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81.
Elaine A Merrill Rebecca A Clewell Peter J Robinson Annie M Jarabek Jeffery M Gearhart Teresa R Sterner Jeffrey W Fisher 《Toxicological sciences》2005,83(1):25-43
Detection of perchlorate (ClO4-) in several drinking water sources across the U.S. has lead to public concern over health effects from chronic low-level exposures. Perchlorate inhibits thyroid iodide (I-) uptake at the sodium (Na+)-iodide (I-) symporter (NIS), thereby disrupting the initial stage of thyroid hormone synthesis. A physiologically based pharmacokinetic (PBPK) model was developed to describe the kinetics and distribution of both radioactive I- and cold ClO4- in healthy adult humans and simulates the subsequent inhibition of thyroid uptake of radioactive I- by ClO4-. The model successfully predicts the measured levels of serum and urinary ClO4- from drinking water exposures, ranging from 0.007 to 12 mg ClO4-/kg/day, as well as the subsequent inhibition of thyroid 131I- uptake. Thyroid iodine, as well as total, free, and protein-bound radioactive I- in serum from various tracer studies, are also successfully simulated. This model's parameters, in conjunction with corresponding model parameters established for the male, gestational, and lactating rat, can be used to estimate parameters in a pregnant or lactating human, that have not been or cannot be easily measured to extrapolate dose metrics and correlate observed effects in perchlorate toxicity studies to other human life stages. For example, by applying the adult male rat:adult human ratios of model parameters to those parameters established for the gestational and lactating rat, we can derive a reasonable estimate of corresponding parameters for a gestating or lactating human female. Although thyroid hormones and their regulatory feedback are not incorporated in the model structure, the model's successful prediction of free and bound radioactive I- and perchlorate's interaction with free radioactive I- provide a basis for extending the structure to address the complex hypothalamic-pituitary-thyroid feedback system. In this paper, bound radioactive I- refers to I- incorporated into thyroid hormones or iodinated proteins, which may or may not be bound to plasma proteins. 相似文献
82.
Donghong Wang Justine M Ritchie Elaine M Smith Zugui Zhang Lubomir P Turek Thomas H Haugen 《Cancer epidemiology, biomarkers & prevention》2005,14(3):626-632
In order to examine the association between alcohol dehydrogenase 3 (ADH3) genotypes and risk of head and neck squamous cell carcinomas (HNSCC), we conducted a hospital based case-control study including 348 cases and 330 controls. DNA isolated from exfoliated cells from the oral cavity were genotyped for ADH3 polymorphisms using PCR followed by SspI digestion. Odds ratios (OR) and hazards ratios (HR) were done by unconditional logistic regression and Cox regression. Relative to ADH3(2-2) carriers, ADH3(1-1) [OR, 0.7; 95% confidence interval (CI), 0.4-1.1] and ADH3(1-2) (OR, 0.8; 95% CI, 0.5-1.2) had a nonsignificant reduced risk of HNSCC. ADH(1-2) smokers of >30 pack-years were at decreased risk of oral cavity squamous cell carcinomas compared with ADH3(2-2) (OR, 0.3, 0.1-0.9), whereas ADH3(1-1) smokers were not. After adjustment, those with ADH3(1-2) had significantly worse overall survival compared with ADH3(1-1) (HR, 0.3, 0.2-0.6) or ADH3(2-2) (HR, 0.4, 0.2-0.9) and increased recurrence (ADH3(1-1), 0.2, 0.1-0.6; ADH3(2-2), 0.6, 0.2-1.3). Our data did not show that ADH3 genotypes had a significantly independent effect on the risk of HNSCC, nor did they modify the risks increased by alcohol or tobacco consumption and high-risk human papillomavirus infection. However, participants with ADH3(1-2) genotype were associated with poorer survival compared with those who had the other two ADH3 genotypes and a higher rate of recurrence than participants with ADH3(1-1) genotype. 相似文献
83.
Terryl J Hartman Binbing Yu Paul S Albert Martha L Slattery Electra Paskett James Walter Kikendall Frank Iber Brenda K Brewer Arthur Schatzkin Elaine Lanza 《Cancer epidemiology, biomarkers & prevention》2005,14(10):2359-2365
The Polyp Prevention Trial was designed to evaluate the effects of a high-fiber (18 g/1,000 kcal), high-fruit and -vegetable (3.5 servings/1,000 kcal), low-fat (20% energy) diet on recurrence of adenomatous polyps. Participants > or =35 years of age, with histologically confirmed colorectal adenoma(s) removed in the prior 6 months, were randomized to the intervention or control group. Demographic, dietary, and clinical information, including use of nonsteroidal anti-inflammatory drugs (NSAID), was collected at baseline and four annual visits. Adenoma recurrence was found in 754 of 1,905 participants and was not significantly different between groups. NSAID use was associated with a significant reduction in recurrence [odds ratio (OR), 0.77; 95% confidence interval (95% CI), 0.63-0.95]. In this analysis, NSAIDs modified the association between the intervention and recurrence at baseline (P = 0.02) and throughout the trial (P = 0.008). Among participants who did not use NSAIDs, the intervention was in the protective direction but did not achieve statistical significance (OR, 0.87; 95% CI, 0.69-1.09). The intervention was protective among males who did not use NSAIDs at baseline (OR, 0.71; 95% CI, 0.54-0.94), but not among NSAIDs users (OR, 1.09; 95% CI, 0.74-1.62). For females, corresponding OR estimates were 1.28 (95% CI, 0.86-1.90) and 2.30 (95% CI, 1.24-4.27), respectively. The protective association observed for NSAID use was stronger among control (OR, 0.63; 95% CI, 0.47-0.84) than for intervention group participants (OR, 0.97; 95% CI, 0.74-1.28). These results should be interpreted cautiously given that they may have arisen by chance in the course of examining multiple associations and Polyp Prevention Trial study participants were not randomly assigned to both dietary intervention and NSAID use. Nevertheless, our results suggest that adopting a low-fat, high-fiber diet rich in fruits and vegetables may lower the risk of colorectal adenoma recurrence among individuals who do not regularly use NSAIDs. 相似文献
84.
