The INHAND Project (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) is a joint initiative of the Societies of Toxicologic Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP), and North America (STP) to develop an internationally accepted nomenclature for proliferative and nonproliferative lesions in laboratory animals. The purpose of this publication is to provide a standardized nomenclature and differential diagnosis for classifying microscopic lesions observed in the male reproductive system of laboratory rats and mice, with color microphotographs illustrating examples of some lesions. The standardized nomenclature presented in this document is also available for society members electronically on the Internet (http://goreni.org). Sources of material included histopathology databases from government, academia, and industrial laboratories throughout the world. Content includes spontaneous and aging lesions as well as lesions induced by exposure to test materials. A widely accepted and utilized international harmonization of nomenclature for lesions of the male reproductive system in laboratory animals will decrease confusion among regulatory and scientific research organizations in different countries and provide a common language to increase and enrich international exchanges of information among toxicologists and pathologists.

The molecular mechanism responsible that determines cell fate after mitotic slippage is unclear. Here we investigate the post-mitotic effects of different mitotic aberrations—misaligned chromosomes produced by CENP-E inhibition and monopolar spindles resulting from Eg5 inhibition. Eg5 inhibition in cells with an impaired spindle assembly checkpoint (SAC) induces polyploidy through cytokinesis failure without a strong anti-proliferative effect. In contrast, CENP-E inhibition causes p53-mediated post-mitotic apoptosis triggered by chromosome missegregation. Pharmacological studies reveal that aneuploidy caused by the CENP-E inhibitor, Compound-A, in SAC-attenuated cells causes substantial proteotoxic stress and DNA damage. Polyploidy caused by the Eg5 inhibitor does not produce this effect. Furthermore, p53-mediated post-mitotic apoptosis is accompanied by aneuploidy-associated DNA damage response and unfolded protein response activation. Because Compound-A causes p53 accumulation and antitumour activity in an SAC-impaired xenograft model, CENP-E inhibitors could be potential anticancer drugs effective against SAC-impaired tumours.

Histochemical, lectin-histochemical and morphometrical studies were carried out on intestinal goblet cells of 8-week-old germfree (GF) and conventional (CV) mice of the BALB/c strain. Except for the reactivity of cecal goblet cells to Dolichos biflorus agglutinin (DBA) and Ulex europeus-I agglutinin (UEA-I), there was no difference between GF and CV mice in histochemical and lectin-histochemical properties. In the cecal mucosa, DBA stained the goblet cells strongly in CV mice but not in GF mice and UEA-I stained the goblet cells strongly in the lower part of crypts in CV mice but only faintly in GF mice. These findings suggest that terminal residues of cecal goblet cell mucin were different in GF and CV mice. Morphometrically, cecal goblet cells were fewer in number and smaller in size in GF mice than in CV mice. In addition, high iron diamine-alcian blue staining made a very clear border between the cecum and colon, because cecal goblet cells were exclusively positive for sulfomucin and colonic goblet cells were predominantly positive for sialomucin.

No abstract

No abstract