tbuckley/cabot-search huggingface dataset:
Ferric Citrate Reduces Intravenous Iron and Erythropoiesis-Stimulating Agent Use in ESRD
Authors: Kausik Umanath, Diana I. Jalal, Barbara A. Greco, Ebele M. Umeukeje, Efrain Reisin, John Manley, Steven Zeig, Dana G. Negoi, Anand N. Hiremath, Samuel S. Blumenthal, Mohammed Sika, Robert Niecestro, Mark J. Koury, Khe-Ni Ma, Tom Greene, Julia B. Lewis, Jamie P. Dwyer
Journal: Journal of the American Society of Nephrology (2015)

Ferric citrate (FC) is a phosphate binder with shown efficacy and additional effects on iron stores and use of intravenous (iv) iron and erythropoiesis-stimulating agents (ESAs). We provide detailed analyses of changes in iron/hematologic parameters and iv iron/ESA use at time points throughout the active control period of a phase 3 international randomized clinical trial. In all, 441 subjects were randomized (292 to FC and 149 to sevelamer carbonate and/or calcium acetate [active control (AC)]) and followed for 52 weeks. Subjects on FC had increased ferritin and transferrin saturation (TSAT) levels compared with subjects on AC by week 12 (change in ferritin, 114.1±29.35 ng/ml; P<0.001; change in TSAT, 8.62%±1.57%; P<0.001). Change in TSAT plateaued at this point, whereas change in ferritin increased through week 24, remaining relatively stable thereafter. Subjects on FC needed less iv iron compared with subjects on AC over 52 weeks (median [interquartile range] dose=12.9 [1.0–28.9] versus 26.8 [13.4–47.6] mg/wk; P<0.001), and the percentage of subjects not requiring iv iron was higher with FC (P<0.001). Cumulative ESA over 52 weeks was lower with FC than AC (median [interquartile range] dose=5303 [2023–9695] versus 6954 [2664–12,375] units/wk; P=0.04). Overall, 90.3% of subjects on FC and 89.3% of subjects on AC experienced adverse events. In conclusion, treatment with FC as a phosphate binder results in increased iron parameters apparent after 12 weeks and reduces iv iron and ESA use while maintaining hemoglobin over 52 weeks, with a safety profile similar to that of available binders.
Abstract 2612: Tumor associated microvesicles confer neoplastic transformation of patient derived adipose stem cells .
Authors: Zakaria Y. Abd Elmageed, Yijun Yang, Raju Thomas, Krishnarao Moparty, Manish Ranjan, Debasis Mondal, Krzysztof Moroz, Oliver Sartor, Asim B. Abdel-Mageed
Journal: Cancer Research (2013)

Abstract Background: Unraveling the underlying mechanisms of prostate tumor growth and metastasis is critical to developing curative therapies currently unavailable for castration-resistant prostate cancer (CRPC). Obesity has been linked to increased risks of PC progression. Emerging evidence suggests that adipose-derived stem cells (ASCs) are often recruited to and promote tumor growth via unknown mechanisms. Methods: Patient derived ASCs (pASCs) with tumor homing potential were enriched and treated with condition media (CM) or microvesicles (MVs) of PC (C4-2B, PC-3) or normal prostate epithelial (RWPE1) cells. CM or MV-primed pASCs were examined for their ability to form prostate tumors in vivo. Tumor formation was validated by histopathologic analysis, expression of neoplastic and vasculogenic markers, karyotyping and PC specific markers. LC/MS-MS, miRNA array, miRNA mimics and qRT-PCR analyses were employed to decipher the underling mechanistic roles of oncogenic RNAs and proteins of PC cell associated MVs in pASC tumor formation. Results: Herein, we report that PC cell microenvironment induces genotypic and phenotypic changes in pASCs and subverts them to undergo neoplastic transformation. Unlike normal counterparts, the pASCs primed with PC cell CM form neoplastic lesions in vivo and reproduce aggressive tumors in secondary recipients. The pASC tumors acquire cytogenetic aberrations and express epithelial, neoplastic and vasculogenic markers reminiscent of molecular features of PC tumor xenografts and mesenchymal-to-epithelial transition (MET). MVs derived from PC cell CM recapitulated prostate tumorigenic mimicry by pASCs in vivo. The oncogenic ‘reprogramming’ of pASCs is associated with PC cell-derived MVs transfer of oncomiRNAs (miR-125b, miR-130b, miR-155), H-Ras and K-Ras transcripts and Ras-related oncoproteins (RAB1A, RAB2A, RAB1B, RAB11A) and down-regulation of tumor suppressors Lats2 and PDCD4. Conclusion: Our findings establish previously uncharacterized mechanisms for tumor-derived MV-pASC axis in tumor formation, phenotypic variations in mesenchymal and epithelial states in tumor microenvironment, and in promoting tumor burden and metastasis in cancer patients. Citation Format: Zakaria Y. Abd Elmageed, Yijun Yang, Raju Thomas, Krishnarao Moparty, Manish Ranjan, Debasis Mondal, Krzysztof Moroz, Oliver Sartor, Asim B. Abdel-Mageed. Tumor associated microvesicles confer neoplastic transformation of patient derived adipose stem cells . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2612. doi:10.1158/1538-7445.AM2013-2612
Lipoprotein subclass and particle size differences in Afro-Caribbeans, African Americans, and white Americans: associations with hepatic lipase gene variation
Authors: Iva Miljkovic-Gacic, Clareann H. Bunker, Robert E. Ferrell, Candace M. Kammerer, Rhobert W. Evans, Alan L. Patrick, Lewis H. Kuller
Journal: Metabolism (2005)
Macrophage p53 Deficiency Leads to Enhanced Atherosclerosis in APOE*3-Leiden Transgenic Mice
Authors: Bart J.M. van Vlijmen, Gery Gerritsen, Arthur L. Franken, Lianne S.M. Boesten, Mark M. Kockx, Marion J. Gijbels, Michel P. Vierboom, Miranda van Eck, Bob van de Water, Theo J.C. van Berkel, Louis M. Havekes
Journal: Circulation Research (2001)

