tbuckley/cabot-search huggingface dataset:
The Choice of Hemodialysis Membrane Affects Bisphenol A Levels in Blood
Authors: Enrique Bosch-Panadero, Sebastian Mas, Didier Sanchez-Ospina, Vanesa Camarero, Maria V. Pérez-Gómez, Isabel Saez-Calero, Pedro Abaigar, Alberto Ortiz, Jesus Egido, Emilio González-Parra
Journal: Journal of the American Society of Nephrology (2015)

Bisphenol A (BPA), a component of some dialysis membranes, accumulates in CKD. Observational studies have linked BPA exposure to kidney and cardiovascular injury in humans, and animal studies have described a causative link. Normal kidneys rapidly excrete BPA, but insufficient excretion may sensitize patients with CKD to adverse the effects of BPA. Using a crossover design, we studied the effect of dialysis with BPA-containing polysulfone or BPA-free polynephron dialyzers on BPA levels in 69 prevalent patients on hemodialysis: 28 patients started on polysulfone dialyzers and were switched to polynephron dialyzers; 41 patients started on polynephron dialyzers and were switched to polysulfone dialyzers. Results were grouped for analysis. Mean BPA levels increased after one hemodialysis session with polysulfone dialyzers but not with polynephron dialyzers. Chronic (3-month) use of polysulfone dialyzers did not significantly increase predialysis serum BPA levels, although a trend toward increase was detected (from 48.8±6.8 to 69.1±10.1 ng/ml). Chronic use of polynephron dialyzers reduced predialysis serum BPA (from 70.6±8.4 to 47.1±7.5 ng/ml, P &lt;0.05). Intracellular BPA in PBMCs increased after chronic hemodialysis with polysulfone dialyzers (from 0.039±0.002 to 0.043±0.001 ng/10 6 cells, P &lt;0.01), but decreased with polynephron dialyzers (from 0.045±0.001 to 0.036±0.001 ng/10 6 cells, P &lt;0.01). Furthermore, chronic hemodialysis with polysulfone dialyzers increased oxidative stress in PBMCs and inflammatory marker concentrations in circulation. In vitro , polysulfone membranes released significantly more BPA into the culture medium and induced more cytokine production in cultured PBMCs than did polynephron membranes. In conclusion, dialyzer BPA content may contribute to BPA burden in patients on hemodialysis.
Acceptance Reaction
Authors: AKIRA SHIMIZU, KAZUHIKO YAMADA, SHANE M. MEEHAN, DAVID H. SACHS, ROBERT B. COLVIN
Journal: Journal of the American Society of Nephrology (2000)

Inbred miniature swine that are treated for 12 d with a high dose of cyclosporin A develop tolerance to MHC class II matched, class I-mismatched renal allografts. The aim of this study was to clarify the intrarenal allograft events associated with the development of tolerance in this protocol. Morphologic and immunologic studies were performed in serial biopsies from accepting grafts after 12 d of cyclosporin A treatment (n = 4) and were compared with those from untreated control rejecting grafts (n = 4). In accepting grafts with stable function, a transient interstitial infiltrate developed. The cellular infiltrate had many similarities to that in rejecting grafts; both had T cells and macrophages, similar proportions of T-cell subsets, and a similar frequency of in situ nick end labeling (TUNEL)+ apoptotic infiltrating cells. However, the cellular infiltrate in the acceptance reaction was distinguished by less T-cell activation (interleukin-2 receptor+), less proliferation (proliferating cell nuclear antigen+) of infiltrating cells, and less graft cell apoptosis in arteries, tubules, glomeruli, and peritubular capillaries. Thereafter, the infiltrate in the accepting grafts progressively resolved with decreased cell proliferation, activation, and apoptotic graft parenchymal cell injury, but the high frequency of apoptosis persisted in graft-infiltrating cells. In parallel to the intragraft events, donor-specific unresponsiveness developed as assessed by cell-mediated cytotoxicity by blood mononuclear cells in vitro. In conclusion, the acceptance reaction in transplanted grafts is characterized by progressive resolution of T-cell proliferation and activation and of cell-mediated graft injury, as well as prolonged T-cell apoptosis. These intragraft events suggest that both T-cell anergy and T-cell deletion occur in the graft during the development of tolerance. Some of the described immunopathologic findings (activation, proliferation, apoptosis) may be useful in distinguishing acceptance from rejection, as well as in predicting later graft acceptance in tolerance induction protocols.
Sirt7 Contributes to Myocardial Tissue Repair by Maintaining Transforming Growth Factor-β Signaling Pathway
Authors: Satoshi Araki, Yasuhiro Izumiya, Taku Rokutanda, Alessandro Ianni, Shinsuke Hanatani, Yuichi Kimura, Yoshiro Onoue, Takafumi Senokuchi, Tatsuya Yoshizawa, Osamu Yasuda, Norimichi Koitabashi, Masahiko Kurabayashi, Thomas Braun, Eva Bober, Kazuya Yamagata, Hisao Ogawa
Journal: Circulation (2015)

