Ontogenesis of gastrin cells in the pyloric antrum and duodenum of the mouse

Summary Ontogenesis of gastrin cells was studied in the pyloroduodenal mucosa of the mouse using anti-human G17 serum, R-1301, and anti-human G34(1–15) serum, R-2703. R-1301-immunostained cells first appeared in the pyloric mucosa of 14-day-old fetuses. Cells stained with both R-1301 and R-2703 appeared immediately after birth, and gradually increased in number to the adult level. Most R-1301-reactive cells were also reactive to R-2703, whereas some cells that reacted with R-1301 exhibited very weak or no reaction with R-2703. The discrepancy between these two immunoreactivities is discussed.In the duodenum, a considerable number of R-1301-reactive cells were present from the perinatal stage and through out adult development. A few R-2703-reactive cells were seen in the duodenum of young mice but not of the adult.     

Double Infection,Recombination, and Segregation of Two R Factors,R 100 and Rts1, and Their Possible Bearing on the Genetic Structure of R 100

Applying the observation by Yokota et al (1969) that a cell doubly harboring an R factor (R100) and a temperature sensitive R factor (Rts1) produces segregant R factors with various resistance patterns, a total of 271 segregant R factors were obtained. There were 163 resistant to (sul, str, kan), 39 resistant to (sul, str, cml, kan), 62 resistant to (sul, str, tet, kan) and finally 7 resistant to (tet, kan). More than 90% of the former 3 segregants were fi⁺ and the remainder, including all of the (tet, kan) segregants, were fi^?. Some fi^? segregants with the former 3 resistance patterns and all of the (tet, kan) segregants were nontransmissible. All of these segregants were still temperature sensitive. Based upon the results of three experiments; (a) the growth at 43 C to observe linked loss of the kan gene and the genes derived from R 100, (b) a conjugal analysis of the relevant resistant markers, and (c) a transductional analysis of these same markers, several conclusions were made. The 2 R factors both consisting of a circle were supposed to have recombined to form a larger circle which then further resulted in the final formation of smaller circles. The possible bearing of these observations and conclusions on the genetic structure of R 100 was discussed.     

Heligmosomoides polygyrus infection reduces severity of type 1 diabetes induced by multiple low-dose streptozotocin in mice via STAT6- and IL-10-independent mechanisms

Some parasitic helminths are known to protect their hosts from allergic and autoimmune disorders. Here, we tested the effects of a gastrointestinal nematode, Heligmosomoides polygyrus (Hp), on streptozotocin (STZ)-induced type 1 diabetes (T1D) in mice. Hp infection significantly suppressed hyperglycemia induced by multiple low-dose administration of STZ, but did not affect hyperglycemia induced by single high-dose administration of STZ. In the multiple low dose model, Hp infection prevented a decrease in pancreatic islet size. The augmentation of TNF-α and IL-1β expression in the pancreas was abrogated by Hp infection. The genetic absence of IL-10 or STAT6 did not abrogate the anti-hyperglycemic effect of Hp. Hp has a suppressive effect on immune mechanism-mediated experimental T1D via Th2 polarization-independent mechanisms.     

IL-25, IL-33 and TSLP receptor are not critical for development of experimental murine malaria

IL-25, IL-33 and TSLP, which are produced predominantly by epithelial cells, can induce production of Th2-type cytokines such as IL-4, IL-5 and/or IL-13 by various types of cells, suggesting their involvement in induction of Th2-type cytokine-associated immune responses. It is known that Th2-type cytokines contribute to host defense against malaria parasite infection in mice. However, the roles of IL-25, IL-33 and TSLP in malaria parasite infection remain unclear. Thus, to elucidate this, we infected wild-type, IL-25^?/?, IL-33^?/? and TSLP receptor (TSLPR)^?/? mice with Plasmodium berghei (P. berghei) ANKA, a murine malaria strain. The expression levels of IL-25, IL-33 and TSLP mRNA were changed in the brain, liver, lung and spleen of wild-type mice after infection, suggesting that these cytokines are involved in host defense against P. berghei ANKA. However, the incidence of parasitemia and survival in the mutant mice were comparable to in the wild-type mice. These findings indicate that IL-25, IL-33 and TSLP are not critical for host defense against P. berghei ANKA.     

