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31.
Association of total tau and phosphorylated tau 181 protein levels in cerebrospinal fluid with cerebral atrophy in mild cognitive impairment and Alzheimer disease
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Philipp A. Thomann Elmar Kaiser Peter Schnknecht Johannes Pantel Marco Essig Johannes Schrder 《Journal of psychiatry & neuroscience : JPN》2009,34(2):136-142
Background
We sought to examine the association of levels of total tau (t-tau) and phosphorylated tau 181 (p-tau181) protein with brain morphology in mild cognitive impairment, as defined by the concept of aging-associated cognitive decline (AACD) and Alzheimer disease.Methods
Twenty-three participants with AACD, 16 with Alzheimer disease and 15 healthy controls underwent magnetic resonance imaging and lumbar puncture. We performed voxel-based morphometry to investigate the association between tau levels in cerebrospinal fluid (CSF) and cerebral grey matter density throughout the entire brain.Results
Voxel-based morphometry revealed that both elevated t-tau and p-tau181 concentrations were associated with reduced grey matter density in temporal, parietal and frontal regions. Among participants with AACD, elevated levels of p-tau181 (but not t-tau) in CSF were correlated with a pronounced atrophy in the right hippocampus.Limitations
Our study was limited by the small sample, especially with respect to the analysis comprising the AACD subgroups. Moreover, we did not correct our voxel-based morphometry analyses for multiple dependent comparisons, therefore they harbour a risk of false-positive results.Conclusion
Elevated levels of t-tau and p-tau181 in CSF reflect degenerative processes in the cortical regions typically affected in Alzheimer disease. Our findings in participants with AACD support the hypothesis that p-tau181 might be more specifically related to neurodegenerative changes in early Alzheimer disease. 相似文献32.
Cizao Ren Pantel S Vokonas Helen Suh Shona Fang David C Christiani Joel Schwartz 《Environmental health : a global access science source》2010,9(1):78
Background
Air pollution is associated with adverse human health, but mechanisms through which pollution exerts effects remain to be clarified. One suggested pathway is that pollution causes oxidative stress. If so, oxidative stress-related genotypes may modify the oxidative response defenses to pollution exposure. 相似文献33.
Hemoglobin Affinity for Oxygen in the Anginal Syndrome with Normal Coronary Arteriograms 总被引:1,自引:0,他引:1
Pantel S. Vokonas Peter F. Cohn Michael D. Klein Myron B. Laver Richard Gorlin 《The Journal of clinical investigation》1974,54(2):409-415
Oxyhemoglobin dissociation (OHD) curves were performed on whole blood (WB) from 20 patients with anginal pain, normal hemodynamics, and normal coronary arteries, as demonstrated by selective coronary cinearteriography. OHD curves in 19 of 20 patients, from zero to full saturation, were nearly identical to those in normal control subjects with values for P(50) (Po(2) at 50% saturation and pH 7.4) of 26.7+/-1.5 (mean+/-SD of the mean) torr (mm Hg) and red blood cell (RBC) levels of 2,3-diphosphoglyceric acid (2, 3-DPG) of 0.72+/-0.10 (mean+/-SD of the mean) M/M hemoglobin (Hb). Normal values for nonsmoking adults were: P(50), 26.6+/-1.4 (mean+/-SD of the mean) torr: and RBC 2,3-DPG, 0.81+/-0.09 (mean+/-SD of the mean) M/M Hb. Mean levels of carbon monoxide were normal at 0.14+/-0.01 (mean+/-SEM) ml/100 ml WB in 10 patients who were nonsmokers and 0.45+/-0.15 (mean+/-SEM) ml/100 ml WB in 10 smokers. In one patient, a heavy smoker with markedly elevated blood carbon monoxide levels, an abnormal leftward shift of the OHD curve was observed. This was corrected after discontinuation of smoking. In utilizing these methods, we could not detect consistent abnormalities of Hb affinity for oxygen at rest in the patients studied, which suggests that a defect in oxygen transport at rest is an unlikely explanation for the symptoms of chest pain in patients with the anginal syndrome and normal coronary arteriograms. 相似文献
34.