Sirt7, 1 of the 7 members of the mammalian sirtuin family, promotes oncogenic transformation. Tumor growth and metastasis require fibrotic and angiogenic responses. Here, we investigated the role of Sirt7 in cardiovascular tissue repair process.In wild-type mice, Sirt7 expression increased in response to acute cardiovascular injury, including myocardial infarction and hind-limb ischemia, particularly at the active wound healing site. Compared with wild-type mice, homozygous Sirt7-deficient (Sirt7(-/-)) mice showed susceptibility to cardiac rupture after myocardial infarction, delayed blood flow recovery after hind-limb ischemia, and impaired wound healing after skin injury. Histological analysis showed reduced fibrosis, fibroblast differentiation, and inflammatory cell infiltration in the border zone of infarction in Sirt7(-/-) mice. In vitro, Sirt7(-/-) mouse-derived or Sirt7 siRNA-treated cardiac fibroblasts showed reduced transforming growth factor-β signal activation and low expression levels of fibrosis-related genes compared with wild-type mice-derived or control siRNA-treated cells. These changes were accompanied by reduction in transforming growth factor receptor I protein. Loss of Sirt7 activated autophagy in cardiac fibroblasts. Transforming growth factor-β receptor I downregulation induced by loss of Sirt7 was blocked by autophagy inhibitor, and interaction of Sirt7 with protein interacting with protein kinase-Cα was involved in this process.Sirt7 maintains transforming growth factor receptor I by modulating autophagy and is involved in the tissue repair process.
A Plasmonic Gold Nanostar Theranostic Probe for <i>In Vivo</i> Tumor Imaging and Photothermal Therapy
Authors: Yang Liu, Jeffrey R. Ashton, Everett J. Moding, Hsiangkuo Yuan, Janna K. Register, Andrew M. Fales, Jaeyeon Choi, Melodi J. Whitley, Xiaoguang Zhao, Yi Qi, Yan Ma, Ganesan Vaidyanathan, Michael R. Zalutsky, David G. Kirsch, Cristian T. Badea, Tuan Vo-Dinh
Journal: Theranostics (2015)

Nanomedicine has attracted increasing attention in recent years, because it offers great promise to provide personalized diagnostics and therapy with improved treatment efficacy and specificity.In this study, we developed a gold nanostar (GNS) probe for multi-modality theranostics including surface-enhanced Raman scattering (SERS) detection, x-ray computed tomography (CT), two-photon luminescence (TPL) imaging, and photothermal therapy (PTT).We performed radiolabeling, as well as CT and optical imaging, to investigate the GNS probe's biodistribution and intratumoral uptake at both macroscopic and microscopic scales.We also characterized the performance of the GNS nanoprobe for in vitro photothermal heating and in vivo photothermal ablation of primary sarcomas in mice.The results showed that 30-nm GNS have higher tumor uptake, as well as deeper penetration into tumor interstitial space compared to 60-nm GNS.In addition, we found that a higher injection dose of GNS can increase the percentage of tumor uptake.We also demonstrated the GNS probe's superior photothermal conversion efficiency with a highly concentrated heating effect due to a tip-enhanced plasmonic effect.In vivo photothermal therapy with a near-infrared (NIR) laser under the maximum permissible exposure (MPE) led to ablation of aggressive tumors containing GNS, but had no effect in the absence of GNS.This multifunctional GNS probe has the potential to be used for in vivo biosensing, preoperative CT imaging, intraoperative detection with optical methods (SERS and TPL), as well as image-guided photothermal therapy.
Pasteurella Septica Infections In Humans
Authors: B FREIGANG, G B ELLIOTT
Journal: JAMA (1963)

