tbuckley/cabot-search huggingface dataset:
Diabetes Is the Strongest Risk Factor for Lower-Extremity Amputation in New Hemodialysis Patients
Authors: Rebecca A. Speckman, Diane L. Frankenfield, Sheila H. Roman, Paul W. Eggers, Marjorie R. Bedinger, Michael V. Rocco, William M. McClellan
Journal: Diabetes Care (2004)

End-stage renal disease (ESRD) patients, especially those with diabetes, have an increased risk of nontraumatic lower-extremity amputation (LEA). The present study aims to examine the association of demographic and clinical variables with the risk of hospitalization for LEA among incident hemodialysis patients.The study population consisted of incident hemodialysis patients from the study years 1996-1999 of the ESRD Core Indicator/Clinical Performance Measures (CPM) Project. Cox proportional hazard modeling was used to identify factors associated with LEA.Four percent (116 of 3,272) of noncensored incident patients had an LEA during the 12-month follow-up period. Factors associated with LEA included diabetes as the cause of ESRD or preexisting comorbidity (hazard ratio 6.4, 95% CI 3.4-12.0), cardiovascular comorbidity (1.8, 1.2-2.8), hemodialysis inadequacy (urea reduction ratio [URR] <58.5% (1.9, 1.1-3.3), and lower serum albumin level (1.6, 1.1-2.3). Among patients with diabetes, hemodialysis inadequacy and cardiovascular comorbidity were risk factors for LEA (2.6, 1.4-4.8, and 1.7, 1.1-2.6, respectively).These data suggest that diabetes is a potent risk factor for LEA in new hemodialysis patients. In ESRD patients with diabetes, a multipronged approach may reduce the rate of LEA. Potentially beneficial strategies include adherence to hemodialysis adequacy guidelines, aggressive treatment of cardiovascular comorbidities, and the utilization of LEA prevention strategies recommended for the general population of patients with diabetes.
Interleukin-12 primes human CD4 and CD8 T cell clones for high production of both interferon-gamma and interleukin-10.
Authors: F Gerosa, C Paganin, D Peritt, F Paiola, M T Scupoli, M Aste-Amezaga, I Frank, G Trinchieri
Journal: The Journal of Experimental Medicine (1996)

Interleukin-12 (IL-12) induces differentiation of T helper 1 (Th1) cells, primarily through its ability to prime T cells for high interferon-gamma (IFN-gamma) production. We now report that the presence of IL-12 during the first several days of in vitro clonal expansion in limiting dilution cultures of polyclonally stimulated human peripheral blood CD4+ and CD8+ T cells also induces stable priming for high IL-10 production. This effect was demonstrated with T cells from both healthy donors and HIV+ patients. Priming for IL-4 production, which requires IL-4, was maximum in cultures containing both IL-12 and IL-4. IL-4 modestly inhibited the IL-12-induced priming for IFN-gamma, but almost completely suppressed the priming for IL-10 production. A proportion of the clones generated from memory CD45RO+ cells, but not those generated from naive CD45RO- CD4+ T cells, produced some combinations of IFN-gamma, IL-10, and IL-4 even in the absence of IL-12 and IL-4, suggesting in vivo cytokine priming; virtually all CD4+ clones generated from either CD45RO(-) or (+) cells, however, produced high levels of both IFN-gamma and IL-10 when IL-12 was present during expansion. These results indicate that each Th1-type (IFN-gamma) and Th2-type (IL-4 and IL-10) cytokine gene is independently regulated in human T cells and that the dichotomy between T cells with the cytokine production pattern of Th1 and Th2 cells is not due to a direct differentiation-inducing effect of immunoregulatory cytokines, but rather to secondary selective mechanisms. Particular combinations of cytokines induce a predominant generation of T cell clones with anomalous patterns of cytokine production (e.g., IFN-gamma and IL-4 or IFN-gamma and IL-10) that can also be found in a proportion of fresh peripheral blood T cells with "memory" phenotype or clones generated from them and that may identify novel Th subsets with immunoregulatory functions.
ABCC6 Is a Basolateral Plasma Membrane Protein
Authors: Viola Pomozi, Olivier Le Saux, Christopher Brampton, Ailea Apana, Attila Iliás, Flóra Szeri, Ludovic Martin, Katalin Monostory, Sándor Paku, Balázs Sarkadi, Gergely Szakács, András Váradi
Journal: Circulation Research (2013)

