Loss of heterozygosity mutations of tumor suppressor genes in cytologically atypical areas in chronic lymphocytic thyroiditis

The relationship between chronic lymphocytic thyroiditis (CLT) and papillary thyroid carcinoma (PTC) is a subject of controversy. Some investigators suggest a causal relationship, whereas others regard the two as only a coincidental occurrence. An additional complicating factor is the presence of atypical nuclei frequently found within lymphoid infiltrates in CLT, which resemble those in PTC. The finding of the RET-PTC translocations in CLT has been reported by two independent groups of investigators, suggesting that the areas of nuclear atypia in CLT are neoplastic rather than reactive. In the present study, we report additional molecular findings that support the hypothesis that the atypical nuclear changes in CLT may be preneoplastic or neoplastic. We microdissected small areas with atypical nuclei in glands with CLT and observed loss-of-heterozygosity mutations of tumor suppressor genes. These genetic mutations are evidence of clonal preneoplastic or neoplastic changes in the follicular cells of CLT. The clinical malignant potential of these minute foci is likely to be very small but remains to be determined.     

Molecular alterations in atypical adenomatous hyperplasia occurring in benign and cancer-bearing lungs.

Atypical adenomatous hyperplasia (AAH) is considered to be a precursor lesion of the lung adenocarcinoma. Several genetic abnormalities have been reported in AAH associated with adenocarcinoma, but little is known about AAH associated with benign lung lesions. To address this we compared the molecular characteristics of AAH present in benign conditions to those coexisting with carcinoma. Seven cases of AAH from resected non-neoplastic lungs (AAH-B) and 12 cases from lungs resected for primary lung carcinoma (AAH-M) were analyzed for loss of heterozygosity (LOH) using 21 polymorphic microsatellite markers situated in proximity to known tumor suppressor genes on chromosomes 3p, 5q, 7p, 9p, 10q, and 17p. Direct DNA sequencing for K-ras mutation was also performed. There was a broad range of LOH in both groups. No LOH was identified in 3 cases (25%) of AAH-M, but all cases of AAH-B showed LOH (P=0.26). Six cases (50%) of AAH-M and 3 cases (43%) of AAH-B showed loss at 1 marker (P=0.99). LOH at 2 or more markers was identified in 3 (25%) cases of AAH-M and 4 (57%) cases of AAH-B (P=0.32). LOH was most frequently detected on chromosomes 3p and 10q in both groups. The difference in overall fractional allelic loss between the 2 groups did not reach statistical significance. K-ras mutations were not identified in either group. Our results showed a significant overlap in LOH patterns between AAH with or without coexistent lung malignancy. Therefore, AAH may represent a smoking induced low-grade neoplastic lesion that may be a precursor lesion of only a subset of invasive lung adenocarcinoma.     

Clonal Diversity and Turnover of Streptococcus mitis bv. 1 on Shedding and Nonshedding Oral Surfaces of Human Infants during the First Year of Life

Streptococcus mitis bv. 1 is a pioneer colonizer of the human oral cavity. Studies of its population dynamics within parents and their infants and within neonates have shown extensive diversity within and between subjects. We examined the genetic diversity and clonal turnover of S. mitis bv. 1 isolated from the cheeks, tongue, and primary incisors of four infants from birth to 1 year of age. In addition, we compared the clonotypes of S. mitis bv. 1 isolated from their mothers' saliva collected in parallel to determine whether the mother was the origin of the clones colonizing her infant. Of 859 isolates obtained from the infants, 568 were unique clones. Each of the surfaces examined, whether shedding or nonshedding, displayed the same degree of diversity. Among the four infants it was rare to detect the same clone colonizing more than one surface at a given visit. There was little evidence for persistence of clones, but when clones were isolated on multiple visits they were not always found on the same surface. A similar degree of clonal diversity of S. mitis bv. 1 was observed in the mothers' saliva as in their infants' mouths. Clones common to both infant and mothers' saliva were found infrequently suggesting that this is not the origin of the infants' clones. It is unclear whether mucosal immunity exerts the environmental pressure driving the genetic diversity and clonal turnover of S. mitis bv. 1, which may be mechanisms employed by this bacterium to evade immune elimination.     

United we stand? The effects of a couple-coping intervention on adjustment to early stage breast or gynecological cancer

Cancer diagnosis affects the psychological well-being of both patients and their partners, and effective coping has been suggested to be a conjoint process of mutual support. Ninety-four married women with early stage cancer and their partners were randomly assigned to couples-based coping training (CanCOPE), individual coping training for the woman, or a medical education control. Couples' observed support communication and self-reported psychological distress, coping effort, and sexual adjustment were assessed at diagnosis, after cancer surgery, and at 6- and 12-month follow-ups. CanCOPE produced significant improvements in couples' supportive communication, reduced psychological distress and coping effort, and improved sexual adjustment. Training in couples rather than individual coping was more effective in facilitating adaptation to cancer.     

Nano-C60 cytotoxicity is due to lipid peroxidation

This study examines the biological effects of water-soluble fullerene aggregates in an effort to evaluate the fundamental mechanisms that contribute to the cytotoxicity of a classic engineered nanomaterial. For this work we used a water-soluble fullerene species, nano-C₆₀, a fullerene aggregate that readily forms when pristine C₆₀ is added to water. Nano-C₆₀ was cytotoxic to human dermal fibroblasts, human liver carcinoma cells (HepG2), and neuronal human astrocytes at doses 50 ppb (LC₅₀=2–50 ppb, depending on cell type) after 48 h exposure. This water-soluble nano-C₆₀ colloidal suspension disrupts normal cellular function through lipid peroxidation; reactive oxygen species are responsible for the membrane damage. Cellular viability was determined through live/dead staining and LDH release. DNA concentration and mitochondrial activity were not affected by the nano-C₆₀ inoculations to cells in culture. The integrity of cellular membrane was examined by monitoring the peroxy-radicals on the lipid bilayer. Subsequently, glutathione production was measured to assess the cell's reaction to membrane oxidation. The damage to cell membranes was observed both with chemical assays, and confirmed physically by visualizing membrane permeability with high molecular weight dyes. With the addition of an antioxidant, l-ascorbic acid, the oxidative damage and resultant toxicity of nano-C₆₀ was completely prevented.     

Risk and protective factors for suicidal behavior in abused African American women

This study examined risk and protective factors that differentiate low-income, abused African American women (N = 200) who attempted suicide from those who had never made a suicide attempt. Results from multivariate analyses revealed that numerous and/or severe negative life events, a history of child maltreatment, high levels of psychological distress and depression, hopelessness about the future, and alcohol and drug problems were factors associated with attempter status. Protective factors associated with nonattempter status included hopefulness, self-efficacy, coping skills, social support, and effectiveness in obtaining material resources. Culturally competent intervention approaches for abused women should target increasing their protective factors and reducing their risk factors to decrease the likelihood that these women engage in suicidal behavior.