Microsatellite instability in gynecological sarcomas and in hMSH2 mutant uterine sarcoma cell lines defective in mismatch repair activity

We have examined a panel of gynecological sarcomas for microsatellite instability. The genomic DNA from 11 of 44 sarcomas contained somatic alterations in the lengths of one or more di-, tri-, tetra-, or pentanucleotide microsatellite sequence markers, and 6 of these cases had alterations in two or more markers. In addition, di-, tri-, and tetranucleotide microsatellites were found to be highly unstable in single cell clones of two cell lines derived from a uterine mixed mesodermal tumor. Since such instability is characteristic of cells defective in postreplication mismatch repair, we examined mismatch repair activity in extracts made from these lines. Both extracts were repair deficient, while an extract of another gynecological sarcoma cell line not exhibiting microsatellite instability was repair proficient. The repair deficiency was complemented by a colon tumor cell extract that was defective in the hMLH1 protein but not by an extract defective in hMSH2 protein. This suggested that the defect in the uterine sarcoma line could be in hMSH2. Subsequent analysis of the gene revealed a 2-bp deletion in exon 14, leading to premature truncation of the hMSH2 protein at codon 796 and no detectable wild-type gene present. These data suggest that the microsatellite instability observed in these cell lines, and possibly in a significant number of gynecological sarcomas, is due to defective postreplication mismatch repair. There was no apparent correlation with microsatellite instability and clinical outcome.     

Spatial organization of electrical processes in the brain: problems and solutions

Theoretical questions of the spatial organization of electrical activity in the brain are discussed in terms of a multilevel realization of the synergetic principle for formation of functional systems underlying behavior and mental function. The role of the spatial-temporal superimposition of coherent structures of biopotentials in generating fields of increased activity in the cerebral cortex is discussed, these being responsible for integrative and associative functions. A hypothesis is proposed regarding the relationship between the energy and information factors of coherent structures as one of the important characteristics describing the efficiency of energy-informational processes. Emphasis is placed on the need for considering not only linear, but also nonlinear associations of biopotentials in considerations of the form and functional sense of their spatial organization.     

Adenoid cystic carcinoma of the submandibular gland with symptomatic ovarian metastases

We report the clinical and pathologic features of an adenoid cystic carcinoma of the submandibular gland that metastasized to the ovaries 10 years after initial presentation. A 30-year-old woman underwent excision of a right submandibular adenoid cystic carcinoma followed by regional external beam radiation therapy. Three years later, she underwent extended hepatic resection and localized radiotherapy to the hepatic region for metastatic disease. The patient was without evidence of disease for 7 years when she developed pelvic pain and a pelvic mass was found. A solid and cystic 10-cm left ovarian mass and a single metastatic tumor nodule involving the right ovary were excised via the laparoscope. Histologically, the tumor was identical to the patient's initial salivary gland neoplasm. The neoplastic cells were CAM 5.2 positive, S100 positive, muscle-specific actin positive, and smooth muscle actin positive. Ultrastructurally, characteristic pseudocysts (pseudolumina) with abundant basal lamina and true glandular lumina lined by short microvilli were present. Other than a single anecdotal account of a parotid gland adenoid cystic carcinoma, this case represents the first documented report of an adenoid cystic carcinoma of salivary gland origin that was associated with symptomatic ovarian metastases. This case demonstrates that the ovary is a potential site for metastatic disease many years following the diagnosis and treatment for a primary neoplasm however uncommon or remote the site of origin. Since metastatic adenoid cystic carcinoma can rarely present as an ovarian mass, a clinical history of this neoplasm should be heavily weighed in the differential diagnosis of any unusual ovarian tumor with a predominant cribriform, trabecular, or tubular pattern.     

Suprasellar osteolipoma: case report

BACKGROUND: Osteolipomas are distinguished from other intracranial lipomas by their arrangement of central adipose and peripheral osseous tissues and by characteristically arising in the suprasellar/interpeduncular region. METHODS: We report computed tomography (CT), magnetic resonance imaging (MRI), and pathology findings from this 34-year-old man who underwent surgical removal of this benign lesion. RESULTS: This case displays the distinctive histopathology that has been reported in 13 of 31 (42%) lipomas in this region. In contrast, ossification of lipomas at other intracranial sites is relatively rare. CONCLUSIONS: Ossification should be expected in many suprasellar/interpeduncular lipomas, and osteolipoma should be included in the radiologic differential diagnosis of fat-intensity masses with calcification in this region.     

Comparative pharmacodynamics of CYP2B induction by DDT, DDE, and DDD in male rat liver and cultured rat hepatocytes

In this study the pharmacodynamics were characterized of rat hepatic cytochrome P-450 2B (CYP2B) induction by the pesticide DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane] and its metabolites DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene], which is bioretained, and DDD [1,1-dichloro-2,2-bis(p-chlorophenyl)ethane], which is metabolized further and therefore less prone to bioaccumulate. DDT, DDE, and DDD were each found to be pure phenobarbital-type cytochrome P-450 inducers in the male F344/NCr rat, causing induction of hepatic CYP2B and CYP3A, but not CYP1A. The ED50 values for CYP2B induction (benzyloxyresorufin O-dealkylation) by DDT, DDE, and DDD were, respectively, 103, 88, and > or = 620 ppm in diet (14 d of exposure). The efficacies (Emax values) for induction of benzyloxyresorufin O-dealkylation by DDT, DDE, and DDD were 24-, 22-, and > or = 1-fold, respectively, compared to control values. The potencies of the three congeners for CYP2B induction appeared also to be similar, with EC50 values (based on total serum DDT equivalents) of 1.5, 1.8, and > or = 0.51 microM, respectively. The EC50 values based on DDT equivalents in hepatic tissue were 15, 16, and > or = 5.9 micromol/kg liver tissue, respectively. In primary cultures of adult rat hepatocytes, DDT, DDE, and DDD each displayed ability to induce total cellular RNA coding for CYP2B (ED50 values of 0.98, 0.83, and > or = 2.7 microM, respectively). These results suggest that DDT, DDE, and DDD each possess a high degree of intrinsic CYP2B-inducing ability for rat liver, despite marked differences in bioretention among the congeners.