tbuckley/cabot-search huggingface dataset:
Silibinin Protects against Photocarcinogenesis via Modulation of Cell Cycle Regulators, Mitogen-Activated Protein Kinases, and Akt Signaling
Authors: Gu Mallikarjuna, Sivanandhan Dhanalakshmi, Rana P. Singh, Chapla Agarwal, Rajesh Agarwal
Journal: Cancer Research (2004)

Abstract Here, we assessed the protective effect of silibinin on UVB-induced skin carcinogenesis in SKH-1 hairless mice. Topical application of silibinin before or immediately after UVB exposure or its dietary feeding resulted in a strong protection against photocarcinogenesis, in terms of tumor multiplicity (60–66%; P &amp;lt; 0.001), tumor volume per mouse (93–97%; P &amp;lt; 0.001) and tumor volume per tumor (80–91%; P &amp;lt; 0.001). Silibinin also moderately inhibited tumor incidence (5–15%; P &amp;lt; 0.01) and delayed tumor latency period (up to 4 weeks; P &amp;lt; 0.01–0.001). To investigate in vivo molecular mechanisms of silibinin efficacy, tumors and uninvolved skin from tumor-bearing mice were examined immunohistochemically for proliferation, p53, apoptosis, and activated caspase-3. Silibinin treatment showed a strong decrease (P &amp;lt; 0.001) in proliferating cell nuclear antigen-positive cells and an increase in p53-positive (P &amp;lt; 0.005–0.001), terminal deoxynucleotidyltransferase-mediated nick end labeling-positive (P &amp;lt; 0.005–0.001), and cleaved caspase-3–positive cells (P &amp;lt; 0.001). Western blot analysis of normal skin and tumor lysates showed that silibinin decreases the levels of cyclin-dependent kinase 2 and cyclin-dependent kinase 4 and associated cyclins A, E, and D1, together with an up-regulation of Cip1/p21, Kip1/p27, and p53. Silibinin also showed a strong phosphorylation of extracellular signal-regulated protein kinase 1/2, stress-activated protein kinase/c-JUN NH2-terminal kinase 1/2, and p38 mitogen-activated protein kinases but inhibited Akt phosphorylation and decreased survivin levels with an increase in cleaved caspase-3. Together, these results show a strong preventive efficacy of silibinin against photocarcinogenesis, which involves the inhibition of DNA synthesis, cell proliferation, and cell cycle progression and an induction of apoptosis. Furthermore, these results also identify in vivo molecular mechanisms of silibinin efficacy against photocarcinogenesis.
Effect of Human OGG1 1245C→G Gene Polymorphism on 8-Hydroxy-2′-Deoxyguanosine Levels of Leukocyte DNA among Patients Undergoing Chronic Hemodialysis
Authors: DER-CHERNG TARNG, TZUNG-JIUN TSAI, WEI-TING CHEN, TSUNG-YUN LIU, YAU-HUEI WEI
Journal: Journal of the American Society of Nephrology (2001)

