Significance of Strain and Sex Differences in the Development of 252Cf Neutron-induced Liver Tumors in Mice

Mouse liver tumors occurring in C3H/HeN, C57BL/6N and C3B6F1 hybrid (C3H × C57BL) were studied following ²⁵²Cf fission neutron irradiation. Three strains of mice of both sexes (about 30 mice/group) were irradiated once with ²⁵²Cf at doses of 0,12.5, 50 and 200 cGy. The groups were observed for 13 months after irradiation. The incidence of liver tumors in the non-irradiated controls was 0% in both sexes of CS7BL/6N, 11.7% in males and 0% in females of C3B6F1 and 39.5% in males and 11.4% in females of C3H/HeN mice. In the four strains of mice thus far studied, including B6C3F1 hybrid (CS7BL × C3H) which was previously studied, ²⁵²Cf irradiation has increased the tumor incidence dose-dependently in males and in females, but less effectively in females. The mean number and size of liver tumors were clearly correlated with tumor incidence. The incidence was always highest in C3H/HeN mice of both sexes, followed by B6C3F1, C3B6F1 and C57BL/6N mice. The influence of sex hormones was studied in B6C3F1 mice of both sexes after 200 cGy of ²⁵²Cf irradiation. In males, the incidence of liver tumors was significantly decreased from 55.2% to 23.3% and 25.9% after orchidectomy, and in females it was slightly decreased from 27.6% to 14.8% and 18.8% after ovariectomy. Supplementation of testosterone in orchidectomized mice did not restore the occurrence of liver tumors.     

Rationale and design for a study using intravascular ultrasound to evaluate effects of rosuvastatin on coronary artery atheroma in Japanese subjects: COSMOS study (Coronary Atherosclerosis Study Measuring Effects of Rosuvastatin Using Intravascular Ultrasound in Japanese Subjects).

BACKGROUND: There have been few multicenter studies using intravascular ultrasound (IVUS) to assess the process of atherosclerosis in a Japanese population with hypercholesterolemia that is being treated with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors for control of low-density lipoprotein-cholesterol. METHODS AND RESULTS: An open-label multicenter study is planned to evaluate with IVUS whether treatment with rosuvastatin for 76 weeks results in regression of coronary artery atheroma volume in patients who have coronary heart disease (CHD) and hypercholesterolemia. Sample size is 200 subjects with CHD who are to undergo percutaneous coronary intervention. The planned duration is between October 2005 and October 2008. CONCLUSIONS: The COSMOS study will be the first multicenter cardiovascular study in a Japanese population and may provide new evidence on the effects of rosuvastatin on the progression of coronary atherosclerotic lesions.     

Effects of sex hormones on induction of intestinal metaplasia by X-irradiation in rats.

The influence of sex hormones on induction of intestinal rnetaplasia was examined in 5 week old Crj: CD (SD) rats of both sexes. At the age of 4 weeks, the animals were gonadectornized and given testosterone or dimethyl estradiol (DES). One week after operation, they were irradiated with two 10 Gy doses of X-rays to the gastric region at a 3 day interval for a total of 20 Gy. At the termination of the experiment, 6 months after the X-irradiation, the incidence of intestinal metaplasia with alkaline phosphatase (ALP) positive foci in males was significantly higher than in females, in orchidectomized males or orchidectomized plus DES treated rats (P <0.01). On the other hand, the incidence of intestinal metaplasia with ALPpositive foci in normal females appeared lower than in ovariectomized females (P < 0.01), and was increased in rats by treatment with testosterone or decreased by DES. Numbers of foci of intestinal metaplasias with Paneth cells and total numbers appeared to increase in males treated with DES. The results suggested a promoting role for testosterone in the development of ALP positive lesions and indicated considerable heterogeneity between intestinal metaplasia subtypes.     

Different characteristics of cardiac biomarkers to decide and predict the culprit lesions in patients with suspicious acute coronary syndrome

This multicenter prospective study was conducted to assess high-sensitivity troponin T (hs-TnT) and other biomarkers to decide and predict culprit lesions indicated for emergency percutaneous coronary intervention (PCI) in patients with suspicious acute coronary syndrome (ACS). We have reported Hs-TnT is the most sensitive biomarker for earlier diagnosis and decision making in patients with suspected ACS. In this study, we had conducted subanalysis investigating the usefulness for prediction of ACS culprit lesion. The patients with suspicious ACS and initially negative whole-blood rapid troponin T test, who underwent coronary angiogram (CAG), were enrolled (n = 74). Hs-TnT, quantitative assay for conventional troponin T (c-TnT), creatine kinase MB isozyme (CK-MB), and heart-type fatty acid-binding protein (H-FABP) were simultaneously measured. ACS culprit lesion was described as total occlusion, subtotal occlusion, and/or angiographical unstable lesion such as thrombosis, ulceration or irregularity. The CAG revealed that 49 cases had ACS lesions to be indicated for emergency PCI. The areas under the ROC curves and ROC-optimized cut-off of hs-TnT, c-TnT, CK-MB, and H-FABP were 0.75, 0.67, 0.68, and 0.75, respectively, and 18, 11, 2.0, and 4.6 ng/ml, respectively. In patients with total occlusion and 90–99 % of diameter stenosis (TIMI 2 or 3), hs-TnT could predict emergency PCI with significantly higher sensitivity compared with H-FABP (hs-TnT >14 ng/ml; 71 %, and H-FABP >6.2 ng/dl; 51 %, p = 0.021) and other biomarkers. Meanwhile, H-FABP displayed significant correlations with number of diseased vessels and presence of thrombotic lesion. The present study first revealed different characteristics of correlation between the angiographic culprit lesions and each cardiac biomarker. For prediction of ACS lesions requiring emergency PCI, hs-TnT had the highest sensitivity with satisfied analytical precision.     

