Expression of tumor-associated antigens in acute myeloid leukemia: Implications for specific immunotherapeutic approaches

The expression of tumor-associated antigens (TAAs) might play a critical role in the control of minimal residual disease (MRD) in acute myeloid leukemia (AML), and therefore might be associated with clinical outcome in AML. In a DNA microarray analysis of 116 AML samples, we found a significant correlation between high mRNA levels of G250/CA9 and longer overall survival (P = .022), a similar trend with high mRNA levels of PRAME (P = .103), and a hint for RHAMM/HMMR. In contrast, for other TAAs like WT1, TERT, PRTN3, BCL2, and LAMR1, we found no correlation with clinical outcome. High expression of at least 1 of the 3 TAAs, RHAMM/HMMR, PRAME, or G250/CA9, provided the strongest favorable prognostic effect (P = .005). Specific T-cell responses were detected in 8 (47%) of 17 patients with AML in complete remission for RHAMM/HMMR-R3 peptide, in 7 (70%) of 10 for PRAME-P3 peptide, and in 6 (60%) of 10 for newly characterized G250/CA9-G2 peptide, a significant increased immune response compared with patients with AML patients who had refractory disease (P < .001). Furthermore, we could demonstrate specific lysis of T2 cells presenting these epitope peptides. In conclusion, expression of the TAAs RHAMM/HMMR, PRAME, and G250/CA9 can induce strong antileukemic immune responses, possibly enabling MRD control. Thus, these TAAs represent interesting targets for polyvalent immunotherapeutic approaches in AML.     

Evaluation of estrogenic activity from a municipal wastewater treatment plant with predominantly domestic input

The purpose of this study was to survey estrogenic releases from two primarily domestic wastewater treatment plants over three seasons (1996-1999). Mature male channel catfish were maintained at two sites within each WWTP and a reference site for 21 days. Estrogenic activity of effluent was assessed by the Yeast Estrogen Screen (YES) assay (in 1999) and the expression of the female egg yolk precursor protein, vitellogenin (Vtg) in caged male channel catfish (1996-1998). Serum Vtg of animals exposed at WWTP-A was induced 220% above reference values in the Fall of 1996 and 480% in Spring of 1997. In animals exposed to effluent of WWTP-B, serum Vtg was elevated 370% in Spring of 1997 and 480% in Fall of 1997 relative to fish held in a reference location. Serum 17-beta-estradiol (E2) levels were also significantly elevated 13 and 16-fold in the Fall 1997 and Summer 1998 in the fish exposed to WWTP-A effluent. A 13.5-fold increase in serum E2 was observed in fish exposed to WWTP-B during Fall 1997. Utilizing an E2 concentration-Vtg response curve generated in the laboratory, effluent from both plants (in 1997 and 1998) had estrogen equivalent values ranging from 23 to 123 ng/l E2 equivalents. These values were comparable with YES values obtained from 1999, which indicated the presence of 21 to 147 ng/l E2 equivalents. E2 was responsible for 3 (fall) to 100% (summer) of the YES activity. Glucuronides of E2 were also observed in the treated effluent. These studies indicate that variable estrogenic activity is present in municipal wastewater resulting from domestic activities and that this activity may be significantly altered by environmental factors.     

Comparison of cytogenetic and molecular cytogenetic detection of chromosome abnormalities in 240 consecutive adult patients with acute myeloid leukemia.

PURPOSE: To prospectively compare cytogenetic and molecular cytogenetic analysis for the detection of the most relevant chromosome abnormalities in a large series of patients with acute myeloid leukemia (AML). PATIENTS AND METHODS: Two hundred forty consecutive adult patients with AML entered onto the multicenter treatment trial AML HD93 were studied. Chromosome banding and fluorescence in situ hybridization (FISH) applying a comprehensive set of genomic DNA probes were performed in a single reference laboratory. RESULTS: Two cases of inv(16), three cases of t(11q23), and three cases of t(8;21)var were only detected by molecular cytogenetics. By FISH, aberrations were identified in three cases with normal karyotypes: inv(16), -Y (in a patient with low metaphase yield on chromosome banding) and a 12p microdeletion. Additional aneuploidies, in particular +8q and +11q, were diagnosed by FISH; however, virtually all these aberrations occurred in patients with complex karyotypes or as an additional abnormality in leukemias with an AML-specific translocation. Finally, aberrations were detected by FISH in eight of 14 patients with no assessable metaphases. CONCLUSION: In most cases of AML, conventional cytogenetic study reliably detects chromosomal abnormalities, and this method should not be replaced by FISH. FISH should be used as a complementary method for the detection of more subtle abnormalities, such as inv(16) and t(11q23), in all patients with newly diagnosed AML and for suspected t(8;21)var. Furthermore, molecular cytogenetics using this comprehensive set of DNA probes provides a valuable diagnostic tool for patients with poor chromosome morphology, low or no yields of metaphase cells, or both.     

Vertical transmission of Kaposi's sarcoma

AIDS related Kaposi's sarcoma is commonly seen in homosexual men, only occasionally in men and women with heterosexually acquired HIV, and extremely rarely in children. The case of an HIV infected mother and her vertically infected child who both developed visceral Kaposi's sarcoma is reported. It is proposed that the putative Kaposi's sarcoma agent may also be transmitted vertically.     

Evaluation of wetland and tertiary wastewater treatments for estrogenicity using in vivo and in vitro assays

The effects of wetland wastewater treatment on estrogenic activity and estrogenic activity of water after tertiary treatment were evaluated using in vivo (rainbow trout vitellogenin [VTG] expression) and in vitro (yeast estrogen screening) assays. Juvenile rainbow trout exposed to tertiary-treated wastewater from the Green Acres Treatment Plant in Orange County Water District had increased plasma VTG levels compared with control fish. When trout were exposed to wastewater-dominated water before it entered into Prado Wetland (Riverside County, CA), VTG concentrations were increased above those of controls and were not significantly different from fish exposed to water exiting the wetland. VTG E2-equivalent concentrations (EEQs) of the water samples from the Green Acres Plant were 16.92 +/- 16.49 ng/L. Activity of water entering Prado Wetland was 29.80 +/- 28.41 ng/L EEQ, and water exiting was 24.34 +/- 23.17 ng/L EEQ. In vitro assays estimated that estrogenic activity of water from the Green Acres Plant was <1 ng/L EEQ, whereas water entering and exiting Prado Wetland had yeast estrogen screening EEQs of 2.57 and <1 ng/L, respectively. Our results suggest that environmental estrogens that are not potent estrogen-receptor ligands exist in wastewaters from the Green Acres Plant as well as water entering and exiting Prado Wetland. Wetland treatment did not remove environmental estrogens in the water. Our results also suggest that in vitro assays may underestimate estrogenic activity of sampled water.     

Medication non-adherence among older adults: a review of strategies and interventions for improvement

Medication non-adherence among older adults is a prevalent and costly problem; approximately one half have problems following their prescribed medication regimen, and more than 10% of hospital admissions are the result of medication non-adherence. In this literature review, medication non-adherence is defined and described among adults age 50 and older. Factors associated with medication non-adherence are presented, interventions to improve medication non-adherence are discussed, and methods for assessing medication non-adherence are reviewed. In addition, nursing assessment and intervention to improve medication non-adherence are described.