Five instances of infection by Pasteurella septica, an organism which closely resembles H. influenzae on methods of presumptive bacteriology, are reported from an acute treatment general hospital practice over a period of three months. This infection decidedly outnumbers those caused by other Pasteurella species in North America. The organism is apt to be identified as H. influenzae, Friedlander's bacillus or Mima polymorpha. Unlike these, it shows extreme sensitivity to penicillin, sometimes combined with resistance to antibiotics that inhibit or kill these other organisms.While in the past Pasteurella septica infection was considered to be characterized by persistent local infection following domestic animal scratches or bites, it is clear that it is more often found in cases of respiratory tract infection and peripheral septic disease. In three of the five cases reported, exposure to animals was the source of infection.Because mixed infection with confusingly similar organisms may occur, lack of awareness of extreme penicillin sensitivity of Pasteurella septica may account for persistent failure of antibiotic therapy.
Abstract 638: Modulation of antibody-dependent cytokine release using Fc engineering
Authors: Michelle Kinder, Allison Greenplate, William Strohl, Robert Jordan, Randall Brezski
Journal: Cancer Research (2015)

Abstract Antibodies can elicit multiple functions through its Fc region, including cell-killing through antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxity (CDC) and antibody-dependent cellular phagocytosis (ADCP). In addition to the cell-killing functions, antibodies also mediate antibody-dependent cytokine release (ADCR). In this study, we demonstrate that ADCR is regulated differentially in PBMC and macrophages. ADCR is FcγRIII-dependent in PBMC and mediated by NK cells. In contrast, ADCR in macrophages is FcγRI-dependent. In PBMC, ADCR is characterized by expression of primarily pro-inflammatory cytokines including IFN-γ, IL-1α, IL-1ß, TNF-α. Meanwhile in macrophages, ADCR results in a mixture of the anti-inflammatory cytokine IL-10 and pro-inflammatory cytokines including IFN-γ, IL-1α, IL-1ß, TNF-α, and RANTES. Using an Fc engineering approach, we generated antibody variants lacking FcγRI binding while maintaining binding to FcγRIIa and FcγRIII. These variants retain ADCC and ADCR in PBMC, but modulate ADCP without eliciting cytokine release in macrophages, separating the two processes. Ultimately, a better understanding of how cytokine release is regulated by antibodies and of strategies to modulate cytokine release through Fc engineering could be used to influence immune cell fate decisions in vivo. Citation Format: Michelle Kinder, Allison Greenplate, William Strohl, Robert Jordan, Randall Brezski. Modulation of antibody-dependent cytokine release using Fc engineering. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 638. doi:10.1158/1538-7445.AM2015-638
Stromal Fibroblasts Induce CCL20 through IL6/C/EBPβ to Support the Recruitment of Th17 Cells during Cervical Cancer Progression
Authors: Barbara Walch-Rückheim, Russalina Mavrova, Melanie Henning, Benjamin Vicinus, Yoo-Jin Kim, Rainer Maria Bohle, Ingolf Juhasz-Böss, Erich-Franz Solomayer, Sigrun Smola
Journal: Cancer Research (2015)

Abstract Cervical cancer is a consequence of persistent infection with human papillomaviruses (HPV). Progression to malignancy is linked to an inflammatory microenvironment comprising T-helper-17 (Th17) cells, a T-cell subset with protumorigenic properties. Neoplastic cells express only low endogenous levels of the Th17 chemoattractant CCL20, and therefore, it is unclear how Th17 cells are recruited to the cervical cancer tissue. In this study, we demonstrate that CCL20 was predominantly expressed in the stroma of cervical squamous cell carcinomas in situ. This correlated with stromal infiltration of CD4+/IL17+ cells and with advancing International Federation of Gynecology and Obstetrics (FIGO) stage. Furthermore, we show that cervical cancer cells instructed primary cervical fibroblasts to produce high levels of CCL20 and to attract CD4/IL17/CCR6-positive cells, generated in vitro, in a CCL20/CCR6-dependent manner. Further mechanistic investigations identified cervical cancer cell–derived IL6 as an important mediator of paracrine CCL20 induction at the promoter, mRNA, and protein level in fibroblasts. CCL20 was upregulated through the recently described CCAAT/enhancer-binding protein β (C/EBPβ) pathway as shown with a dominant-negative version of C/EBPβ and through siRNA-mediated knockdown. In summary, our study defines a novel molecular mechanism by which cervical neoplastic cells shape their local microenvironment by instructing fibroblasts to support Th17 cell infiltration in a paracrine IL6/C/EBPβ-dependent manner. Th17 cells may in turn maintain chronic inflammation within high-grade cervical lesions to further promote cancer progression. Cancer Res; 75(24); 5248–59. ©2015 AACR.
Recent Applications of Hidden Markov Models in Computational Biology
Authors: Khar Heng Choo, Joo Chuan Tong, Louxin Zhang
Journal: Genomics Proteomics & Bioinformatics (2004)

