Citations

Abstract T cells respond to external signals by altering patterns of gene expression. Our characterization of a transgenic mouse revealed a genetic locus that is specifically regulated in T cells. Elucidation of the factors controlling the expression of the marker transgene may reveal basic regulatory mechanisms used by T cells as they differentiate from naive to primed/memory T cells. Although endogenous MHC class I Kq expression is normal in these animals, expression of the Kb transgene differentiates naive from primed/memory T cells. KbHigh T cells bear the phenotypic and functional properties of primed/memory T cells, while KbLow T cells have naive phenotypes. The transition from KbLow to KbHigh appears to involve signals resulting from engagement of the TCR. We show that transgene integration has occurred on chromosome 1, between D1Mit365 and D1Mit191. The gene regulatory mechanisms directing expression of the locus marked by the transgene are distinct from those controlling other known T cell-related genes within this locus. Stimulation of KbHigh T cells results in the up-regulation of both the endogenous Kq gene and the Kb transgene. However, the same stimuli induce increased expression of only Kq on KbLow T cells. This indicates that even though the transcription factors necessary for class I expression are present in KbLow T cells, the Kb gene appears not to be accessible to these factors. These findings suggest a change in chromatin structure at the transgene integration site as cells progress from a naive to a primed/memory differentiation state.

We report the finding of Iodamoeba butschlii amebic cysts on a liquid‐based anal Pap smear from an HIV‐positive male. Iodine staining of the smear confirmed the diagnosis. It is important to distinguish I. butschlii from pathogenic ameobae and other organisms seen on anal Pap smears. Diagn. Cytopathol 2014;42:775–777. © 2013 Wiley Periodicals, Inc.

Background: As defined by the Dietary Supplement Health and Education Act 1997, such substances as herbs and dietary supplements fall under general Food and Drug Administration supervision but have not been closely regulated to date. We examined the thyroid hormone content in readily available dietary health supplements marketed for “thyroid support.” Methods: Ten commercially available thyroid dietary supplements were purchased. Thyroid supplements were dissolved in 10 mL of acetonitrile and water with 0.1% trifloroacetic acid and analyzed using high-performance liquid chromatography for the presence of both thyroxine (T4) and triiodothyronine (T3) using levothyroxine and liothyronine as a positive controls and standards. Results: The amount of T4 and T3 was measured separately for each supplement sample. Nine out of 10 supplements revealed a detectable amount of T3 (1.3–25.4 μg/tablet) and 5 of 10 contained T4 (5.77–22.9 μg/tablet). Taken at the recommended dose, 5 supplements delivered T3 quantities of greater than 10 μg/day, and 4 delivered T4 quantities ranging from 8.57 to 91.6 μg/day. Conclusions: The majority of dietary thyroid supplements studied contained clinically relevant amounts of T4 and T3, some of which exceeded common treatment doses for hypothyroidism. These amounts of thyroid hormone, found in easily accessible dietary supplements, potentially expose patients to the risk of alterations in thyroid levels even to the point of developing iatrogenic thyrotoxicosis. The current study results emphasize the importance of patient and provider education regarding the use of dietary supplements and highlight the need for greater regulation of these products, which hold potential danger to public health.

Abstract A drug-induced apoptosis assay, termed the microculture-kinetic (MiCK) assay, has been developed. Blinded clinical trials have shown higher response rates and longer survival in groups of patients with acute myelocytic leukemia and epithelial ovarian cancer who have been treated with drugs that show high apoptosis in the MiCK assay. Unblinded clinical trials in multiple tumor types have shown that the assay will be used frequently by clinicians to determine treatment, and when used, results in higher response rates, longer times to relapse, and longer survivals. Model economic analyses suggest possible cost savings in clinical use based on increased generic drug use and single-agent substitution for combination therapies. Two initial studies with drugs in development are promising. The assay may help reduce costs and speed time to drug approval. Correlative studies with molecular biomarkers are planned. This assay may have a role both in personalized clinical therapy and in more efficient drug development. Cancer Res; 72(16); 3901–5. ©2012 AACR.

Purpose In lung cancer, randomized trials assessing hyperfractionated or accelerated radiotherapy seem to yield conflicting results regarding the effects on overall (OS) or progression-free survival (PFS). The Meta-Analysis of Radiotherapy in Lung Cancer Collaborative Group decided to address the role of modified radiotherapy fractionation. Material and Methods We performed an individual patient data meta-analysis in patients with nonmetastatic lung cancer, which included trials comparing modified radiotherapy with conventional radiotherapy. Results In non–small-cell lung cancer (NSCLC; 10 trials, 2,000 patients), modified fractionation improved OS as compared with conventional schedules (hazard ratio [HR] = 0.88, 95% CI, 0.80 to 0.97; P = .009), resulting in an absolute benefit of 2.5% (8.3% to 10.8%) at 5 years. No evidence of heterogeneity between trials was found. There was no evidence of a benefit on PFS (HR = 0.94; 95% CI, 0.86 to 1.03; P = .19). Modified radiotherapy reduced deaths resulting from lung cancer (HR = 0.89; 95% CI, 0.81 to 0.98; P = .02), and there was a nonsignificant reduction of non–lung cancer deaths (HR = 0.87; 95% CI, 0.66 to 1.15; P = .33). In small-cell lung cancer (SCLC; two trials, 685 patients), similar results were found: OS, HR = 0.87, 95% CI, 0.74 to 1.02, P = .08; PFS, HR = 0.88, 95% CI, 0.75 to 1.03, P = .11. In both NSCLC and SCLC, the use of modified radiotherapy increased the risk of acute esophageal toxicity (odds ratio [OR] = 2.44 in NSCLC and OR = 2.41 in SCLC; P < .001) but did not have an impact on the risk of other acute toxicities. Conclusion Patients with nonmetastatic NSCLC derived a significant OS benefit from accelerated or hyperfractionated radiotherapy; a similar but nonsignificant trend was observed for SCLC. As expected, there was increased acute esophageal toxicity.