Floating culture promotes the maintenance of hematopoietic stem cells

In this study we examined the effect of the specific gravity of culture medium on the frequency of hematopoietic stem cell (HSC) maintenance. We used a newly developed high-specific-gravity media. Bone marrow cells were isolated and cultured, and HSC activity was evaluated. The number of hematopoietic progenitor/stem cells was markedly higher in the medium with high specific gravity. In high-specific-gravity media, cells did not precipitate, maintenance of HSCs was increased, and there was a concomitant accumulation of beta-catenin. This novel technique for maintaining HSC populations provides an important new tool for studies in regenerative medicine.     

The carbohydrate recognition by cytokines modulates their physiological activities

A variety of cytokines have been reported to be able to recognize specific carbohydrate moieties. To date, the role of carbohydrate recognition in cytokine function has been analyzed for several cytokines, including fibroblast growth factor (FGF), tumor necrosis factor (TNF)-alpha, and interleukin (IL)-2. The FGF family and their receptors have been found to recognize a heparan sulfate proteoglycan, which generates rigid complexes that induce signal transduction. We have found that IL-2 recognizes a high-mannose type glycan on the alpha subunit of the IL-2 receptor as well as a peptide portion of this subunit. Blocking this carbohydrate-IL-2 interaction diminished IL-2-induced signaling and T-cell proliferation. We have also shown that TNF-alpha recognizes the second mannose 6-phosphate diester of the glycan portion of glycosylphosphatidylinositol (GPI)-anchored glycoproteins. Blocking this GPI-anchored glycan-TNF-alpha interaction abrogates TNF-alpha-induced apoptosis. We aim to increase the number of cytokines which modulate their functions through the unique carbohydrate recognition, and open the way to systematically elucidate the biological functions of cytokine-carbohydrate interaction in immune system.     

Six1 controls patterning of the mouse otic vesicle

Six1 is a member of the Six family homeobox genes, which function as components of the Pax-Six-Eya-Dach gene network to control organ development. Six1 is expressed in otic vesicles, nasal epithelia, branchial arches/pouches, nephrogenic cords, somites and a limited set of ganglia. In this study, we established Six1-deficient mice and found that development of the inner ear, nose, thymus, kidney and skeletal muscle was severely affected. Six1-deficient embryos were devoid of inner ear structures, including cochlea and vestibule, while their endolymphatic sac was enlarged. The inner ear anomaly began at around E10.5 and Six1 was expressed in the ventral region of the otic vesicle in the wild-type embryos at this stage. In the otic vesicle of Six1-deficient embryos, expressions of Otx1, Otx2, Lfng and Fgf3, which were expressed ventrally in the wild-type otic vesicles, were abolished, while the expression domains of Dlx5, Hmx3, Dach1 and Dach2, which were expressed dorsally in the wild-type otic vesicles, expanded ventrally. Our results indicate that Six1 functions as a key regulator of otic vesicle patterning at early embryogenesis and controls the expression domains of downstream otic genes responsible for respective inner ear structures. In addition, cell proliferation was reduced and apoptotic cell death was enhanced in the ventral region of the otic vesicle, suggesting the involvement of Six1 in cell proliferation and survival. In spite of the similarity of otic phenotypes of Six1- and Shh-deficient mice, expressions of Six1 and Shh were mutually independent.     

Suppression of immune induction of collagen-induced arthritis in IL-17-deficient mice

Interleukin-17 is a T cell-derived proinflammatory cytokine. This cytokine is suspected to be involved in the development of rheumatoid arthritis (RA) because this cytokine expression is augmented in synovial tissues of RA patients. The pathogenic roles of IL-17 in the development of RA, however, still remain to be elucidated. In this study, effects of IL-17 deficiency on collagen-induced arthritis (CIA) model were examined using IL-17-deficient mice (IL-17(-/-) mice). We found that CIA was markedly suppressed in IL-17(-/-) mice. IL-17 was responsible for the priming of collagen-specific T cells and collagen-specific IgG2a production. Thus, these observations suggest that IL-17 plays a crucial role in the development of CIA by activating autoantigen-specific cellular and humoral immune responses.