Nucleotide-binding oligomerization domain 1 acts in concert with the cholecystokinin receptor agonist, cerulein, to induce IL-33-dependent chronic pancreatitis.

Nucleotide-binding oligomerization domain 1 (NOD1) fulfills important host-defense functions via its responses to a variety of gut pathogens. Recently, however, we showed that in acute pancreatitis caused by administration of cholecystokinin receptor (CCKR) agonist (cerulein) NOD1 also has a role in inflammation via its responses to gut commensal organisms. In the present study, we explored the long-term outcome of such NOD1 responsiveness in a new model of chronic pancreatitis induced by repeated administration of low doses of cerulein in combination with NOD1 ligand. We found that the development of chronic pancreatitis in this model requires intact NOD1 and type I IFN signaling and that such signaling mediates a macrophage-mediated inflammatory response that supports interleukin (IL)-33 production by acinar cells. The IL-33, in turn, has a necessary role in the induction of IL-13 and TGF-ß1, factors causing the fibrotic reaction characteristic of chronic pancreatitis. Interestingly, the Th2 effects of IL-33 were attenuated by the concomitant type I IFN response since the inflammation was marked by clear increases in IFN-γ and TNF-α production but only marginal increases in IL-4 production. These studies establish chronic pancreatitis as an IL-33-dependent inflammation resulting from synergistic interactions between the NOD1 and CCKR signaling pathways.

Optimal dispersal range and seed size in a stable environment

The evolutionary stable (ESS) dispersal range for annual plants is studied in a stable environment when there is a trade -off between seed survivability and dispersal range via seed size. Larger seed size is more beneficial in the competition for safe sites, but likely to be dispersed a shorter distance and to suffer competition among siblings. Previously Hamilton & May found that dispersal can be adaptive in a stable environment to reduce competition among sibs, but they assumed that dispersers were likely to enter all the patches equally-this is not suitable for many terrestrial plants with limited dispersal range. In this article I discuss the evolution of dispersal range for wind dispersed seeds when dispersal range is tightly coupled with seed size. I assume that the density of dispersed seed follows a two-dimensional normal distribution function, with variance decreasing with seed size. Due to the trade-off between the seed number and the survivability of a seedling offspring, there is a seed size &wtilde; that maximizes the product of the two quantities. This is the optimal seed size when size-dependent dispersal is neglected. The ESS seed size considering the size-dependent dispersal w* is also calculated by neglecting the effect of spatial clumping of relatives. Under the environment unfavorable for seed dispersal, the ESS seed size w* can be much smaller than the optimal seed size &wtilde;, but there is a lower limit for the ESS dispersal range even in the extremely sticky environment. Even if the dependency of seed survivability on the seed size is so weak that the cost of long-range dispersal is small, the ESS seed dispersal range cannot become very large. These results are confirmed by individual-based computer simulations with more realistic assumptions considering spatial clumping of non-sib relatives.Copyright 1998 Academic Press Limited

Population persistence and spatially limited social interaction.

We investigate the persistence of a population composed of socially interacting individuals living in a lattice structured habitat and the effect of spatially limited social interaction, reproduction, and migration. Both cooperative interaction (enhancing the survivorship of neighboring individuals) and competitive interaction (reducing it) are examined. Mathematical analysis based on pair approximation (or doublet decoupling approximation) and computer simulation are used. Results are: If migration rate is not very large, the population tends to form clusters of individuals (clumped distribution) due to spatially limited reproduction. Although cooperative interaction is more effective in a spatially structured population, the population is more difficult to persist than in the corresponding population without spatial structure, because the shortage of nearest neighbor vacant sites reduces reproduction. Migration of individuals reduces the clumping of the spatial pattern. Pair approximation predicts the equilibrium density fairly accurately when the predicted density is sufficiently high (i.e., more than 40% sites are occupied). If the predicted density is low however, the pair approximation overestimates the equilibrium population level. To overcome this disagreement, we examined improved pair approximation.

Establishment and characterization of human myelomonocytic (TYS) and histiocytic (TYH) cell lines.

Two human hematopoietic cell lines (TYS and TYH) with monocytic characteristics were derived from the peripheral blood of a patient with acute myelomonocytic leukemia and of another with a follicular large-cell type of malignant lymphoma. The TYS cells, derived from the leukemia patient, revealed a monocytic appearance with microvilli at one side and had many granules and vacuoles. They showed strongly positive reactions with alpha-NBE, NASDAE, and AcP, and were reactive with monoclonal antibodies such as OKlal, 12 and Bl. The TYS cells, which phagocytized carbon particles and antibody-coated SRBC but not latex particles, released lysosomal enzymes and tumoricidal factor into the supernatant. The TYH cells, derived from the malignant lymphoma patient, had abundant cytoplasm and pseudopods detectable by electron microscopy with a monocytoid appearance and virus-like particles in the cytoplasm. They showed strongly positive reactions with alpha-NBE, NASDAE and beta-Gase, but no reactivity with monoclonal antibodies or with surface markers except Fc gamma-R. TYH cells phagocytized latex particles very well. Two different human monocyte-histiocyte lineages were thus established. During culture, the TYS and TYH cells maintained their characteristics over 28 and 16 months of passage, respectively.

Regulation of allergic reaction by aerobic Corynebacterium equi extract, CEF. III. Inhibition of histamine release from rat peritoneal mast cells.