The effects of the human OGG1 gene (hOGG1) 1245C→G polymorphism on the 8-hydroxy-2′-deoxyguanosine (8-OHdG) contents of peripheral leukocyte DNA were investigated among chronic hemodialysis patients. First, the hOGG1 1245C→G transversion was assessed, by using a PCR-restriction fragment length polymorphism method, among 210 hemodialysis patients and 156 healthy individuals. Second, the 8-OHdG contents in leukocyte DNA were measured, by using an HPLC-electrochemical detection method, for 112 hemodialysis patients and 112 age-, gender-, and genotype-matched healthy control subjects. The three genotypes (as dummy variables) and age, gender, dialysis duration, dialyzer membrane type, blood antioxidant levels, and iron parameters were used as independent variables and the natural logarithm of the leukocyte 8-OHdG concentration was used as a dependent variable in a forward, stepwise, multiple-regression model. The results demonstrated that the allelic frequency of hOGG1 1245G was 64.1% among 210 hemodialysis patients and 62.2% in the whole control population. The genotypic frequencies (CC/CG/GG ratio, 10%/51.9%/38.1%) for the hemodialysis patients did not differ significantly from those (16.7%/42.3%/41.0%) for the control subjects (P > 0.05, χ2 test). The mean leukocyte 8-OHdG levels for the patients were significantly higher than those for the healthy control subjects (P < 0.001). Leukocyte 8-OHdG levels were further increased among patients with the 1245GG genotype, compared with patients with the 1245CG or CC genotype (P < 0.001, ANOVA), but levels were similar among healthy control subjects irrespective of the hOGG1 gene polymorphism. It was also observed that patients who underwent dialysis with cellulose membranes exhibited significantly higher leukocyte 8-OHdG levels than did patients who underwent dialysis with polymethylmethacrylate, polysulfone, or vitamin E-bonded membranes (P < 0.001, ANOVA). The multivariate regression analysis revealed that hOGG1 1245C→G polymorphism and dialysis membrane type were the two independent predictors of 8-OHdG contents in leukocyte DNA from hemodialysis patients. This study demonstrated that the extent of oxidative DNA damage among chronic hemodialysis patients not only is influenced by overproduction of reactive oxygen species resulting from leukocyte contacts with complement-activating membranes and by impaired antioxidant defense mechanisms but also is genetically determined.
Cellular hypersensitivity to components of intestinal mucosa in ulcerative colitis and Crohn's disease
Authors: G. Bendixen
Journal: Gut (1969)

The migration of peripheral leucocytes in vitro is examined in 36 patients with ulcerative colitis, in 34 patients with Crohn's disease, in 12 patients with ulcerative colitis or Crohn's disease, and in 31 patients with other gastrointestinal disorders.In a majority of the patients with ulcerative colitis extracts of foetal, colonic, and jejunoileal mucosa inhibit migration of leucocytes.A similar reactivity is seldom seen in Crohn's disease.Extracts of liver, kidney, and adrenal gland do not in- hibit the migration.The reactivity of the ulcerative colitis group was found to be significantly different from that in controls and in the Crohn group, whereas the Crohn group did not differ significantly from the controls.The examination thus reveals a biological difference between ulcerative colitis and Crohn's disease, which are otherwise separable mainly on nosological criteria.The finding of a similar inhibition of leucocyte migration in five out of 31 patients with mis- cellaneous gastrointestinal disorders unrelated to ulcerative colitis and Crohn's disease was inconclusive.An antigen-induced inhibition of leucocyte migration has been shown in vitro to be a correlate of cellular hypersensitivity.The immunological mechanisms behind the present system are discussed, and it is concluded that the reactivity observed probably indicates the existence in ulcerative colitis of a state of cellular hypersensitivity to components of normal foetal, colonic, and jejunoileal mucosa.
Effect of the interplay between protein and surface on the properties of adsorbed protein layers
Authors: Myriam M. Ouberai, Kairuo Xu, Mark E. Welland
Journal: Biomaterials (2014)

