per OD₂₆₀, number of particles per OD₂₆₀, and RNA polymerase activity. Particles without the “halo,” however, were less dense (1.262 g/cm³) in CsCl than those with the “halo” (1.282 g/cm³) and 15–45 times more infective.Parallel studies of “nonhaloed” Amsacta virions (trypsin-treated) and vaccinia virions showed that both viruses contained similar amounts of protein per OD₂₆₀, but Amsacta virions contained only 36% of the DNA found in vaccinia.     

Histologic studies of human skin test responses to ragweed and compound 48/80: III. Effects of alternate-day steroid therapy

Our previous studies have shown depressed eosinophil responses in skin test reactions to pollen antigens and compound 48/80 in those just completing a 1-wk course of daily steroids. Wheal reactions were unaffected. In this study, 6 ragweed-sensitive atopic subjects were studied before and on the seventh day (“day on”) and day 8 (“day off”) of a course of alternate-day steroids. Blood neutrophil levels rose on day 7 and were similar to baseline on day 8, whereas blood eosinophil levels were significantly reduced on both days 7 and 8. Neutrophil responses in skin test reactions were depressed on day 7 and normal on day 8. In contrast, the tissue eosinophil responses were depressed significantly, and to similar degree, on both days 7 and 8. These findings are of potential significance in evaluating the clinical effects of steroids in allergic diseases.