Effects of a water soluble fraction of Corynebacterium equi (CEF) on the histamine release from rat peritoneal mast cells (RPMC) were investigated. The treatment of RPMC with CEF resulted in a significant inhibition of the histamine release from RPMC which was induced by IgE antibody-antigen interaction as well as nonimmunological histamine liberators. CEF was much more effective in inhibition of IgE-mediated histamine release and compound 48/80 or polymyxin B-induced histamine release when the mast cells were treated with CEF prior to the incubation with the antigen or the liberators. In contrast, CEF was equally effective in inhibition of the histamine release by concanavalin A with phosphatidyl serine when the mast cells were treated with CEF prior to or simultaneously with the liberator. Evidence was also presented that CEF inhibits degranulation of mesenteric mast cells induced by immunological as well as nonimmunological mechanisms.

Degradation of intracellular DNA in KB cells infected with cyt mutants of human adenovirus type 12.

A group of mutants (cyt mutants) with much reduced oncogenicity was isolated from the highly oncogenic human adenovirus type 12 (Takemori et al., Virology 36: 575-586, 1968). These mutants induce extensive cellular destruction during lytic infection of human cells and produce low yields of virions. We report here that human KB cells infected with cyt mutants synthesized a reduced amount of viral DNA as compared with cells infected with the parental virus. Furthermore, the newly synthesized viral and cellular DNAs were extensively degraded in mutant-infected cells. Viral DNA was first synthesized as complete genome size, and most of it was degraded to subgenomic size within 6 h after synthesis. This virus-induced DNA degradation function, as well as the low yield of virions, was prevented by co-infection with the parental virus.

Regulation of allergic reaction by aerobic Corynebacterium equi extract, CEF. I. Antigen-nonspecific suppression of reaginic antibody response in mice.

The effect of a water-soluble fraction (CEF) that was prepared from an extract of Corynebacterium equi on primary reaginic antibody formation was studied in Balb/c mice. Mice were immunized with a hapten carrier (DNP-OVA) and received intraperitoneal injections of CEF 7 and 2 days prior to, or 2 and 7 days after the immunization. PCA titers of both antihapten (DNP) and anticarrier (OVA) antibodies of IgE class were reduced significantly by the CEF treatment. Evidence was presented in adoptive transfer experiments that the number of IgE-producing cells in the CEF-treated mice was lower than that of controls. Suppression of IgG1 anti-DNP antibody formation was also achieved by the CEF treatment. Formation of IgG1 anti-OVA antibodies, however, was not suppressed significantly by the treatment. The suppressive activities of CEF were shown to be dose-dependent, but timing of CEF administration did not appear critical.

Regulation of allergic reactions by aerobic Corynebacterium equi extract, CEF. II. Inhibition of Heterologous PCA and antigen-induced histamine release in rats.

A water-soluble fraction (CEF) obtained from Corynebacterium equi was administered intradermally or intravenously into Sprague-Dawley rats. Passive cutaneous anaphylaxis (PCA) was elicited in these rats along with the controls by sensitization with mouse anti-DNP serum and challenge with the corresponding antigen. PCA reactions were markedly inhibited by the pretreatments of the rats with CEF. Similar treatments of the animals 2-4h after the sensitization did not inhibit PCA. Inhibitory activity of CEF in the pretreated animals was shown to be dose-dependent. Incubation of rat peritoneal mast cells with CEF effectively blocked the binding of murine IgE antibodies to the cells as evidenced by the failure of the treated cells to bind the antibodies. Furthermore, antigen-induced histamine release from rat mast cells, which were sensitized with murine IgE antibodies, was reduced significantly by CEF treatment of the cells prior to the sensitization. Results of this study indicated that CEF inhibits the PCA in rats, presumably by blocking the binding of heterocytotropic antibodies to Fc receptor of mast cells.

Evidence for a naturally occurring anti-spermine antibody in normal rabbit serum.

Normal rabbit serum contains an IgG-like component(s) that binds spermine as well as other polyamines. This molecule(s) has the same physicochemical properties as anti-spermine antibody obtained from rabbits immunized with spermine-thyroglobulin conjugates. However, the polyamines-binding IgG-like molecule(s), unlike anti-spermine antibody, is incapable either of precipitating a spermine-bovine serum albumin complex or of binding to a spermine-Sepharose column. These results suggest the existence of a naturally occurring anti-polyamine antibody that may have defective antibody functions.

Structure and function of adenovirus type 12 defective virions.

Purified human adenovirus type 12 preparations contain defective virions with a lighter density. These defective virions were isolated, and their biological functions and DNA were characterized. They can induce early and late antigens in infected cells and tumors in newborn hamsters with similar efficiency as complete virions. The majority of the DNA molecules from light virions contain deletions mapping near 16% from the left-hand end of the genome. Mechanisms for the generation of these molecules are discussed.

Potential hazards of uranium and its compounds in electron microscopy: a brief review.

Uranium and its compounds are radioactive and highly toxic. Although well documented in the specialized literature the potential hazards are little known among microscopists. Labelling of these compounds does not indicate potential hazards sufficiently.

Comparative studies on functions of human adenovirus type 12 and its low oncogenic mutant virions.

Physical and biological properties of highly oncogenic human adenovirus type 12 were compared with a low oncogenic mutant (cyt mutant). Parental and cyt mutant virions had very similar density and DNA size. However, the parental strain virion preparations contained a much higher proportion of defective virions (capable of cell killing, but not able to induce T- or V-antigen) than cyt mutant stock. It was also found that cyt mutant had a reduced virus yield in several human cell lines compared with the parental strain.