Spontaneous Subcutaneous Sarcoma in a 50-week-old Male Wistar Hannover GALAS Rat

A subcutaneous mass was noted in the abdomen of a 50-week-old male Wistar Hannover GALAS rat. Histologically, the tumor was composed of vimentin-positive small round cells with scant cytoplasm arranged in a trabecular, sheet or pericytoma-like pattern and spindle cells arranged in a bundle pattern and vimentin-negative round cells proliferating in an island-shaped pattern. Argentophilic thin fibers were observed to wrap up the individual cells, and some of the tumor cells showed coexpression of vimentin and cytokeratin that formed juxtanuclear globes in the cytoplasm by double immunohistostaining. Transmission electron microscopy did not reveal any characteristic features suggesting cellular differention toward a specific cell type. Based on these findings, it was difficult to specify the origin, and the tumor was diagnosed as a poorly differentiated mesenchymal tumor and classified as a sarcoma, NOS (not otherwise specified)

BN.MES-Cyba(mes) Congenic Rats Manifest Focal Necrosis with Eosinophilic Infiltration in the Liver without Blood Eosinophilia

The Matsumoto Eosinophilia Shinshu (MES) rat strain develops hereditary blood eosinophilia and eosinophil-related inflammatory lesions in organs due to the mutant Cyba(mes) gene. We hypothesized that a new eosinophilia model with a different phenotype could be established by changing the genetic background of rats. We bred and characterized a congenic strain, in which the mutant Cybames gene was introduced into the background of a BN strain (BN.MES-Cyba(mes)). The congenic rats showed robust proliferation of eosinophils in the bone marrow. Nonetheless, blood eosinophil levels of the rats remained within the normal range. In addition, the rats manifested focal necrosis with eosinophilic infiltration in the liver, a phenotype rarely observed in the original MES rat strain. These results imply the presence of genetic polymorphisms between MES and BN strains which modulate the mobilization of eosinophils to the peripheral circulation and organs. The newly established BN.MES-Cyba(mes) congenic rat strain, together with the original MES strain, will provide useful models for elucidating the molecular genetic mechanisms involved in the development and trafficking of eosinophils.ArticleEXPERIMENTAL ANIMALS. 59(4):469-478 (2010)journal articl

Structural determination, distribution, and physiological actions of ghrelin in the guinea pig

We identified guinea pig ghrelin (gp-ghrelin), and examined its distribution and physiological actions in the guinea-pig. Gp-ghrelin is a 28-amino acid peptide (GASFR SPEHH SAQQR KESRK LPAKI QPR); seven amino acids are different from that of rat ghrelin at positions 2, 5, 10, 11, 19, 21, and 25, which include the conserved region known in mammals. The third serine residue is mainly modified by n-decanoyl acid. Both gp-ghrelin and rat ghrelin increased intracellular Ca^ concentration of HEK293 cells expressing guinea pig growth hormone secretagogue receptor 1a (GHS-R1a), and the affinity of gp-ghrelin was slightly higher than that of rat ghrelin. In addition, gp-ghrelin was also effective in CHO cells expressing rat GHS-R1a with similar affinity to that of rat ghrelin. Gp-ghrelin mRNA was predominantly expressed in the stomach, whereas the expression levels in other organs was low. High levels of GHS-R1a mRNA expression were observed in the pituitary, medulla oblongata, and kidney, while medium levels were noted in the thalamus, pons, olfactory bulb, and heart. Immunohistochemistry identified gp-ghrelin-immunopositive cells in the gastric mucosa and pancreas. Intraperitoneal injection of gp-ghrelin increased food intake in the guinea pig. Gp-ghrelin did not cause any mechanical responses in isolated gastrointestinal smooth muscles in vitro, similar to rat ghrelin. In conclusion, the N-terminal structures that are conserved in mammals were different in gp-ghrelin. Moreover, the functional characteristics of gp-ghrelin, other than its distribution, were dissimilar from those in other Rodentia

BN.MES-Cybames Congenic Rats Manifest Focal Necrosis with Eosinophilic Infiltration in the Liver without Blood Eosinophilia

The Matsumoto Eosinophilia Shinshu (MES) rat strain develops hereditary blood eosinophilia and eosinophil-related inflammatory lesions in organs due to the mutant Cyba(mes) gene. We hypothesized that a new eosinophilia model with a different phenotype could be established by changing the genetic background of rats. We bred and characterized a congenic strain, in which the mutant Cybames gene was introduced into the background of a BN strain (BN.MES-Cyba(mes)). The congenic rats showed robust proliferation of eosinophils in the bone marrow. Nonetheless, blood eosinophil levels of the rats remained within the normal range. In addition, the rats manifested focal necrosis with eosinophilic infiltration in the liver, a phenotype rarely observed in the original MES rat strain. These results imply the presence of genetic polymorphisms between MES and BN strains which modulate the mobilization of eosinophils to the peripheral circulation and organs. The newly established BN.MES-Cyba(mes) congenic rat strain, together with the original MES strain, will provide useful models for elucidating the molecular genetic mechanisms involved in the development and trafficking of eosinophils.ArticleEXPERIMENTAL ANIMALS. 59(4):469-478 (2010)journal articl

Identification of pheasant ghrelin and motilin and their actions on contractility of the isolated gastrointestinal tract

Motilin and ghrelin were identified in the pheasant by molecular cloning, and the actions of both peptides on the contractility of gastrointestinal (GI) strips were examined in vitro. Molecular cloning indicated that the deduced amino acid sequences of the pheasant motilin and ghrelin were a 22-amino acid peptide, FVPFFTQSDIQKMQEKERIKGQ, and a 26-amino acid peptide, GSSFLSPAYKNIQQQKDTRKPTGRLH, respectively. In in vitro studies using pheasant GI strips, chicken motilin caused contraction of the proventriculus and small intestine, whereas the crop and colon were insensitive. Human motilin, but not erythromycin, caused contraction of small intestine. Chicken motilin-induced contractions in the proventriculus and ileum were not inhibited by a mammalian motilin receptor antagonist, GM109. Neither atropine (a cholinergic receptor antagonist) nor tetrodotoxin (a neuron blocker) inhibited the responses of chicken motilin in the ileum but both drugs decreased the responses to motilin in the proventriculus, suggesting that the contractile mechanisms of motilin in the proventriculus was neurogenic, different from that of the small intestine (myogenic). On the other hand, chicken and quail ghrelin did not cause contraction in any regions of pheasant GI tract. Since interaction of ghrelin and motilin has been reported in the house musk shrew, interaction of two peptides was examined. The chicken motilin-induced contractions were not modified by ghrelin, and ghrelin also did not cause any contraction under the presence of motilin, suggesting the absence of interaction in both peptides. In conclusion, both the motilin system and ghrelin system are present in the pheasant. Regulation of GI motility by motilin might be common in avian species. However, absence of ghrelin actions in any GI regions suggests the avian species-related difference in regulation of GI contractility by ghrelin