ABCC6 plays a crucial role in ectopic calcification; mutations of the gene cause pseudoxanthoma elasticum and general arterial calcification of infancy. To elucidate the role of ABCC6 in cellular physiology and disease, it is crucial to establish the exact subcellular localization of the native ABCC6 protein.In a recent article in Circulation Research, ABCC6 was reported to localize to the mitochondria-associated membrane and not the plasma membrane. As the suggested mitochondrial localization is inconsistent with published data and the presumed role of ABCC6, we performed experiments to determine the cellular localization of ABCC6 in its physiological environment.We performed immunofluorescent labeling of frozen mouse and human liver sections, as well as primary hepatocytes. We used several different antibodies recognizing human and mouse ABCC6. Our results unequivocally show that ABCC6 is in the basolateral membrane of hepatocytes and is not associated with the mitochondria, mitochondria-associated membrane, or the endoplasmic reticulum.Our findings support the model that ABCC6 is in the basolateral membrane, mediating the sinusoidal efflux of a metabolite from the hepatocytes to systemic circulation.
Elevated sphingosine-1-phosphate promotes sickling and sickle cell disease progression
Authors: Yujin Zhang, Vladimir Berka, Anren Song, Kaiqi Sun, Wei Wang, Weiru Zhang, Chen Ning, Chonghua Li, Qibo Zhang, Mikhail Bogdanov, Danny C. Alexander, Michael V. Milburn, Mostafa H. Ahmed, Han Lin, Modupe Idowu, Jun Zhang, Gregory J. Kato, Osheiza Y. Abdulmalik, Wenzheng Zhang, William Dowhan, Rodney E. Kellems, Pumin Zhang, Jianping Jin, Martin Safo, Ah-Lim Tsai, Harinder S. Juneja, Yang Xia
Journal: Journal of Clinical Investigation (2014)

Sphingosine-1-phosphate (S1P) is a bioactive lipid that regulates multicellular functions through interactions with its receptors on cell surfaces. S1P is enriched and stored in erythrocytes; however, it is not clear whether alterations in S1P are involved in the prevalent and debilitating hemolytic disorder sickle cell disease (SCD). Here, using metabolomic screening, we found that S1P is highly elevated in the blood of mice and humans with SCD. In murine models of SCD, we demonstrated that elevated erythrocyte sphingosine kinase 1 (SPHK1) underlies sickling and disease progression by increasing S1P levels in the blood. Additionally, we observed elevated SPHK1 activity in erythrocytes and increased S1P in blood collected from patients with SCD and demonstrated a direct impact of elevated SPHK1-mediated production of S1P on sickling that was independent of S1P receptor activation in isolated erythrocytes. Together, our findings provide insights into erythrocyte pathophysiology, revealing that a SPHK1-mediated elevation of S1P contributes to sickling and promotes disease progression, and highlight potential therapeutic opportunities for SCD.
Yersinia enterocolitica enteritis in children
Authors: W. J. Rodriquez
Journal: JAMA (1979)

Five patients were admitted to Children's Hospital National Medical Center with manifestations of<i>Yersinia enterocolitica</i>infections. Four of five had primarily enteric illness, while the fifth had associated ocular and joint involvements. In three of five cases, the disease was self-limiting. Two of the patients (No. 1 and 2) may have had their disease improved by antibiotic therapy. Increased alertness to the potential of<i>Y enterocolitica</i>to cause a variety of syndromes is necessary to make an accurate bacteriologic diagnosis and to expedite medical treatment. (<i>JAMA</i>242:1978-1980, 1979)
Abstract 4785: miR-125b targets erythropoietin and its receptor and their expression correlates with metastatic potential and ERBB2/HER2 expression
Authors: Manuela Ferracin, Cristian Bassi, Massimo Pedriali, Sara Pagotto, Lucilla D'Abundo, Barbara Zagatti, Stefano Volpato, Patrizia Querzoli, Massimo Negrini
Journal: Cancer Research (2014)