Abstract This paper examines recent developments and applications of Hidden Markov Models (HMMs) to various problems in computational biology, including multiple sequence alignment, homology detection, protein sequences classification, and genomic annotation.
Prehospital Epinephrine Use and Survival Among Patients With Out-of-Hospital Cardiac Arrest
Authors: Akihito Hagihara, Manabu Hasegawa, Takeru Abe, Takashi Nagata, Yoshifumi Wakata, Shogo Miyazaki
Journal: JAMA (2012)

respectively, were 805 (5.4%), 205 (1.4%), and 211 (1.4%) with epinephrine and 18906 (4.7%), 8903 (2.2%), and 8831 (2.2%) without epinephrine (all P.001). Correspondingnumbersinpropensity-matchedpatientswere687(5.1%),173(1.3%),and178(1.3%) with epinephrine and 944 (7.0%), 413 (3.1%), and 410 (3.1%) without epinephrine (all P.001). In all patients, a positive association was observed between prehospital epinephrine and return of spontaneous circulation before hospital arrival (adjusted odds ratio [OR], 2.36; 95% CI, 2.22-2.50; P.001). In propensity-matched patients, a positive association was also observed (adjusted OR, 2.51; 95% CI, 2.24-2.80; P.001). In contrast, among all patients, negative associations were observed between prehospital epinephrine and long-term outcome measures (adjusted ORs: 1-month survival, 0.46 [95% CI, 0.42-0.51]; CPC 1-2, 0.31 [95% CI, 0.26-0.36]; and OPC 1-2, 0.32 [95% CI, 0.270.38]; all P.001). Similar negative associations were observed among propensitymatched patients (adjusted ORs: 1-month survival, 0.54 [95% CI, 0.43-0.68]; CPC 1-2, 0.21 [95% CI, 0.10-0.44]; and OPC 1-2, 0.23 [95% CI, 0.11-0.45]; all P.001). Conclusion Among patients with OHCA in Japan, use of prehospital epinephrine was significantly associated with increased chance of return of spontaneous circulation before hospital arrival but decreased chance of survival and good functional outcomes 1 month after the event.
High-risk prostate cancer treated with pelvic radiotherapy and 36 versus 18 months of androgen blockade: Results of a phase III randomized study.
Authors: Abdenour Nabid, Nathalie Carrier, André-Guy Martin, Jean-Paul Bahary, Luis Souhami, Marie Duclos, François Vincent, Sylvie Vass, Boris Bahoric, Robert Archambault, Céline Lemaire
Journal: Journal of Clinical Oncology (2013)