Although protein adsorption to surface is a common phenomenon, investigation of the process is challenging due to the complexity of the interplay between external factors, protein and surface properties. Therefore experimental approaches have to measure the properties of adsorbed protein layers with high accuracy in order to achieve a comprehensive description of the process. To this end, we used a combination of two biosensing techniques, dual polarization interferometry and quartz crystal microbalance with dissipation. From this, we are able to extract surface coverage values, layer structural parameters, water content and viscoelastic properties to examine the properties of protein layers formed at the liquid/solid interface. Layer parameters were examined upon adsorption of proteins of varying size and structural properties, on surfaces with opposite polarity. We show that "soft" proteins such as unfolded α-synuclein and high molecular weight albumin are highly influenced by the surface polarity, as they form a highly diffuse and hydrated layer on the hydrophilic silica surface as opposed to the denser, less hydrated layer formed on a hydrophobic methylated surface. These layer properties are a result of different orientations and packing of the proteins. By contrast, lysozyme is barely influenced by the surface polarity due to its intrinsic structural stability. Interestingly, we show that for a similar molecular weight, the unfolded α-synuclein forms a layer with the highest percentage of solvation not related to surface coverage but resulting from the highest water content trapped within the protein. Together, these data reveal a trend in layer properties highlighting the importance of the interplay between protein and surface for the design of biomaterials.
Ferric Citrate Controls Phosphorus and Delivers Iron in Patients on Dialysis
Authors: Julia B. Lewis, Mohammed Sika, Mark J. Koury, Peale Chuang, Gerald Schulman, Mark T. Smith, Frederick C. Whittier, Douglas R. Linfert, Claude M. Galphin, Balaji P. Athreya, A. Kaldun Kaldun Nossuli, Ingrid J. Chang, Samuel S. Blumenthal, John Manley, Steven Zeig, Kotagal S. Kant, Juan Jose Olivero, Tom Greene, Jamie P. Dwyer
Journal: Journal of the American Society of Nephrology (2014)

Patients on dialysis require phosphorus binders to prevent hyperphosphatemia and are iron deficient. We studied ferric citrate as a phosphorus binder and iron source. In this sequential, randomized trial, 441 subjects on dialysis were randomized to ferric citrate or active control in a 52-week active control period followed by a 4-week placebo control period, in which subjects on ferric citrate who completed the active control period were rerandomized to ferric citrate or placebo. The primary analysis compared the mean change in phosphorus between ferric citrate and placebo during the placebo control period. A sequential gatekeeping strategy controlled study-wise type 1 error for serum ferritin, transferrin saturation, and intravenous iron and erythropoietin-stimulating agent usage as prespecified secondary outcomes in the active control period. Ferric citrate controlled phosphorus compared with placebo, with a mean treatment difference of -2.2±0.2 mg/dl (mean±SEM) (P<0.001). Active control period phosphorus was similar between ferric citrate and active control, with comparable safety profiles. Subjects on ferric citrate achieved higher mean iron parameters (ferritin=899±488 ng/ml [mean±SD]; transferrin saturation=39%±17%) versus subjects on active control (ferritin=628±367 ng/ml [mean±SD]; transferrin saturation=30%±12%; P<0.001 for both). Subjects on ferric citrate received less intravenous elemental iron (median=12.95 mg/wk ferric citrate; 26.88 mg/wk active control; P<0.001) and less erythropoietin-stimulating agent (median epoetin-equivalent units per week: 5306 units/wk ferric citrate; 6951 units/wk active control; P=0.04). Hemoglobin levels were statistically higher on ferric citrate. Thus, ferric citrate is an efficacious and safe phosphate binder that increases iron stores and reduces intravenous iron and erythropoietin-stimulating agent use while maintaining hemoglobin.
The Origin and Evolution of Mosquito APE Retroposons
Authors: James L. Crainey, Clare F. Garvey, Colin A. Malcolm
Journal: Molecular Biology and Evolution (2005)