J. E. Gschwend P. Albers M. Bögemann P. Goebell A. Heidenreich J. Klier F. König S. Machtens K. Pantel C. Thomas 《Der Urologe. Ausg. A》2018,57(1):34-39
Background
At the 2016 ASCO annual meeting, new data from two randomized phase III studies concerning taxane-based chemotherapy as a treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC) were presented.Objectives
The focus is on the clinical impact of these data.Materials and methods
A group of German experts in the field of urogenital–oncologic expertise discussed the clinical impact with respect to the current data.Results
The study results support the current clinical data. They confirm the efficacy and safety of cabazitaxel beyond first-line therapy with docetaxel for patients with mCRPC.Conclusions
Cabazitaxel is an important treatment option after docetaxel progression. With respect to the performance status of a patient, it is adequate to reduce the dosage to 20?mg/m2 cabazitaxel.35.
Zhu ZZ Sparrow D Hou L Tarantini L Bollati V Litonjua AA Zanobetti A Vokonas P Wright RO Baccarelli A Schwartz J 《Cancer causes & control : CCC》2011,22(3):437-447
Background
Global genomic hypomethylation is a common epigenetic event in cancer that mostly results from hypomethylation of repetitive DNA elements. Case?Ccontrol studies have associated blood leukocyte DNA hypomethylation with several cancers. Because samples in case?Ccontrol studies are collected after disease development, whether DNA hypomethylation is causal or just associated with cancer development is still unclear.Methods
In 722 elderly subjects from the Normative Aging Study cohort, we examined whether DNA methylation in repetitive elements (Alu, LINE-1) was associated with cancer incidence (30 new cases, median follow-up: 89 months), prevalence (205 baseline cases), and mortality (28 deaths, median follow-up: 85 months). DNA methylation was measured by bisulfite pyrosequencing.Results
Individuals with low LINE-1 methylation (36.
Carina Roth Klaus Pantel Volkmar Müller Brigitte Rack Sabine Kasimir-Bauer Wolfgang Janni Heidi Schwarzenbach 《BMC cancer》2011,11(1):4
Background
As cell-free circulating DNA exists predominantly as mono- and oligonucleosomes, the focus of the current study was to examine the interplay of circulating nucleosomes, DNA, proteases and caspases in blood of patients with benign and malignant breast diseases. 相似文献37.
Sung Kyun Park Howard Hu Robert O. Wright Joel Schwartz Yawen Cheng David Sparrow Pantel S. Vokonas Marc G. Weisskopf 《Environmental health perspectives》2009,117(1):80-85
Background
Cumulative exposure to lead has been shown to be associated with depression of electrocardiographic conduction, such as QT interval (time from start of the Q wave to end of the T wave). Because iron can enhance the oxidative effects of lead, we examined whether polymorphisms in iron metabolism genes [hemochromatosis (HFE), transferrin (TF) C2, and heme oxygenase-1 (HMOX-1)] increase susceptibility to the effects of lead on QT interval in 613 community-dwelling older men.Methods
We used standard 12-lead electrocardiograms, K-shell X-ray fluorescence, and graphite furnace atomic absorption spectrometry to measure QT interval, bone lead, and blood lead levels, respectively.Results
A one-interquartile-range increase in tibia lead level (13 μg/g) was associated with a 11.35-msec [95% confidence interval (CI), 4.05–18.65 msec] and a 6.81-msec (95% CI, 1.67–11.95 msec) increase in the heart-rate–corrected QT interval among persons carrying long HMOX-1 alleles and at least one copy of an HFE variant, respectively, but had no effect in persons with short and middle HMOX-1 alleles and the wild-type HFE genotype. The lengthening of the heart-rate–corrected QT interval with higher tibia lead and blood lead became more pronounced as the total number (0 vs. 1 vs. ≥2) of gene variants increased (tibia, p-trend = 0.01; blood, p-trend = 0.04). This synergy seems to be driven by a joint effect between HFE variant and HMOX-1 L alleles.Conclusion
We found evidence that gene variants related to iron metabolism increase the impacts of low-level lead exposure on the prolonged QT interval. This is the first such report, so these results should be interpreted cautiously and need to be independently verified. 相似文献38.