Rosalie M Luiten Esther W M Kueter Wolter Mooi Maarten P W Gallee Elaine M Rankin Winald R Gerritsen Shirley M Clift Willem J Nooijen Pauline Weder Willeke F van de Kasteele Johan Sein Paul C M van den Berk Omgo E Nieweg Anton M Berns Hergen Spits Gijsbert C de Gast 《Journal of clinical oncology》2005,23(35):8978-8991
PURPOSE: To determine the feasibility, toxicity, and immunologic effects of vaccination with autologous tumor cells retrovirally transduced with the GM-CSF gene, we performed a phase I/II vaccination study in stage IV metastatic melanoma patients. PATIENTS AND METHODS: Sixty-four patients were randomly assigned to receive three vaccinations of high-dose or low-dose tumor cells at 3-week intervals. Tumor cell vaccine preparation succeeded for 56 patients (88%), but because of progressive disease, the well-tolerated vaccination was completed in only 28 patients. We analyzed the priming of T cells against melanoma antigens, MART-1, tyrosinase, gp100, MAGE-A1, and MAGE-A3 using human leukocyte antigen/peptide tetramers and functional assays. RESULTS: The high-dose vaccination induced the infiltration of T cells into the tumor tissue. Three of 14 patients receiving the high-dose vaccine showed an increase in MART-1- or gp100-specific T cells in the peripheral blood during vaccination. Six patients experienced disease-free survival for more than 5 years, and two of these patients developed vitiligo at multiple sites after vaccination. MART-1- and gp100-specific T cells were found infiltrating in vitiligo skin. Upon vaccination, the T cells acquired an effector phenotype and produced interferon-gamma on specific antigenic stimulation. CONCLUSION: We conclude that vaccination with GM-CSF-transduced autologous tumor cells has limited toxicity and can enhance T-cell activation against melanocyte differentiation antigens, which can lead to vitiligo. Whether the induction of autoimmune vitiligo may prolong disease-free survival of metastatic melanoma patients who are surgically rendered as having no evidence of disease before vaccination is worthy of further investigation. 相似文献
85.
Karen D. Wright MD MS Mihaela M. Onciu MD Elaine Coustan‐Smith MS Dario Campana MD PhD Susana C. Raimondi PhD Hiroto Inaba MD PhD Raul Ribeiro MD Ching‐Hon Pui MD John T. Sandlund MD 《Pediatric blood & cancer》2013,60(7):E38-E41
Dendritic cell leukemia (DCL) or hematodermic tumor is an uncommon subtype of acute leukemia. In contrast to adult cases, children tend to have a less aggressive course. The diagnosis of DCL should be considered when its characteristic morphologic features are present and leukemic cells co‐express CD4 and CD56. Cases of DCL among pediatric patients have been reported to respond to therapeutic regimens for acute lymphoblastic leukemia, but details regarding the specifics of therapy are lacking. Pediatr Blood Cancer 2013; 60: E38–E41. © 2013 Wiley Periodicals, Inc. 相似文献
86.
