tbuckley/cabot-search huggingface dataset:
Autocrine motility factor enhances hepatoma cell invasion across the basement membrane through activation of β1 integrins
Authors: T Torimura
Journal: Hepatology (2001)

Autocrine motility factor/phosphohexose isomerase (AMF/PHI) is a cytokine that is linked to tumor invasion and metastasis. In hepatocellular carcinoma (HCC) tissues, hepatoma cells produce AMF/PHI and its receptor, Mr 78,000 glycoprotein (gp78), is strongly detected in hepatoma cells invading into the stroma and tumor thrombi in the portal vein. Here, we investigated the mechanism of hepatoma cell invasion through Matrigel induced by AMF/PHI using 3 hepatoma cell lines. Production of AMF/PHI, phosphorylation of MEK1/2, and Rho activity were investigated by immunoblotting. Expression of AMF/PHI and gp78 was observed by confocal fluorescence microscopy. The influence of AMF/PHI on activated integrin β1 subunit expression was evaluated by flow cytometry. Changes in invasion, adhesion, and motility induced by AMF/PHI were evaluated using chemoinvasion, adhesion, and phagokinetic track motility assays. The effect of AMF/PHI on matrix metalloproteinase (MMP) secretion was evaluated by gelatin zymography. Hepatoma cells produced AMF/PHI and expressed gp78. Although AMF/PHI was ubiquitously detected, gp78 was strongly expressed in migrating cells. AMF/PHI induced up-regulation of activated integrin β1 subunit expression. AMF/PHI stimulated hepatoma cell invasion through Matrigel, and stimulated the adhesion, motility, and MMP-2 secretion of hepatoma cells. The latter effects were suppressed by the function-blocking antibody for integrin β1 subunit. AMF/PHI also enhanced Rho activity and the phosphorylation of MEK1 and MEK 2. Our results indicate that AMF/PHI enhances hepatoma cell invasion through Matrigel in an autocrine manner by stimulating the adhesion, motility, and MMP-2 secretion of these cells through activation of β1 integrins.
Direct and Functional Biomarkers of Vitamin B6 Status
Authors: Per Magne Ueland, Arve Ulvik, Luisa Rios-Avila, Øivind Midttun, Jesse F. Gregory
Journal: Annual Review of Nutrition (2015)

Measures of B6 status are categorized as direct biomarkers and as functional biomarkers. Direct biomarkers measure B6 vitamers in plasma/serum, urine and erythrocytes, and among these plasma pyridoxal 5'-phosphate (PLP) is most commonly used. Functional biomarkers include erythrocyte transaminase activities and, more recently, plasma levels of metabolites involved in PLP-dependent reactions, such as the kynurenine pathway, one-carbon metabolism, transsulfuration (cystathionine), and glycine decarboxylation (serine and glycine). Vitamin B6 status is best assessed by using a combination of biomarkers because of the influence of potential confounders, such as inflammation, alkaline phosphatase activity, low serum albumin, renal function, and inorganic phosphate. Ratios between substrate-products pairs have recently been investigated as a strategy to attenuate such influence. These efforts have provided promising new markers such as the PAr index, the 3-hydroxykynurenine:xanthurenic acid ratio, and the oxoglutarate:glutamate ratio. Targeted metabolic profiling or untargeted metabolomics based on mass spectrometry allow the simultaneous quantification of a large number of metabolites, which are currently evaluated as functional biomarkers, using data reduction statistics.
Dietary protein and renal function.
Authors: A J King, A S Levey
Journal: Journal of the American Society of Nephrology (1993)

Protein intake has been recognized as a modulator of renal function for over half a century. This review analyzes the renal response induced by changes in habitual protein intake and with acute amino acid infusion or a meat meal in humans and animals. The pattern and magnitude of changes in GFR and creatinine clearance are examined along with a discussion of the effect of the variability of these measurements among individuals and populations on the interpretation of clinical studies. Potential mechanisms of protein-induced changes in GFR and creatinine clearance are examined, including changes in the hormonal milieu, glomerular hemodynamics, and other intrarenal processes. Habitual dietary protein consumption varies significantly with respect to age, gender, and lean body mass--factors that are well known to influence GFR. This correlation raises the possibility that (1) variation in dietary protein intake may account, at least in part, for the differences in renal function among individuals; and (2) the level of protein intake should be assessed in defining the normal range of renal function.
STUDIES ON SPREADING FACTORS
Authors: Oscar Hechter
Journal: The Journal of Experimental Medicine (1947)