Cell proliferation and cell death (either necrosis or apoptosis) are key processes in the progression of atherosclerosis. The tumor suppressor gene p53 is an essential gene in cell proliferation and cell death and is upregulated in human atherosclerotic plaques, both in smooth muscle cells and in macrophages. In the present study, we investigated the importance of macrophage p53 in the progression of atherosclerosis using bone marrow transplantation in APOE*3-Leiden transgenic mice, an animal model for human-like atherosclerosis. APOE*3-Leiden mice were lethally irradiated and reconstituted with bone marrow derived from either p53-deficient (p53(-/-)) or control (p53(+/+)) donor mice. Reconstitution of mice with p53(-/-) bone marrow did not result in any hemopoietic abnormalities as compared with p53(+/+) transplanted mice. After 12 weeks on an atherogenic diet, APOE*3-Leiden mice reconstituted with p53(-/-) bone marrow showed a significant (P=0.006) 2.3-fold increase in total atherosclerotic lesion area as compared with mice reconstituted with p53(+/+) bone marrow. Although likely a secondary effect of the increased lesion area, p53(-/-) transplanted mice also showed significantly more lesion necrosis (necrotic index, 1.1+/-1.3 versus 0.2+/-0.7; P=0.04) and lesion macrophages (macrophage area, 79.9+/-40.0 versus 39.7+/-27.3x10(3) micrometer(2) per section; P=0.02). These observations coincided with a tendency toward decreased apoptosis (terminal deoxynucleotidyl transferase end-labeling [TUNEL]-positive nuclei going from 0.42+/-0.39 to 0.14+/-0.15%, P=0.071), whereas the number of proliferating cells (5'-bromo-2'-deoxyuridine-positive nuclei) was not affected (3.75+/-0.98 versus 4.77+/-2.30%; P=0.59). These studies indicate that macrophage p53 is important in suppressing the progression of atherosclerosis and identify a novel therapeutic target for regulating plaque stability.
Obesity and Albuminuria Among Adults With Type 2 Diabetes
Authors: Holly Kramer, David Reboussin, Alain G. Bertoni, Santica Marcovina, Edward Lipkin, Frank L. Greenway, Frederick L. Brancati
Journal: Diabetes Care (2009)