Abstract Background: The microRNA 125b is a double-faced gene expression regulator described both as a tumor suppressor gene (in solid tumors) and an oncogene (in hematologic malignancies). In human breast cancer, it is one of the most down-regulated miRNAs and is able to modulate ERBB2/3 expression. Here, we investigated its targets in breast cancer cell lines after miRNA-mimic transfection. We examined the interactions of the validated targets with ERBB2 oncogene and the correlation of miR-125b expression with clinical variables. Methods: MiR-125b possible targets were identified after transfecting a miRNA-mimic in MCF7 cell line and analyzing gene expression modifications with Agilent microarrays and Sylamer bioinformatic tool. Erythropoietin (EPO) and its receptor (EPOR) were validated as targets of miR-125b by luciferase assay and their expression was assessed by RT-qPCR in 42 breast cancers and 13 normal samples. The molecular talk between EPOR and ERBB2 transcripts, through miR-125b, was explored transfecting MDA-MD-453 and MDA-MB-157 with ERBB2 RNA and using RT-qPCR. Results: We identified a panel of genes down-regulated after miR-125b transfection and putative targets of miR-125b. Among them, we validated erythropoietin (EPO) and its receptor (EPOR) - frequently overexpressed in breast cancer - as true targets of miR-125b. Moreover, we explored possible correlations with clinical variables and we found a down-regulation of miR-125b in metastatic breast cancers and a significant positive correlation between EPOR and ERBB2/HER2 levels, that are both targets of miR-125b and function as competing endogenous RNAs (ceRNAs). Conclusions: Taken together our results show a mechanism for EPO/EPOR and ERBB2 co-regulation in breast cancer and confirm the importance of miR-125b in controlling clinically-relevant cancer features. Citation Format: Manuela Ferracin, Cristian Bassi, Massimo Pedriali, Sara Pagotto, Lucilla D'Abundo, Barbara Zagatti, Stefano Volpato, Patrizia Querzoli, Massimo Negrini. miR-125b targets erythropoietin and its receptor and their expression correlates with metastatic potential and ERBB2/HER2 expression. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4785. doi:10.1158/1538-7445.AM2014-4785
Methotrexate for Ocular Inflammatory Diseases
Authors: Sapna Gangaputra, Craig W. Newcomb, Teresa L. Liesegang, R. Oktay Kaçmaz, Douglas A. Jabs, Grace A. Levy-Clarke, Robert B. Nussenblatt, James T. Rosenbaum, Eric B. Suhler, Jennifer E. Thorne
Journal: Ophthalmology (2009)
High-Affinity Arginine Transport of Bovine Aortic Endothelial Cells Is Impaired by Lysophosphatidylcholine
Authors: Ken-ichiro Kikuta, Tatsuya Sawamura, Soichi Miwa, Nobuo Hashimoto, Tomoh Masaki
Journal: Circulation Research (1998)

Abstract —The mechanisms of endothelial dysfunction characterized by the impaired nitric oxide (NO) release have not yet been clarified. Because the phenomenon is mimicked in vitro by the application of oxidized LDL and its major lipid constituent, lysophosphatidylcholine (LPC), we analyzed their effects on the arginine-NO system, especially on the arginine transport system. LPC inhibited NO release induced by ADP in cultured bovine aortic endothelial cells. The inhibition was attenuated by the excess amount of extracellular arginine. LPC was found to inhibit the arginine transport in bovine aortic endothelial cells, which is mediated by high- and low-affinity components. LPC predominantly impaired the high-affinity component. In the presence of a high concentration of arginine, LPC showed apparently no inhibition of arginine transport, because the low-affinity transporter compensated for the activity. Taken together, the impairment of the high-affinity transport system might account for the inhibition of NO release by LPC. LPC also inhibited arginine transport in the intima of intact bovine aorta. Furthermore, LPC inhibited the activity of the high-affinity arginine transporter in endothelial cells, in the cationic amino acid transporter-1 expressed in COS-7 cells. The activity of cationic amino acid transporter-1 might be important for the prevention of endothelial dysfunction.
Phase II Trial of 17-Allylamino-17-Demethoxygeldanamycin in Patients with Metastatic Melanoma
Authors: David B. Solit, Iman Osman, David Polsky, Katherine S. Panageas, Adil Daud, James S. Goydos, Jerrold Teitcher, Jedd D. Wolchok, F. Joseph Germino, Susan E. Krown, Daniel Coit, Neal Rosen, Paul B. Chapman
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Activation of the mitogen-activated protein kinase (MAPK) pathway and the phosphatidylinositol 3-kinase/AKT pathway seems to be critical for melanoma proliferation. Components of these pathways are client proteins of heat-shock protein 90 (hsp90), suggesting that inhibition of hsp90 could have significant antimelanoma effects. We conducted a phase II trial using the hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) in melanoma patients. The primary end points were clinical responses and whether treatment inhibited MAPK pathway activity. Experimental Design: Melanoma patients with measurable disease were stratified on the basis of whether or not their tumor harbored a V600E BRAF mutation. The hsp90 inhibitor 17-AAG was administered i.v. once weekly ×6 weeks at 450 mg/m2. Tumor biopsies were obtained pretreatment and 18 to 50 hours after the first dose of 17-AAG, and were snap-frozen. Results: Fifteen evaluable patients were treated; nine had BRAF mutations and six were wild-type. No objective responses were observed. Western blot analysis of tumor biopsies showed an increase in hsp70 and a decrease in cyclin D1 expression in the posttreatment biopsies but no significant effect on RAF kinases or phospho–extracellular signal-regulated kinase expression. Plasma analyzed by mutant-specific PCR for V600E BRAF showed 86% sensitivity and 67% specificity in predicting tumor DNA sequencing results. Conclusions: At this dose and schedule of 17-AAG, the effects of 17-AAG on RAF kinase expression were short-lived, and no objective antimelanoma responses were seen. Future trials in melanoma should focus on a more potent hsp90 inhibitor or a formulation that can be administered chronically for a more prolonged suppression of the MAPK pathway.
Use of broad-spectrum antibiotics.
Authors: M P Jevons
Journal: BMJ (1970)