The spreading response induced by intradermal administration of hyaluronidase is influenced not only by enzyme concentration, but also by the volume and pressure of the injection. These pressure-volume factors influence the rate of spreading and determine the final area of spreading. When a constant volume is injected, the rate of spreading to the area determined by the volume of injection is a function of the enzyme concentration. These and other findings have led to the conclusion that hyaluronidase is an effective spreading agent only when the slow diffusion of enzyme in skin is accelerated by a localized increase of interstitial pressure and volume. These considerations of hyaluronidase action in skin have been utilized to explain the shape of the dosage-response curve of hyaluronidase spreading activity, and the differences in the spreading reactions between crude snake venoms and purified hyaluronidase. The significance of the findings as related to the rôle of hyaluronidase in bacterial invasiveness, and in the assay of S. F. are briefly discussed.
Intensity-Modulated Radiation Therapy With or Without Chemotherapy for Nasopharyngeal Carcinoma: Radiation Therapy Oncology Group Phase II Trial 0225
Authors: Nancy Lee, Jonathan Harris, Adam S. Garden, William Straube, Bonnie Glisson, Ping Xia, Walter Bosch, William H. Morrison, Jeanne Quivey, Wade Thorstad, Christopher Jones, K. Kian Ang
Journal: Journal of Clinical Oncology (2009)

To investigate the feasibility of intensity-modulated radiation therapy (IMRT) with or without chemotherapy, and to assess toxicities, failure patterns, and survivals in patients with nasopharyngeal carcinoma (NPC).Radiation consisted of 70 Gy given to the planning target volumes of primary tumor plus any N+ disease and 59.4 Gy given to subclinical disease, delivered over 33 treatment days. Patients with stage T2b or greater or with N+ disease also received concurrent cisplatin (100 mg/m(2)) on days 1, 22, and 43 followed by adjuvant cisplatin (80 mg/m(2)) on day 1; fluorouracil (1,000 mg/m(2)/d) on days 1 through 4 administered every 4 weeks for three cycles. Tumor, clinical status, and acute/late toxicities were assessed. The primary objective was to test the transportability of IMRT to a multi-institutional setting.Between February 2003 and November 2005, 68 patients with stages I through IVB NPC (of which 93.8% were WHO types 2 and 3) were enrolled. Prescribed IMRT (target delineation) was given to 83.8%, whereas 64.9% received chemotherapy per protocol. The estimated 2-year local progression-free (PF), regional PF, locoregional PF, and distant metastasis-free rates were 92.6%, 90.8%, 89.3%, and 84.7%, respectively. The estimated 2-year PF and overall survivals were 72.7% and 80.2%, respectively. Acute grade 4 mucositis occurred in 4.4%, and the worst late grade 3 toxicities were as follows: esophagus, 4.7%; mucous membranes, 3.1%; and xerostomia, 3.1%. The rate of grade 2 xerostomia at 1 year from start of IMRT was 13.5%. Only two patients complained of grade 3 xerostomia, and none had grade 4 xerostomia.It was feasible to transport IMRT with or without chemotherapy in the treatment of NPC to a multi-institutional setting with 90% LRPF rate reproducing excellent reports from single institutions. Minimal grade 3 and lack of grade 4 xerostomia were encouraging.
The genetics and immunobiology of IgA nephropathy
Authors: Krzysztof Kiryluk, Jan Novak
Journal: Journal of Clinical Investigation (2014)

IgA nephropathy (IgAN) represents the leading cause of kidney failure among East Asian populations and the most frequent form of primary glomerulonephritis among Europeans. Patients with IgAN develop characteristic IgA1-containing immune complexes that deposit in the glomerular mesangium, producing progressive kidney injury. Recent studies define IgAN as an autoimmune trait of complex architecture with a strong genetic determination. This Review summarizes new insights into the role of the O-glycosylation pathway, anti-glycan immune response, mucosal immunity, antigen processing and presentation, and the alternative complement pathway in the pathogenesis of IgAN.
Cilostazol inhibits cytokine-induced nuclear factor- B activation via AMP-activated protein kinase activation in vascular endothelial cells
Authors: Y. Hattori, K. Suzuki, A. Tomizawa, N. Hirama, T. Okayasu, S. Hattori, H. Satoh, K. Akimoto, K. Kasai
Journal: Cardiovascular Research (2008)

