CTLA-4-Tg/CD-28-KO Mice Exhibit Reduced T Cell Proliferation in vivo Compared to CD-28-KO Mice in a Graft-versus-host Disease Model

Activated T cells express inhibitory receptors such as CTLA-4 that can downregulate immune responses. Blockade of or genetic deficiency in CTLA-4 can result in autoimmunity. Therefore, strategies to increase the inhibitory function of CTLA-4 may be attractive in settings of undesirable T cell responses such as autoimmunity or transplant rejection. We have tested the hypothesis that transgenic constitutive expression of CTLA-4 can further attenuate immune responses when compared with normal inducible expression. Our results indicate that transgenic expression of CTLA-4 in mouse T cells (CTLA-4-Tg T cells) results in reduced cell cycle progression and increased apoptosis of TCR-stimulated T cells. CTLA-4-Tg T cells display reduced T cell proliferation in an in vivo model of graft versus host disease (GVHD). These results further our understanding of how CTLA-4 can be manipulated to inhibit immune responses and may help development of new therapeutic strategies for clinical settings of autoimmunity and transplantation.     

Removal of Cyanobacteria and Microcystin by Natural Plant-Mineral Combinations in Eutrophic Waters

The removal or mitigation of cyanobacterial bloom and cyanotoxins is a necessity to ensure safe drinking water and recreational water. As a feasible agent to control cyanobacterial bloom, a novel plant-mineral composite (PMC) was developed and optimized through laboratory and field testing over the past 3 years. Based on previous studies, we treated cyanobacterial bloom water (mainly Microcystis and Synechocystis) with 0.05 mg/L PMC at the small eutrophic reservoir; 2 h later, we collected samples and analyzed them in the laboratory. The intra-cellular (c-MC) and dissolved microcystin-LR (d-MC) were measured using an ELISA method. The PMC exhibited a remarkable removal of both c-MC (47.3 %) and d-MC (95.8 %) within 2 days. In addition, notable decreases (on average, 78 % of the control) in the chlorophyll-a, suspended solids, total phosphorus and biochemical oxygen demand values, in zooplankton and in the phytoplankton density (83.9 %) were verified after 48 h. These results indicate that the PMC is more effective in controlling d-MC than c-MC, suggesting a possible method to mitigate such hazardous chemicals as agrochemicals and endocrine disrupters in aquatic ecosystems.     

“Symptom-Specific or Holistic”: Menopausal Symptom Management

Our purpose in this study was to identify differences in menopausal symptom management among four major ethnic groups in the United States. This was a secondary analysis of the qualitative data from a larger Internet-based study. We analyzed data from 90 middle-aged women in the United States using thematic analysis. We extracted four themes during the data analysis process: (a) “seeking formal or informal advice,” (b) “medication as the first or final choice,” (c) “symptom-specific or holistic,” and (d) “avoiding or pursuing specific foods.” Health care providers need to develop menopausal symptom management programs while considering ethnic differences in menopausal symptom management.     

Suspended Onion Particles and Potential Corneal Injury in Onion Harvesters

The authors suspected that suspended onion particles contributed to corneal ulcers in onion harvesters in southern Taiwan. In the present study, the authors used manikins to study suspended onion particles in fields in an effort to simulate typical conditions experienced by onion harvesters. An animal eye-exposure simulation study was also performed by the authors, who impacted suspended soil grains or onion particles onto the corneas of guinea pigs via aerosol generated from the Palas® dispersion nozzle. The average size of 25.9 μm for suspended particles collected during the digging of onions was the largest one of those for various harvesting activities. Some onion skin flakes were found in samples obtained from gathering and packing activities; the typical flake size was approximately 3.5 × 2.5 mm². The results of the animal study indicated that the size of soil grains has a demonstrable effect on the severity of corneal injury (p = .009). With respect to onion skin flakes, wind velocity was also associated significantly with the occurrence of corneal injury (p = .0004). A wind velocity threshold of 7 m/sec is recommended for the maintenance of safety, and if the wind speed exceeds this threshold level, workers should not engage in harvesting activities. Furthermore, use of appropriately designed goggles is necessary for the protection of onion harvesters who work in high-wind conditions.     

Paraquat Intoxication in Korea

In this study, the authors explored acute paraquat intoxication and determined potential factors related to paraquat fatalities. During 1999, 154 patients with paraquat intoxication were admitted to the Institute of Pesticide Poisoning at the Soonchunhyang University Chunan Hospital. The authors assessed paraquat exposure by quantifying the amount of ingested paraquat and by semiquantitative assay of paraquat in urine. Outcomes of paraquat intoxication were categorized as recovery or death. Among all the patients, 139 (90.3%) were transferred from other medical facilities to the Institute of Pesticide Poisoning following a mean exposure time of 20.1 hr (standard deviation = 2.6 hr). Intentional ingestion of paraquat accounted for 73.4% (113/154 patients) of all paraquat poisonings, and it represented a significantly higher fatality rate (53.2%) than did accidental ingestion (19.1 % [p < .001]). The overall paraquat fatality was 43.8%. Multiple logistic-regression analysis revealed that the risk of fatality increased significantly with (1) the quantity of paraquat ingested and (2) a positive urinary paraquat test. The results indicated that paraquat is potentially lethal in humans, and the risk of fatality is directly related to the amount ingested and absorbed.     

Anticancer effect of genistein on BG-1 ovarian cancer growth induced by 17 β-estradiol or bisphenol A via the suppression of the crosstalk between estrogen receptor alpha and insulin-like growth factor-1 receptor signaling pathways

The interaction between estrogen receptor (ER) and insulin-like growth factor-1 receptor (IGF-1R) signaling pathway plays an important role in proliferation of and resistance to endocrine therapy to estrogen dependent cancers. Estrogen (E2) upregulates the expression of components of IGF-1 system and induces the downstream of mitogenic signaling cascades via phosphorylation of insulin receptor substrate-1 (IRS-1). In the present study, we evaluated the xenoestrogenic effect of bisphenol A (BPA) and antiproliferative activity of genistein (GEN) in accordance with the influence on this crosstalk. BPA was determined to affect this crosstalk by upregulating mRNA expressions of ERα and IGF-1R and inducing phosphorylation of IRS-1 and Akt in protein level in BG-1 ovarian cancer cells as E2 did. In the mouse model xenografted with BG-1 cells, BPA significantly increased a tumor burden of mice and expressions of ERα, pIRS-1, and cyclin D1 in tumor mass compared to vehicle, indicating that BPA induces ovarian cancer growth by promoting the crosstalk between ER and IGF-1R signals. On the other hand, GEN effectively reversed estrogenicity of BPA by reversing mRNA and protein expressions of ERα, IGF-1R, pIRS-1, and pAkt induced by BPA in cellular model and also significantly decreased tumor growth and in vivo expressions of ERα, pIRS-1, and pAkt in xenografted mouse model. Also, GEN was confirmed to have an antiproliferative effect by inducing apoptotic signaling cascades. Taken together, these results suggest that GEN effectively reversed the increased proliferation of BG-1 ovarian cancer by suppressing the crosstalk between ERα and IGF-1R signaling pathways upregulated by BPA or E2.