3 Background: Radiotherapy (RT) and long term androgen blockade (AB) is standard treatment for patients with high risk prostate cancer. However, the optimal duration of AB is not yet defined. The purpose of this randomized study was to compare outcomes between 36 vs. 18 months of AB in high risk prostate cancer treated with RT (PCS IV trial, Clinical Trials.gov, #NCT00223171). Methods: PCS IV randomized patients with node negative high risk prostate cancer (T3-4, PSA &gt;20 ng/ml or Gleason score &gt;7), to pelvic RT (whole pelvis 44 Gy/4 ½ weeks, prostate 70 Gy/7 weeks) and 36 (arm 1) vs. 18 months (arm 2) of AB (neo adjuvant, concomitant, adjuvant). AB consisted of bicalutamide 50 mg for one month plus goserelin 10.8 mg every three months for 36 vs. 18 months. Overall survival was the primary end point. Overall and cancer specific survival rates were compared between arms with Kaplan-Meier log rank test and Cox regression. Results: From October 2000 to January 2008, 310 patients were randomized to arm 1 and 320 to arm 2. Patients’ characteristics were well balanced between the two arms (median age 71 years, median PSA 16 ng/ml, median Gleason score 8). Most patients had T2-3 disease. At a median follow-up of 77 months, 71/310 patients (22.9%) in arm 1 and 76/320 (23.8%) in arm 2 had died (p=0.802). Overall, 116 patients died of causes other than prostate cancer. Overall and cancer specific survival hazard ratios were 1.15 (0.83-1.59), p=0.398 and 1.13 (0.61-2.08), p=0.153, respectively. 5 year overall and disease specific survival rates were 92.1% (89.1-95.1) vs. 86.8% (83.0-90.6), p=0.052 and 97.6% (95.9-99.4) vs. 96.4% (94.2-98.6), p=0.473 and 10 year overall and disease specific survival rates were 63.6% (55.7-71.5) vs. 63.2% (54.7-71.7), p=0.429 and 87.2% (81.0-93.3) vs. 87.2% (80.9-93.6), p=0.838 for arm 1 and arm 2, respectively. There were no significant differences in the rates of biochemical, regional or distant failure between arms. Conclusions: Our study shows that long term AB can be safely reduced from 36 to 18 months without compromising outcomes. Analysis of treatment impact on quality of life is now under review. Source of Funding: AstraZeneca Pharmaceuticals Grant. Clinical trial information: Clinical Trials.gov, #NCT00223171.
Endovascular Therapy for Ischemic Stroke
Authors: Bryan M Bishop
Journal: New England Journal of Medicine (2015)

To the Editor: In their report on the Extending the Time for Thrombolysis in Emergency Neurological Deficits - Intra-Arterial (EXTEND-IA) trial, Campbell et al. (March 12 issue)(1) suggest that in MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands), local investigators might have selected patients on the basis of findings on computed tomographic (CT) perfusion imaging, although such selection was not specified in the protocol.(2),(3) We compared the effect of endovascular therapy in patients with and in those without CT perfusion data. In 166 patients without such data, the adjusted common odds . .
Slow walking speed may be early sign of Alzheimer’s in older people, study finds
Authors: Susan Mayor
Journal: BMJ (2015)

Slow walking speed in older people is associated with higher levels of amyloid β in several areas of the brain in those who are at high risk but not yet showing symptoms of Alzheimer’s disease, a study has found,1 showing that slower gait speed may be an early sign of the condition.

The study, published in Neurology , examined cross sectional associations between levels of brain amyloid β, measured by positron emission tomography (PET), and gait speed in 128 elderly people …
Androgens Enhance Male Urinary Tract Infection Severity in a New Model
Authors: Patrick D. Olson, Keith A. Hruska, David A. Hunstad
Journal: Journal of the American Society of Nephrology (2015)

Urinary tract infections (UTIs) occur predominantly in females but also affect substantial male patient populations; indeed, morbidity in complicated UTI is higher in males. Because of technical obstacles, preclinical modeling of UTI in male mice has been limited. We devised a minimally invasive surgical bladder inoculation technique that yields reproducible upper and lower UTI in both male and female mice, enabling studies of sex differences in these infections. Acute uropathogenic Escherichia coli (UPEC) cystitis in C57BL/6 and C3H/HeN males recapitulated the intracellular bacterial community pathway previously shown in females. However, surgically infected females of these strains exhibited more robust bladder cytokine responses and more efficient UPEC control than males. Compared with females, C3H/HeN males displayed a striking predilection for chronic cystitis, manifesting as persistent bacteriuria, high-titer bladder bacterial burdens, and chronic inflammation. Furthermore, males developed more severe pyelonephritis and 100% penetrant renal abscess (a complication that is rare in female mice). These phenotypes were sharply abrogated after castration but restored with exogenous testosterone, suggesting that male susceptibility to UTI is strongly influenced by androgen exposure. These data substantiate the long-standing presumption that anatomic differences in urogenital anatomy confer protection from UTI in males; however, as clinically observed, male sex associated with more severe UTI once these traditional anatomic barriers were bypassed. This study introduces a highly tractable preclinical model for interrogating sex differences in UTI susceptibility and pathogenesis, and illuminates an interplay between host sex and UTI that is more complex than previously appreciated.