Cilostazol is a selective inhibitor of phosphodiesterase 3 that increases intracellular cyclic AMP (cAMP) levels and activates protein kinase A, thereby inhibiting platelet aggregation and inducing peripheral vasodilation. We hypothesized that cilostazol may prevent inflammatory cytokine induced-nuclear factor (NF)-κB activation by activating AMP-activated protein kinase (AMPK) in vascular endothelial cells. Cilostazol was observed to activate AMPK and its downstream target, acetyl-CoA carboxylase, in human umbilical vein endothelial cells (HUVEC). Phosphorylation of AMPK with cilostazol was not affected by co-treatment with an adenylate cyclase inhibitor, SQ 22536, and a cell-permeable cAMP analogue, pCTP-cAMP, did not induce AMPK phosphorylation and had no effect on cilostazol-induced AMPK phosphorylation, suggesting that cilostazol-induced AMPK activation occurs through a signalling pathway independent of cyclic AMP. Cilostazol also dose-dependently inhibited tumour necrosis factor alpha (TNFα)-induced NF-κB activation and TNFα-induced IκB kinase activity. Furthermore, cilostazol attenuated the TNFα-induced gene expression of various pro-inflammatory and cell adhesion molecules, such as vascular cell adhesion molecule-1, E-selectin, intercellular adhesion molecule-1, monocyte chemoattractant protein-1 (MCP-1), and PECAM-1 in HUVEC. RNA interference of AMPKα1 or the AMPK inhibitor compound C attenuated cilostazol-induced inhibition of NF-κB activation by TNFα. In the light of these findings, we suggest that cilostazol might attenuate the cytokine-induced expression of adhesion molecule genes by inhibiting NF-κB following AMPK activation.
Utility of18fluoro-deoxyglucose positron emission tomography for prognosis and response assessments in a phase 2 study of romidepsin in patients with relapsed or refractory peripheral T-cell lymphoma
Authors: S. Horwitz, B. Coiffier, F. Foss, H.M. Prince, L. Sokol, M. Greenwood, D. Caballero, F. Morschhauser, L. Pinter-Brown, S.P. Iyer, A. Shustov, J. Nichols, J. Balser, B. Balser, B. Pro
Journal: Annals of Oncology (2015)

For patients with peripheral T-cell lymphoma (PTCL), the value of (18)fluoro-deoxyglucose positron emission tomography (FDG-PET) scans for assessing prognosis and response to treatment remains unclear. The utility of FDG-PET, in addition to conventional radiology, was examined as a planned exploratory end point in the pivotal phase 2 trial of romidepsin for the treatment of relapsed/refractory PTCL.
Systolic blood pressure is superior to other haemodynamic predictors of outcome in community acquired pneumonia
Authors: J D Chalmers, A Singanayagam, A T Hill
Journal: Thorax (2008)