Xanthomatous meningioma: a case report with review of the literature

Xanthomatous meningioma is an extremely rare variant of meningioma that is characterized histopathologically by the presence of tumor cells with lipid-filled vacuolated cytoplasm. In this report, we describe the fifth documented case of xanthomatous meningioma and review its clinicopathological features. A 76-year-old Japanese male presented with dizziness. Magnetic resonance imaging demonstrated a well-circumscribed tumor in the left parasagittal to frontal region with attachment of the dura mater. Histopathological examination of the resected specimen revealed proliferation of polygonal to spindle cells with eosinophilic cytoplasm and bland round to oval nuclei. Whorl formation and psammomas were scattered, and mitotic figures were rarely seen. A peculiar finding was the presence of extensive xanthomatous change continuing to the above-mentioned typical meningothelial meningioma. These tumor cells had clear vacuolated cytoplasm and bland round to oval nuclei. Immunohistochemically, xanthomatous cells were positive for epithelial membrane antigen. Accordingly, an ultimate diagnosis of xanthomatous meningioma was made. Our clinicopathological analysis revealed that xanthomatous meningioma affects children to young persons or the elderly, and four of five cases were located in the supratentorial region. Although the detailed mechanism underlying the xanthomatous change has not been clarified, this change is thought to result from a metabolic abnormality of the neoplastic meningothelial cells. Further, xanthomatous change has also been reported in atypical and anaplastic meningiomas. Therefore, it is important to recognize that xanthomatous change can occur in meningiomas, and to avoid misidentifying these cells as macrophages.     

Influence of Paternal 252Cf Neutron Exposure on Abnormal Sperm, Embryonal Lethality, and Liver Tumorigenesis in the F1 Offspring of Mice

Experiments were conducted to determine whether neutron-induced genetic damage in parental germline cells can lead to the development of cancer in the offspring. Seven-week-old C3H male mice were irradiated with ²⁵²Cf neutrons at a dose of 0, 50, 100, or 200 cGy. Two weeks or 3 months after irradiation, the male mice were mated with virgin 9-week-old C57BL females. Two weeks after irradiation, the irradiated male mice showed an increased incidence of sperm abnormalities, which led to embryo lethalities in a dose-dependent manner when they were mated with unirradiated female mice. Furthermore, liver tumors in male offspring of male mice in the 50 cGy group were significantly increased in 19 of 44 (43.2%) animals, in clear contrast to the unirradiated group (1 of 31; 3.2%) ( P < 0.01). In the 100 cGy group, 6 of 39 (15%) mice had lesions. At 3 months after irradiation abnormal sperm and embryonal lethality were not significantly increased. The incidences of liver tumors in male offspring from the 50 cGy, 100 cGy and 200 cGy groups were 6 of 20 (30%), 5 of 22 (23%) and 1 of 19 (5%), respectively, which are not significantly increased compared with the control. It is concluded that increased hepatic tumor risk in the F₁ generation may be caused by genetic transmission of hepatoma-associated trait(s) induced by ²⁵²Cf neutron irradiation.     

Deep extension from carcinoma arising from the gingiva: CT and MR imaging features

BACKGROUND AND PURPOSE: CT and MR imaging are useful for evaluating the extension of carcinomas in the face and neck. We evaluated the involvement by carcinoma arising from the gingiva (ie, gingival cancer) by using CT and MR imaging. METHODS: We retrospectively examined 122 patients with squamous cell carcinoma (SCCA) in the lower (88 patients) and upper (34 patients) gingiva. Extension of SCCA into the spaces of the face and neck was evaluated with CT and MR imaging, and findings were surgically confirmed. RESULTS: Spread into the face and neck spaces occurred in 58% of patients. The buccal space was the most common site of spread, occurring in 42% of the lower and of 47% of the upper gingival cancers. Spread into the masticator space occurred from the lower gingival cancers in the molar region (20%) but not from the anterior region. Masticator space involvement from the upper gingiva was rare (4%). The retromolar triangle and buccal space immediately anterior to the ramus served as a corridor for cancer extension from the lower gingiva into the masticator space. The sublingual space (11%) was a less common site of spread from the lower gingiva. CONCLUSION: Gingival cancers spread into the masticator, buccal, and sublingual spaces depending on the primary sites in the oral cavity. An understanding of the face and neck-space anatomy is important in diagnosing cancer extension in the oral cavity gingiva and in treating patients with such disease.