39.
Schwarzenbach H Chun FK Lange I Carpenter S Gottberg M Erbersdobler A Friedrich MG Huland H Pantel K 《International journal of cancer. Journal international du cancer》2007,120(7):1465-1471
Tumor tissues, blood plasma and bone marrow (BM) aspirates of 57 prostate cancer patients (PCa) without clinical signs of overt metastases were assessed for LOH (loss of heterozygosity) by a PCR-based fluorescence microsatellite analysis, using a panel of 15 markers. Additionally, micrometastatic tumor cells in BM were monitored by an immunocytological cytokeratin assay. In total, 25 (44%), 32 (56%) and 41 (72%) of the patients had at least 1 LOH in their blood, BM and tumor samples, respectively. Among the informative cases, the frequency of LOH was highest in blood plasma for the markers D8S360 (18%) and D10S1765 (15%), and in BM plasma for THRB (24%) and D8S137 (22%). Comparison of blood plasma and BM with tumors showed discrepant results in 35% and 45% of patients, respectively. Whereas all LOHs at THRB in BM plasma were also detected in the autologous tumor tissues, LOHs at D6S474 and D11S898 in BM were not retrieved in the tumors. The comparison with established risk factors showed a correlation of borderline significance for LOH at D9S1748 in the BM aspirates (p=0.055) and a significant correlation in the tumor samples (p=0.004) with increasing pathologic Gleason scores. Interestingly, 22% of the PCa patients harbored tumor cells in their BM and tended (p=0.065) to have more frequent LOH (16%) in BM plasma compared to patients without tumor cells (9%). These data demonstrate, for the first time, the presence of free tumor-specific DNA in blood and BM of PCa patients and suggest a possible relationship to BM micrometastasis. 相似文献
40.
Park SK O'Neill MS Stunder BJ Vokonas PS Sparrow D Koutrakis P Schwartz J 《Journal of exposure science & environmental epidemiology》2007,17(5):488-497
Although many studies report that exposure to air pollution harms health, few have examined associations between pollution sources and health outcomes. We hypothesized that pollution originating in different locations has different associations with heart rate variability (HRV) among 497 men from the Normative Aging Study in Boston, Massachusetts. We identified the paths that air masses traveled ('back-trajectories') before arriving in Boston on the days the men were examined. Next, we classified these trajectories into six clusters. We examined whether the association of measured air pollutants with HRV (standard deviation of normal-to-normal intervals, high-frequency power (HF) and low-frequency power (LF), and LF/HF ratio) differed by cluster. We also examined whether the clusters alone (not considering air pollution measurements) showed different associations with HRV. The effects of black carbon (BC) on all HRV measures were strongest on days with southwest trajectories. Subjects who were examined on days where air parcels came from west had the strongest associations with ozone. All particle pollutants (particulate matter <2.5 microm in aerodynamic diameter (PM2.5), BC, and sulfates) were associated with increased LF/HF ratio on days with relatively short trajectories, which are related to local, slow-moving air masses. We also observed significant increases in LF/HF in days where air came from the northwest and west, compared to north trajectory days. Health effects associated with exposure to air pollution can be evaluated using pollutant concentrations as well as aspects of the pollution mixture captured by identifying locations where air masses originate. Independent effects of both these indicators of pollution exposure were seen on cardiac autonomic function. 相似文献