Obacunone and limonin are bitter limonoids in citrus. Their modifying effects on the development of aberrant crypt foci (ACF), the activity of detoxification enzymes, glutathione S-transferase (GST) and quinone reductase (QR), and cell proliferation activity were investigated in male F344 rats treated with azoxymethane (AOM). Obacunone and limonin were administered in the diet, during the initiation (for 4 weeks) or postinitiation phase (for 4 weeks) of AOM-induced tumorigenesis. Feeding of obacunone and limonin (0.02% or 0.05%) caused significant reduction (55-65% by "initiation" feeding and 28-42% by "postinitiation" feeding) in the yield of ACF. The ability to reduce the proliferating cell nuclear antigen-labeling index in crypts and correlated well with the prevention of ACF. In a subsequent long-term experiment (38 weeks), in which rats were initiated with AOM and fed 0.05% obacunone or 0.05% limonin during the initiation or post-initiation phase, both compounds in diet caused significant reduction (65%-92% inhibition) in the incidence of colonic adenocarcinoma. Thus, citrus bitter limonoids obacunone and limonin possess chemopreventive effects on chemically induced rat colon carcinogenesis.

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Keywords: apoptosis/high polyploid/tumor ABSTRACT. It is well known that DNA-ploidy is useful independent prognosticator of malignancy. However, the biological significance of polyploid cells and the relation between polyploidy and prognosis is not well understood. We analyzed DNAploidy by flow cytometry in Meth-A cells (a cultured sarcoma cell line) after treatment with K252a, a protein kinase inhibitor, and showed induction of polyploidization.Apoptotic cell death of the high polyploid cells was verified by flow cytometry, morphological observation and gel analysis of DNAintegrity. Expression of tumor-suppressor nuclear protein p53 investigated by immunohistochemistry was increased 10-fold or more in cells with 16C (C=haploid DNAcontent) relative to cells with 2C, suggesting that the overexpression of p53 was involved in the apoptosis. These results may be of clinical relevance since it has been known that both DNAploidy and p53 expression have prognostic significance.

A 68‐year‐old woman complained of repeated signs of congestive heart failure during the last 10 years. Clinical examination revealed persistent marked eosinophilia of the peripheral blood. Postmortem examination of the heart revealed multiple thrombo‐embolic materials of the small vascular lumina throughout the myocardium, associated with marked perivascular and stromal infiltration of eosinophils, many foci of myocardial necrosis, and diffuse myocardial fibrosis. There was also an organizing thrombus in the posterior mitral valve. Neither subendocardial fibrosis, overlying mural thrombi in the endocardium, pulmonary infiltration of eosinophils nor systemic granulomatous or healed vasculitis in the lungs and other organs were found. The disease is preferably consistent with a diagnosis of hypereosinophilic syndrome of Hardy et al., a group of ill‐defined and overlapping conditions, and best descriptively termed as eosinophilic interstitial myocarditis.