The detection of horizontal transfer is important to understanding the origin and spread of transposable elements and in assessing their impact on genetic diversity. The occurrence of the phenomenon is not in doubt for two of the three major groups of elements, but is disputed for retroposons, largely on the grounds of data paucity and overreliance on divergence estimates between host species. We present here the most wide-ranging retroposon data set assembled to date for a species group, the mosquitoes. The results provide no evidence for horizontal transfer events and show conclusively that four previously reported events, involving Juan-A, Juan-C, T1, and Q, did not occur. We propose that the origin of all known mosquito retroposons can be attributed to vertical inheritance and that retroposons have therefore been a persistent source of genetic diversity in mosquito genomes since the emergence of the taxon. Furthermore, the data confirm that the unprecedented levels of retroposon diversity previously reported in Anopheles gambiae extends to at least seven other species representing five genera and all three mosquito subfamilies. Most notably, this included the L1 elements, which are not known in other insects. A number of novel well-defined monophyletic groups were also identified, particularly, JM2 and JM3 within the Jockey clade, which included sequences from seven and five mosquito species, respectively. As JM3 does not contain an Anopheles element, this represents a good example of stochastic loss and the best out of at least four found in this study. This exceptionally diverse data set when compared with the wealth of data available for the many unrelated species with which mosquitoes have intimate contact through blood feeding ought to be fertile ground for the discovery of horizontal transfer events. The absence of positive results therefore supports the view that retroposon horizontal transfer does not occur or is far more exceptional than for other types of transposable elements.
Author's response: understanding the natural progression in %FEV<sub>1</sub>decline in patients with cystic fibrosis: a longitudinal study
Authors: David Taylor-Robinson, Margaret Whitehead, Finn Diderichsen, Hanne Vebert Olesen, Tania Pressler, Rosalind Smyth, Peter Diggle
Journal: Thorax (2012)

We thank Professor Miller for his comments1 regarding our paper,2 in which we outline a novel approach to modelling repeated lung function measures in people with cystic fibrosis (CF) over long follow-up periods. We agree that it would be interesting to apply our methodology using alternative methods of expressing lung function across the age range, and reiterate that our approach can be usefully applied to any clinical …
Endothelial progenitor cells in ischemic stroke: an exploration from hypothesis to therapy
Authors: Ya-Feng Li, Li-Na Ren, Geng Guo, Lee Anne Cannella, Valeria Chernaya, Sonia Samuel, Su-Xuan Liu, Hong Wang, Xiao-Feng Yang
Journal: Journal of Hematology & Oncology (2015)

As the population ages and lifestyles change in concordance, the number of patients suffering from ischemic stroke and its associated disabilities is increasing. Studies on determining the relationship between endothelial progenitor cells (EPCs) and ischemic stroke have become a new hot spot and have reported that EPCs may protect the brain against ischemic injury, promote neurovascular repair, and improve long-term neurobehavioral outcomes. More importantly, they introduce a new perspective for prognosis assessment and therapy of ischemic stroke. However, EPCs' origin, function, influence factors, injury repair mechanisms, and cell-based therapy strategies remain controversial. Particularly, research conducted to date has less clinical studies than pre-clinical experiments on animals. In this review, we summarized and analyzed the current understanding of basic characteristics, influence factors, functions, therapeutic strategies, and disadvantages of EPCs as well as the regulation of inflammatory factors involved in the function and survival of EPCs after ischemic stroke. Identifying potential therapeutic effects of EPCs in ischemic stroke will be a challenging but an incredibly important breakthrough in neurology, which may bring promise for patients with ischemic stroke.
New guidelines for prevention and management of implantable cardiac electronic device-related infection
Authors: Jonathan A T Sandoe, Gavin Barlow, John B Chambers, Michael Gammage, Achyut Guleri, Philip Howard, Ewan Olson, John D Perry, Bernard D Prendergast, Michael J Spry, Richard P Steeds, Muzahir H Tayebjee, Richard Watkin
Journal: The Lancet (2015)
Pharmacogenetic Angiogenesis Profiling for First-line Bevacizumab plus Oxaliplatin-Based Chemotherapy in Patients with Metastatic Colorectal Cancer
Authors: Armin Gerger, Anthony El-Khoueiry, Wu Zhang, Dongyun Yang, Harpreet Singh, Pierre Bohanes, Yan Ning, Thomas Winder, Melissa J. LaBonte, Peter M. Wilson, Leonor Benhaim, David Paez, Rita El-Khoueiry, Gudrun Absenger, Heinz-Josef Lenz
Journal: Clinical Cancer Research (2011)