Chi-Man Koon Subiyanto Fong Elaine Wat Yan-Ping Wang David Wing-Shing Cheung Clara Bik-San Lau Ping-Chung Leung Han-Dong Sun Qin-Shi Zhao Kwok-Pui Fung 《Journal of ethnopharmacology》2014
Ethnopharmacological relevance
Erigerontis Herba is widely used as a traditional Chinese medicine and is commonly used for neuroprotection and vascular protection.Aim of study
In this study, the vasodilator effects of Erigerontis Herba (DZXX) were investigated using rat isolated aorta rings.Material and method
The involvement of endothelium in the vasorelaxation was studied by comparing response of endothelium-intact and endothelium-denuded aorta rings which precontracted with U46619. The involvement of K+ channels was studied by pretreatment of the aorta rings with various K+ channel inhibitors. The involvement of Ca2+ channel was studied by incubating aorta rings with Ca2+-free solution, primed with U46619 prior to elicit contraction by addition of Ca2+ solution.Results
DZXX (0.2–2 mg/ml) induced a concentration-dependent relaxation on U44619-precontracted aorta rings with EC50 of 0.354±0.036 mg/ml. Removal of endothelium or pretreatment with a BKCa inhibitor iberiotoxin, KIR inhibitor barium chloride or Kv inhibitor 4-aminopyridine produced no effect on the DZXX-induced vasorelaxation. However, pretreatment with a KATP inhibitor glibenclamide or a non-selective K+ channel inhibitor tetraethylammonium produced significant inhibition on the DZXX-induced vasorelaxation by 29.9% and 21.3%, respectively. Pretreatment with DZXX (0.4, 1.2 and 2 mg/ml) produced a concentration-dependent inhibition on Ca2+-induced vasoconstriction.Conclusions
These results suggest that the vasodilator effect of DZXX was endothelium-independent, mediated by decreasing the influx of Ca2+ by calcium channel inhibition and increasing the influx of K+ by opening of a KATP channel. 相似文献87.
88.
André São Pedro Renan Fernandes Cristiane Flora Villarreal Rosana Fialho Elaine Cabral Albuquerque 《Journal of microencapsulation》2016,33(1):18-29
Context Opioids have been used as the reference treatment on chronic pain. However, they are related to serious adverse effects which affect the patient compliance to treatment, as well as, his quality of life. Particulate formulations have been investigated as an alternative to improve opioid efficacy and safety. Objective Summarise the available studies concerning micro and nanoencapsulated opioid formulations discussing their biopharmaceutical characteristics, such as composition, size, in vitro release, pharmacokinetic and antinociceptive profile. Methods Papers available in 1995–2015 at Medline, Science Direct and Web of Science databases were collected and assessed. Searches were performed using varied combinations of the keywords of this work. Results Opioid-loaded particles showed prolonged drug release with maintenance of serum therapeutic concentrations and extended analgesia when compared with the free drugs. The side effects incidences were reduced or maintained the same. Conclusion Particulate formulations can significantly increase both potency and safety profiles of opioids. 相似文献
89.
Confirmation of genetic variants associated with lethal prostate cancer in a cohort of men from hereditary prostate cancer families 下载免费PDF全文
Qianchuan He Laura McIntosh Jonathan L. Wright Elaine A. Ostrander Ziding Feng Janet L. Stanford 《International journal of cancer. Journal international du cancer》2015,136(9):2166-2171
Germline genetic variants have been suggested as prognostic biomarkers for identifying patients at high risk for lethal prostate cancer (PCa). Validation studies have confirmed the association of several single nucleotide polymorphisms (SNPs) with fatal PCa, but whether these variants affect PCa‐specific mortality (PCSM) in patients with an inherited predisposition to PCa, based on familial history, is unknown. For this study, a cohort of 957 PCa patients from 270 hereditary prostate cancer families of European ancestry was genotyped for a panel of 22 PCSM‐associated SNPs. Death certificates were reviewed to confirm cause of death. Mixed‐effect Cox proportional hazards models were used to assess survival according to genotypes, accounting for relatedness and clinicopathological factors. Within this cohort, 98 PCa deaths were confirmed over an average follow‐up period of 12.7 years after diagnosis. Variant allele carriers for three SNPs had significantly altered risk for PCSM [rs635261 at RNASEL, hazard ratio (HR), 0.35, 95% CI, 0.18–0.66; p = 0.002; rs915927 in XRCC1, HR, 1.91, 95% CI, 1.21–3.02; p = 0.009; and rs2494750 at AKT1, HR, 0.45, 95% CI, 0.23–0.90; p = 0.016). These results confirm the association of genetic variation in three genes with PCa lethality in a cohort of men with an inherited susceptibility to the disease and provide validation evidence that germline SNPs provide prognostic information for PCa patients. Development of a panel of germline biomarkers with clinical utility for distinguishing patients at detection who have an increased risk for fatal PCa is warranted. 相似文献
90.
OBJECTIVE: To assess the utilization rates of and complications associated with inpatient hysterectomy in California between 1991 and 2004. METHODS: We used the California Patient Discharge Database to analyze International Classification of Diseases, 9th Revision, Clinical Modification diagnostic and procedure codes for 649,758 women undergoing inpatient hysterectomy in California between 1991 and 2004 using multiple logistic regression models. RESULTS: Between 1991 and 2004, the incidence of any type of inpatient hysterectomy for benign gynecologic conditions declined 17.6%. The rates of laparoscopically assisted vaginal hysterectomy and subtotal hysterectomy increased substantially. The year of hysterectomy was a factor associated with both medical and surgical complications; the odds of inpatient complications between 1991 and 2004 steadily declined. CONCLUSION: In California between 1991 and 2004, the incidence of inpatient hysterectomy for benign gynecological conditions and the adjusted odds of complications declined substantially. Changes in practice and shorter hospital stays may have affected the changes in inpatient hysterectomy rates and associated inpatient complications. 相似文献