OBJECTIVE To determine the association between obesity measures and albuminuria in adults with type 2 diabetes. RESEARCH DESIGN AND METHODS In the Look AHEAD (Action for Health in Diabetes) Study, BMI and waist circumference were measured among 4,985 participants while total percent body fat was measured by whole-body DEXA scans among 1,351 participants. Odds of albuminuria by quartiles of BMI, waist circumference, and percent total body fat were calculated using logistic regression analysis while adjusting for covariates. RESULTS The highest quartile of BMI (odds ratio [OR] 1.72 [95% CI 1.40–2.11]) and waist circumference (OR 1.75 [95% CI 1.42–2.15]) was significantly associated with albuminuria compared with the lowest quartile after adjustment for covariates. No associations were noted between quartiles of percent total body fat and albuminuria in any model. CONCLUSIONS Increased BMI and abdominal obesity are associated with albuminuria in overweight and obese adults with type 2 diabetes.
A Phase II Study of PD-0325901, an Oral MEK Inhibitor, in Previously Treated Patients with Advanced Non–Small Cell Lung Cancer
Authors: Eric B. Haura, Alejandro D. Ricart, Timothy G. Larson, Philip J. Stella, Lyudmila Bazhenova, Vincent A. Miller, Roger B. Cohen, Peter D. Eisenberg, Paulina Selaru, Keith D. Wilner, Shirish M. Gadgeel
Journal: Clinical Cancer Research (2010)

To evaluate the efficacy of mitogen-activated protein kinase/extracellular signal-related kinase kinase inhibitor PD-0325901 in advanced non-small cell lung cancer patients who had experienced treatment failure after, or were refractory to, standard systemic therapy.This open-label, phase II study initially evaluated 15 mg PD-0325901 twice daily administered intermittently (3 weeks on/1 week off; schedule A). As this schedule was not well tolerated, a second schedule was introduced as follows: 5 days on/2 days off for 3 weeks, followed by 1 week off (schedule B). The primary end point was objective response.All patients had received prior systemic therapy (median of two regimens, including epidermal growth factor receptor inhibitors in 26%). Of 13 patients treated on schedule A, three discontinued due to adverse events (blurred vision, fatigue, and hallucinations, respectively). Twenty-one patients received schedule B. Main toxicities included diarrhea, fatigue, rash, vomiting, nausea, and reversible visual disturbances. Hematologic toxicity consisted mainly of mild-to-moderate anemia, without neutropenia. Chemistry abnormalities were rare. Mean (coefficient of variation) PD-0325901 trough plasma concentrations were 100 ng/mL (52%) and 173 ng/mL (73%) for schedules A and B, respectively, above the minimum target concentration established in preclinical studies (16.5 ng/mL). There were no objective responses. Seven patients had stable disease. Median (95% confidence interval) progression-free survival was 1.8 months (1.5-1.9) and overall survival was 7.8 months (4.5-13.9).PD-0325901 did not meet its primary efficacy end point. Future studies should focus on PD-0325901 schedule, rational combination strategies, and enrichment of patient selection based on mode of action.
Do nurses do it better?
Authors: S Rafferty
Journal: Thorax (2002)

Complexity is a fundamental attribute of life. Complex systems are made of parts that together perform functions that a single component, or subsets containing individual components, cannot. Examples of complex molecular systems include protein structures such as the F1Fo-ATPase, the ribosome, or the flagellar motor: each one of these structures requires most or all of its components to function properly. Given the ubiquity of complex systems in the biosphere, understanding the evolution of complexity is central to biology. At the molecular level, operons are a classic example of a complex system. An operon9s genes are co-transcribed under the control of a single promoter to a polycistronic mRNA molecule, and the operon9s gene products often form molecular complexes or metabolic pathways. With the large number of complete bacterial genomes available, we now have the opportunity to explore the evolution of these complex entities, by identifying possible intermediate states of operons. In this work, we developed a maximum parsimony algorithm to reconstruct ancestral operon states, and show a simple vertical evolution model of how operons may evolve from the individual component genes. We describe several ancestral states that are plausible functional intermediate forms leading to the full operon. We also offer Reconstruction of Ancestral Gene blocks Using Events or ROAGUE as a software tool for those interested in exploring gene block and operon evolution.
Absence of impaired lymphocyte transformation to Klebsiella spp. in ankylosing spondylitis.
Authors: T D Kinsella, C Lanteigne, M J Fritzler, R M Lewkonia
Journal: Annals of the Rheumatic Diseases (1984)