There is substantial germline genetic variability within angiogenesis pathway genes, thereby causing interindividual differences in angiogenic capacity and resistance to antiangiogenesis therapy. We investigated germline polymorphisms in genes involved in VEGF-dependent and -independent angiogenesis pathways to predict clinical outcome and tumor response in metastatic colorectal cancer (mCRC) patients treated with bevacizumab and oxaliplatin-based chemotherapy.A total of 132 patients treated with first-line bevacizumab and FOLFOX or XELOX were included in this study. Genomic DNA was isolated from whole-blood samples by PCR-RFLP or direct DNA sequencing. The endpoints of the study were progression-free survival (PFS), overall survival (OS), and response rate (RR).The minor alleles of EGF rs444903 A>G and IGF-1 rs6220 A>G were associated with increased OS and remained significant in multivariate Cox regression analysis (HR: 0.52; 95% CI: 0.31-0.87; adjusted P = 0.012 and HR: 0.60; 95% CI: 0.36-0.99; adjusted P = 0.046, respectively). The minor allele of HIF1α rs11549465 C>T was significantly associated with increased PFS but lost its significance in multivariate analysis. CXCR1 rs2234671 G>C, CXCR2 rs2230054 T>C, EGFR rs2227983 G>A, and VEGFR-2 rs2305948 C>T predicted tumor response, with CXCR1 rs2234671 G>C remaining significant in multiple testing (P(act) = 0.003).In this study, we identified common germline variants in VEGF-dependent and -independent angiogenesis genes predicting clinical outcome and tumor response in patients with mCRC receiving first-line bevacizumab and oxaliplatin-based chemotherapy.
Prediction of Nocturia Severity in Men
Authors: Daniel Nassau, Svetlana Avulova, Fara M. Friedman, Jeffrey P. Weiss, Jerry G. Blaivas
Journal: JAMA Surgery (2014)

Nocturia is one of the most common and bothersome of lower urinary tract symptoms.To examine the effect of race and metabolic risk factors on nocturia severity in men as measured by the number of nightly voids.A retrospective review from 2011 to 2013 was performed at a Veterans Affairs-based urology clinic in Brooklyn, New York, among 104 adult men 18 years or older who completed a 24-hour frequency and volume chart. Metabolic risk factors included race and a history of diabetes mellitus, hypertension, and obstructive sleep apnea. The 24-hour frequency and volume chart data included the nocturia index (nocturnal urine volume divided by maximal voided volume), the nocturnal polyuria index (nocturnal urine volume divided by 24-hour volume), and nocturnal urine production (nocturnal urine volume per hours slept). A nocturia index of less than 2 vs 2 or higher, a nocturnal polyuria index of less than 33% vs 33% or higher, and nocturnal urine production of less than 90 vs 90 mL/h or higher were chosen as clinically relevant cutoff points for nocturia severity. Nocturia severity was compared by race, the aforementioned variables, and the presence or absence of diabetes mellitus, hypertension, and obstructive sleep apnea.The number of nightly voids.One hundred four adult men (mean age, 64 years; age range, 24-92 years) completed a 24-hour frequency and volume chart (mean number of nightly voids, 2.93; range, 0-15). The number of nightly voids was not statistically different for white vs black race (3.00 vs 2.93, P = .86) or for the presence vs the absence of diabetes mellitus (3.00 vs 2.88, P = .85), hypertension (2.94 vs 2.80, P = .75), and obstructive sleep apnea (3.29 vs 2.83, P = .50). However, nocturia severity was significantly different based on a nocturia index of less than 2 vs 2 or higher (1.39 vs 3.60), a nocturnal polyuria index of less than 33% vs 33% or higher (1.83 vs 3.65), and nocturnal urine production of less than 90 vs 90 mL/h or higher (2.27 vs 3.77) (P < .001 for all).Neither race nor metabolic risk factors affect nocturia severity. In contrast, variables that denote nocturnal urine overproduction sharply discriminate the risk of nocturia severity and suggest that variable data may provide useful clinical correlation.
FEV6 as an alternative for FVC in detecting airflow obstruction in COPD patients undergoing six minute Walk test
Authors: Li-Fei Chen, Shu-Chuan Ho, Wen-Cing Jao, Te-Feng Sheng, Han-Pin Kuo, Chun-Hua Wang
Journal: European Respiratory Journal (2013)