Adjuvants to L-dopa for Parkinsonism SIR,-Notwithstanding the generally satisfactory response of Parkinsonian patients to L-dopa, undesirable side-effects and the high cost of the drug have led to attempts to reduce dosage with the aid of other agents.Success in this field has been reported using dopa-decarboxylase inhibitors,' the present moment the best method is to screen all patients "at risk" with the ratemeter, and to institute treatment at the proper time.-Weare, etc.,
Cecil Thompson Buchanan Adams Elisabeth Bride Carnegie Dickson John Robert Pelham Gibbons David Stoakley Hinson George Downes McDowell Frederic ("Eric") Guy Neild Louis Falconer Smith John Turner Spare Jessie Vivien Mary Walls (nee Robb) John Whyte Rodney Finlayson
Authors: B. Nicholl, D. A Craigmile, J. McGuigan, R. Nunn, B. Dale, G H Neild, J. F. Smith, T. Spare, E W Walls, T L Turner, J P McClure
Journal: BMJ (1999)

He served in the Royal Air Force during the second world war with postings as squadron leader in India and Africa.After the war Dr Adams worked with the newly formed Northern Ireland Tuberculosis Authority and was responsible for the service in several towns.At the time there were over 14 000 people with tuberculosis out of a population of about 1.3 million.The authority's report was published in 1959 when it was clear that the task to control the disease had been accomplished.Dr Adams
Advances in counselling and surveillance of patients at risk for pancreatic cancer
Authors: R. E Brand, M. M Lerch, W. S Rubinstein, J. P Neoptolemos, D. C Whitcomb, R. H Hruban, T. A Brentnall, H. T Lynch, M. I Canto
Journal: Gut (2007)

Even with significant advances in imaging and our understanding of pancreatic cancer genetics, the survival rates for pancreatic cancer remain quite dismal. Although still at an early stage, there are efforts in place to develop surveillance and prevention strategies for people at high risk for pancreatic cancer. This comprehensive review article summarises the predispositions that put people at a high risk of developing pancreatic cancer and the current status in the counselling and surveillance of these people using not only available medical literature, but also incorporating international expert opinion.
Implementing an exercise-training programme to prevent lower-limb injuries: considerations for the development of a randomised controlled trial intervention delivery plan
Authors: Caroline F Finch, Peta White, Dara Twomey, Shahid Ullah
Journal: British Journal of Sports Medicine (2011)

To identify important considerations for the delivery of an exercise training intervention in a randomised controlled trial to maximise subsequent participation in that randomised controlled trial and intervention uptake.A cross-sectional survey, with a theoretical basis derived from the Health Belief Model (HBM) and the Reach, Efficacy/Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework.374 male senior Australian Football players, aged 17-38 years.Beliefs about lower-limb injury causation/prevention, and the relative value of exercise training for performance and injury prevention. The data are interpreted within HBM constructs and implications for subsequent intervention implementation considered within the RE-AIM framework. Ordinal logistic regression compared belief scores across player characteristics.74.4% of players agreed that doing specific exercises during training would reduce their risk of lower-limb injury and would be willing to undertake them. However, 64.1% agreed that training should focus more on improving game performance than injury prevention. Younger players (both in terms of age and playing experience) generally had more positive views. Players were most supportive of kicking (98.9%) and ball-handling (97.0%) skills for performance and warm-up runs and cool-downs (both 91.5%) for injury prevention. Fewer than three-quarters of all players believed that balance (69.2%), landing (71.3%) or cutting/stepping (72.8) training had injury-prevention benefits.Delivery of future exercise training programmes for injury prevention aimed at these players should be implemented as part of routine football activities and integrated with those as standard practice, as a means of associating them with training benefits for this sport.
Effects of Metformin and Rosiglitazone Monotherapy on Insulin-Mediated Hepatic Glucose Uptake and Their Relation to Visceral Fat in Type 2 Diabetes
Authors: Patricia Iozzo, Kirsti Hallsten, Vesa Oikonen, Kirsi A. Virtanen, Riitta Parkkola, Jukka Kemppainen, Olof Solin, Fredrik Lonnqvist, Ele Ferrannini, Juhani Knuuti, Pirjo Nuutila
Journal: Diabetes Care (2003)