We have evaluated claims that impaired peripheral blood lymphocyte (PBL) transformation can occur with Klebsiella spp. in patients with ankylosing spondylitis (AS). PBL of four AS patients were cultured in vitro with autogenous faecal klebsiella, as were the PBL of age (+/- 3 years) and sex-matched pairs of 15-20 AS and normal controls cultured with heterogeneous AS-derived klebsiella and control bacterial isolates. Three of four AS patients responded to their own isolates, and no significant differences were found between the matched pairs in response to heterogeneous klebsiella isolates, including K21. Our studies did not show impaired PBL transformation with klebsiella in AS and therefore do not support claims of antigenic cross-reactivity between klebsiella and HLA-B27.
Protein Kinase D3 (PKD3) Contributes to Prostate Cancer Cell Growth and Survival Through a PKCε/PKD3 Pathway Downstream of Akt and ERK 1/2
Authors: Jun Chen, Fan Deng, Shivendra V. Singh, Qiming J. Wang
Journal: Cancer Research (2008)

Protein kinase D (PKD) is a family of novel diacylglycerol/phorbol ester targets that regulate many important cellular functions including cell growth and survival. We now provide experimental evidence to indicate that PKD3 contributes to prostate cancer cell growth and survival. Expression of PKD3 as well as PKD1 was significantly higher in human prostate tumors compared with normal tissues as revealed by immunohistochemistry. Moreover, PKD3 exhibited a marked increase in nuclear localization in tumor tissues, which correlated with tumor grade. Isoforms of PKD were differentially expressed and localized between normal and human prostate cancer cells. Increased protein expression and nuclear accumulation of PKD3 were observed in the more aggressive androgen-independent PC3 and DU145 cells compared with the less aggressive androgen-dependent LNCaP cells. Overexpression of wild-type PKD3 in LNCaP cells blocked phorbol 12-myristate 13-acetate (PMA)-induced apoptosis in association with inhibition of PMA-induced down-regulation of Akt activity, and prolonged extracellular signal-regulated kinase (ERK)1/2 activation. Overexpression of wild-type PKD3 also promoted S phase entry, whereas depletion of endogenous PKD3 resulted in G(0)-G(1) phase cell cycle arrest and inhibition of PC3 cell proliferation. In PC3 and DU145 cells, PKCepsilon regulated PKD3 kinase activity and nuclear localization. Moreover, ectopical expression of PKD3 increased, whereas depletion of endogenous PKD3 reduced basal Akt and ERK1/2 activities. Further analysis showed that up-regulation of Akt activity induced by PKD3 required phosphatidylinositol-3-OH kinase and p38. In summary, our data indicate that PKD3 contributes to growth and survival of prostate cancer cells and may represent a novel therapeutic target for prostate cancer.
Thyrotropin and Homologous Glycoprotein Hormone Receptors: Structural and Functional Aspects of Extracellular Signaling Mechanisms
Authors: Gunnar Kleinau, Gerd Krause
Journal: Endocrine Reviews (2009)

The TSH receptor (TSHR) together with the homologous lutropin/choriogonadotropin receptor and the follitropin receptor are glycoprotein hormone receptors (GPHRs). They constitute a subfamily of the rhodopsin-like G protein-coupled receptors with seven transmembrane helices. GPHRs and their corresponding hormones are pivotal proteins with respect to a variety of physiological functions. The identification and characterization of intra- and intermolecular signaling determinants as well as signaling mechanisms are prerequisites to gaining molecular insights into functions and (pathogenic) dysfunctions of GPHRs. Knowledge about activation mechanisms is fragmentary, and the specific aspects have still not been understood in their entirety. Therefore, here we critically review the data available for these receptors and bring together structural and functional findings with a focus on the important large extracellular portion of the TSHR. One main focus is the particular function of structural determinants in the initial steps of the activation such as: 1) hormone binding at the extracellular site; 2) hormone interaction at a second binding site in the hinge region; 3) signal regulation via sequence motifs in the hinge region; and 4) synergistic signal amplification by cooperative effects of the extracellular loops toward the transmembrane region. Comparison and consolidation of data from the homologous glycoprotein hormone receptors TSHR, follitropin receptor, and lutropin/choriogonadotropin receptor provide an overview of extracellular mechanisms of signal initiation, conduction, and regulation at the TSHR and homologous receptors. Finally, we address the issue of structural implications and suggest a refined scenario for the initial signaling process on GPHRs.
Allergens on desktop surfaces in preschools and elementary schools of urban children with asthma
Authors: W. Kanchongkittiphon, W. J. Sheehan, J. Friedlander, M. D. Chapman, E.‐M. King, K. Martirosyan, S. N. Baxi, P. Permaul, J. M. Gaffin, L. Kopel, A. Bailey, C. Fu, C. R. Petty, D. R. Gold, W. Phipatanakul
Journal: Allergy (2014)