Forced expiratory volume in 6 seconds (FEV6) could complement forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) for detecting airflow obstruction in chronic obstructive pulmonary disease (COPD). Our aim is to evaluate the use of the FEV1/ FEV6 and FEV6 as an alternative for FEV1/FVC and FVC in the detection of dynamic hyperinflation during six minute walk test (6MWT).

Sixty-two ambulatory and clinically-stable COPD patients were randomized to this cross-over study. One group of 31 patients performed the spirometry by FVC first, then measuring FEV6, before and after 6MWT. The other 31 patients initiated the maneuver of FEV6 first, then followed by FVC, during the 6MWT. FVC, FEV1, inspiratory capacity (IC), FEV6 and FEV1/FEV6 were recorded.

FEV6 and FEV1/FEV6 were strongly correlated with FVC (r=0.907, n=62, p<0.0001) and FEV1/FVC (r=0.865, n=62, p<0.0001) before 6MWT. Values of FEV6 and FEV1/FEV6 were also strongly related to FVC (r=1.00, n=62, p<0.0001) and FEV1/FVC (r=0.809, n=62, p<0.0001) after 6MWT. We found that FVC showed good correlation to pre-exercise IC (r=0.697, n=62, p<0.0001) and post-exercise IC (r=0.642, n=62, p<0.0001). The value of FEV6 also have similar correlation with pre-exercise IC (r=0.593, n=62, p<0.0001) and post-exercise IC (r=0.584, n=62, p<0.0001). The delta IC was correlated with delta FEV6 (r=-0.357, n=62, p=0.004), however, was not related to delta FVC (r=-0.093,n=62, p=0.470).In conclusion, FEV6 and FEV1/FEV6 can be used as a valid alternative for FVC and FEV1/FVC to detect airway limitation or dynamic hyperinflation during 6MWT.
Treatment of hepatocellular carcinoma associated with advanced cirrhosis by transcatheter arterial chemoembolization using autologous blood clot: A preliminary report
Authors: Toshiaki Gunji, Nobuo Kawauchi, Shin Ohnishi, Takashi Ishikawa, Hitoshi Nakagama, Takashi Kaneko, Takashi Moriyama, Nobuyuki Matsuhashi, Yoshio Yazaki, Michio Imawari
Journal: Hepatology (1992)

Twenty-two patients with hepatocellular carcinoma were treated by a new method of transcatheter arterial chemoembolization using an autologous blood clot as an embolizing agent. All had underlying advanced cirrhosis (14 Child's class B and 8 Child's class C patients). The median follow-up interval was 11 mo (range = 2 to 30 mo). The results of the treatment were compared with those of conventional chemoembolization using gelatin sponge particles for 19 Child's class B patients as historical controls. The survival rate for Child's class B patients treated by the new procedure estimated by the Kaplan-Meier method was 100% at 2 yr, whereas the survival rate for Child's class B patients treated by conventional chemoembolization was 89% at 1 yr and 72% at 2 yr. The survival rate for Child's class C patients was 75% at 1 yr and 50% at 2 yr. Side effects such as pyrexia of more than 38 degrees C or an elevation of the serum bilirubin level of more than 1.5-fold were less common in patients treated by the new method than in those treated by conventional chemoembolization, and thus the new procedure could be performed even for Child's class C patients. The autologous blood clot did not collapse the hepatic arteries even when the embolization was performed repeatedly, and thus fine collateral vessels feeding recurrent hepatocellular carcinoma did not develop. The results suggest that the new chemoembolization using an autologous blood clot is a promising therapeutic procedure in the management of hepatocellular carcinoma associated with advanced cirrhosis.