Impaired insulin-mediated hepatic glucose uptake (HGU) has been implicated in the hyperglycemia of type 2 diabetes. We examined the effects of metformin (2 g/day) and rosiglitazone (8 mg/day) monotherapy on HGU and its relation to subcutaneous fat, visceral fat (VF), and whole-body insulin-mediated glucose metabolism in type 2 diabetic patients.Glucose uptake was measured before and after 26 weeks of treatment using positron emission tomography with [(18)F]2-fluoro-2-deoxyglucose during euglycemic hyperinsulinemia; fat depots were quantified by magnetic resonance imaging.Fasting plasma glucose levels were significantly decreased after either rosiglitazone (-0.9 +/- 0.5 mmol/l) or metformin treatment (-1.1 +/- 0.5 mmol/l) in comparison with placebo; only metformin was associated with weight loss (P < 0.02 vs. placebo). When controlling for the latter, the placebo-subtracted change in whole-body glucose uptake averaged -1 +/- 4 micromol x min(-1) x kg(-1) in metformin-treated patients (NS) and +9 +/- 3 micromol x min(-1) x kg(-1) in rosiglitazone-treated patients (P = 0.01). Both rosiglitazone and metformin treatment were associated with an increase in HGU; versus placebo, the change reached statistical significance when controlling for sex (placebo-subtracted values = +0.008 +/- 0.004 micromol x min(-1) x kg(-1) x pmol/l(-1), P < 0.03, for metformin; and +0.007 +/- 0.004, P < 0.07, for rosiglitazone). After treatment with either drug, insulin-mediated VF glucose uptake (VFGU) was higher than with placebo. In the whole dataset, changes in HGU were negatively related to changes in HbA(1c) (r = 0.43, P = 0.01) and positively associated with changes in VFGU (r = 0.48, P < 0.01).We conclude that both metformin and rosiglitazone monotherapy increase HGU in type 2 diabetes; direct drug actions, better glycemic control, and enhanced VF insulin sensitivity are likely determinants of this phenomenon.
Microbiology of bacterial translocation in humans
Authors: C J O’Boyle, J MacFie, C J Mitchell, D Johnstone, P M Sagar, P C Sedman
Journal: Gut (1998)

Gut translocation of bacteria has been shown in both animal and human studies. Evidence from animal studies that links bacteria translocation to the development of postoperative sepsis and multiple organ failure has yet to be confirmed in humans.To examine the spectrum of bacteria involved in translocation in surgical patients undergoing laparotomy and to determine the relation between nodal migration of bacteria and the development of postoperative septic complications.Mesenteric lymph nodes (MLN), serosal scrapings, and peripheral blood from 448 surgical patients undergoing laparotomy were analysed using standard microbiological techniques.Bacterial translocation was identified in 69 patients (15.4%). The most common organism identified was Escherichia coli (54%). Both enteric bacteria, typical of indigenous intestinal flora, and non-enteric bacteria were isolated. Postoperative septic complications developed in 104 patients (23%). Enteric organisms were responsible in 74% of patients. Forty one per cent of patients who had evidence of bacterial translocation developed sepsis compared with 14% in whom no organisms were cultured (p < 0.001). Septic morbidity was more frequent when a greater diversity of bacteria resided within the MLN, but this was not statistically significant.Bacterial translocation is associated with a significant increase in the development of postoperative sepsis in surgical patients. The organisms responsible for septic morbidity are similar in spectrum to those observed in the mesenteric lymph nodes. These data strongly support the gut origin hypothesis of sepsis in humans.
Nanotechnology in Radiation Oncology
Authors: Andrew Z. Wang, Joel E. Tepper
Journal: Journal of Clinical Oncology (2014)

Nanotechnology, the manipulation of matter on atomic and molecular scales, is a relatively new branch of science. It has already made a significant impact on clinical medicine, especially in oncology. Nanomaterial has several characteristics that are ideal for oncology applications, including preferential accumulation in tumors, low distribution in normal tissues, biodistribution, pharmacokinetics, and clearance, that differ from those of small molecules. Because these properties are also well suited for applications in radiation oncology, nanomaterials have been used in many different areas of radiation oncology for imaging and treatment planning, as well as for radiosensitization to improve the therapeutic ratio. In this article, we review the unique properties of nanomaterials that are favorable for oncology applications and examine the various applications of nanotechnology in radiation oncology. We also discuss the future directions of nanotechnology within the context of radiation oncology.