Abstract Desktop dust has been studied as a source of food allergen, but not as a source of potential aeroallergen exposure. Thirty‐six wiped samples from desktop surfaces were collected from preschools and schools. Samples were analyzed for detectable levels of common aeroallergens including Alternaria, cockroach, dog, dust mite, cat, mouse, and rat allergens by immunoassay. Mouse allergen was the most prevalent, detectable in 97.2% of samples. Cat allergen was detectable in 80.6% of samples, and dog allergen was detectable in 77.8% of samples. Other allergens were not as prevalent. Mouse was the only allergen that was highly correlated with settled floor dust collected from the same rooms ( r = 0.721, P &lt; 0.001). This is the first study to detect aeroallergens on desktop surfaces by using moist wipes. Allergens for mouse, cat, and dog were highly detectable in wipes with mouse desktop surface levels correlating with levels in vacuumed floor dust.
Coronary artery bypass grafting on the beating heart: changing the paradigm
Authors: G J Murphy, G D Angelini
Journal: Journal of the Royal Society of Medicine (2004)

Over the past decade coronary artery bypass grafting (CABG) on the beating heart (off-pump or OPCAB) has become a standard procedure in many centres worldwide; however, the practice of OPCAB ranges from 0% to 100% of cases, even between surgeons operating in the same unit. This variation is the result of several interrelated factors, the most important of which is the question of graft patency. Some surgeons express concern about the quality of distal anastomoses performed on a moving field, and question the need to alter their practice from the perceived gold standard of conventional coronary artery surgery with cardiopulmonary bypass and cardioplegic arrest. This scepticism is self perpetuating, since a lack of familiarity reinforces the perception that OPCAB is technically too demanding or gives worse outcomes. Another major consequence is a paucity of adequate training in OPCAB techniques. In truth, the evidence to date indicates that OPCAB, when compared with conventional CABG, is associated with at least equivalent clinical outcome at lower cost.1-11 Furthermore, training in OPCAB techniques, as part of a structured programme, has been shown to be safe and successful.12,13 Existing evidence challenges the paradigm that conventional on-pump CABG represents the gold standard in surgical revascularization. This has important implications for the future practice of cardiac surgery. In particular, are current cardiothoracic training programmes in the UK and elsewhere capable of training the next generation of surgeons in OPCAB techniques?
Enhancement of Lung Tumor Formation in Mice by Dietary Butylated Hydroxy toluene: Dose-Time Relationships and Cell Kinetics&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: H R Witschi, C C Morse
Journal: JNCI Journal of the National Cancer Institute (1983)

Strain A/J mice given injections of 1,000 mg urethan/kg and fed for 12 weeks a diet containing 0.75% of butylated hydroxytoluene (BHT) had significantly more tumors per lung 4 or 9 months later than animals given urethan and fed a control diet. A 2-week exposure to dietary BHT (0.75%) was sufficient to significantly enhance tumor development, and the lowest effective BHT concentration was 0.1%, fed for 8 weeks. Tumor development was also enhanced in animals treated once with 3-methylcholanthrene, benzo[a]pyrene, or N-nitrosodimethylamine and, beginning 24 hours later, fed BHT for 8 weeks. Cell kinetic studies showed that BHT given in the diet produced increased proliferation of type II alveolar cells during the first 2 weeks and that initial cell proliferation was delayed in urethan-treated animals.
Adopting 3-Year Screening Intervals for Sight-Threatening Retinal Vascular Lesions in Type 2 Diabetic Subjects Without Retinopathy
Authors: Elisabet Agardh, Poya Tababat-Khani
Journal: Diabetes Care (2011)

To report the incidence of sight-threatening vascular lesions in type 2 diabetic subjects without retinopathy after adopting a 3-year interval screening program.In all, 1,691 type 2 diabetic subjects with no detectable retinopathy in two 50° red-free fundus photographs were scheduled for follow-up with photography 3 years later. Age at diabetes diagnosis was 60 ± 12 years, and known duration of diabetes was 6 ± 6 years. Treatment consisted of diet only (26%), oral agents (54%), and oral agents and/or insulin (20%). Glycated hemoglobin A(1c) was 6.4 ± 1.5%.Of the 1,322 subjects available for follow-up, 73% were still without retinopathy after 3 years, and 28% had developed mild or moderate retinopathy, but none developed severe nonproliferative or proliferative retinopathy. Macular edema requiring laser coagulation occurred in only one eye.Three-year retinal screening intervals can be recommended in subjects with mild type 2 diabetes and no retinopathy.