Introduction: Admission blood pressure (BP) assessment is a central component of severity assessment for community acquired pneumonia. The aim of this study was to establish which readily available haemodynamic measure on admission is most useful for predicting severity in patients admitted with community acquired pneumonia. Methods: A prospective observational study of patients admitted with community acquired pneumonia was conducted in Edinburgh, UK. The measurements compared were systolic and diastolic BP, mean arterial pressure and pulse pressure. The outcomes of interest were 30 day mortality and the requirement for mechanical ventilation and/or inotropic support. Results: Admission systolic BP <90 mm Hg, diastolic BP ⩽60 mm Hg, mean arterial pressure <70 mm Hg and pulse pressure ⩽40 mm Hg were all associated with increased 30 day mortality and the need for mechanical ventilation and/or inotropic support on multivariate logistic regression. The AUC values for each predictor of 30 day mortality were as follows: systolic BP <90 mm Hg 0.70; diastolic BP ⩽60 mm Hg 0.59; mean arterial pressure <70 mm Hg 0.64; and pulse pressure ⩽40 mm Hg 0.60. The AUC values for each predictor of need for mechanical ventilation and/or inotropic support were as follows: systolic BP <90 mm Hg 0.70; diastolic BP ⩽60 mm Hg 0.68; mean arterial pressure <70 mm Hg 0.69; and pulse pressure ⩽40 mm Hg 0.59. A simplified CRB65 score containing systolic blood pressure <90 mm Hg alone performed equally well to standard CRB65 score (AUC 0.76 vs 0.74) and to the standard CURB65 score (0.76 vs 0.76) for the prediction of 30 day mortality. The simplified CRB65 score was equivalent for prediction of mechanical ventilation and/or inotropic support to standard CRB65 (0.77 vs 0.77) and to CURB65 (0.77 vs 0.78). Conclusion: Systolic BP is superior to other haemodynamic predictors of 30 day mortality and need for mechanical ventilation and/or inotropic support in community acquired pneumonia. The CURB65 score can be simplified to a modified CRB65 score by omission of the diastolic BP criterion without compromising its accuracy.
Interictal Scalp Electroencephalography and Intraoperative Electrocorticography in Magnetic Resonance Imaging–Negative Temporal Lobe Epilepsy Surgery
Authors: David B. Burkholder, Vlastimil Sulc, E. Matthew Hoffman, Gregory D. Cascino, Jeffrey W. Britton, Elson L. So, W. Richard Marsh, Fredric B. Meyer, Jamie J. Van Gompel, Caterina Giannini, C. Thomas Wass, Robert E. Watson, Gregory A. Worrell
Journal: JAMA Neurology (2014)

<h3>Importance</h3> Scalp electroencephalography (EEG) and intraoperative electrocorticography (ECoG) are routinely used in the evaluation of magnetic resonance imaging–negative temporal lobe epilepsy (TLE) undergoing standard anterior temporal lobectomy with amygdalohippocampectomy (ATL), but the utility of interictal epileptiform discharge (IED) identification and its role in outcome are poorly defined. <h3>Objectives</h3> To determine whether the following are associated with surgical outcomes in patients with magnetic resonance imaging–negative TLE who underwent standard ATL: (1) unilateral-only IEDs on preoperative scalp EEG; (2) complete resection of tissue generating IEDs on ECoG; (3) complete resection of opioid-induced IEDs recorded on ECoG; and (4) location of IEDs recorded on ECoG. <h3>Design, Setting, and Participants</h3> Data were gathered through retrospective medical record review at a tertiary referral center. Adult and pediatric patients with TLE who underwent standard ATL between January 1, 1990, and October 15, 2010, were considered for inclusion. Inclusion criteria were magnetic resonance imaging–negative TLE, standard ECoG performed at the time of surgery, and a minimum follow-up of 12 months. Univariate analysis was performed using log-rank time-to-event analysis. Variables reaching significance with log-rank testing were further analyzed using Cox proportional hazards. <h3>Main Outcomes and Measures</h3> Excellent or nonexcellent outcome at time of last follow-up. An excellent outcome was defined as Engel class I and a nonexcellent outcome as Engel classes II through IV. <h3>Results</h3> Eighty-seven patients met inclusion criteria, with 48 (55%) achieving an excellent outcome following ATL. Unilateral IEDs on scalp EEG (<i>P</i> = .001) and complete resection of brain regions generating IEDs on baseline intraoperative ECoG (<i>P</i> = .02) were associated with excellent outcomes in univariate analysis. Both were associated with excellent outcomes when analyzed with Cox proportional hazards (unilateral-only IEDs, relative risk = 0.31 [95% CI, 0.16-0.64]; complete resection of IEDs on baseline ECoG, relative risk = 0.39 [95% CI, 0.20-0.76]). Overall, 25 of 35 patients (71%) with both unilateral-only IEDs and complete resection of baseline ECoG IEDs had an excellent outcome. <h3>Conclusions and Relevance</h3> Unilateral-only IEDs on preoperative scalp EEG and complete resection of IEDs on baseline ECoG are associated with better outcomes following standard ATL in magnetic resonance imaging–negative TLE. Prospective evaluation is needed to clarify the use of ECoG in tailoring temporal lobectomy.
CXCL12 (SDF-1)/CXCR4 Pathway in Cancer
Authors: Beverly A. Teicher, Simon P. Fricker
Journal: Clinical Cancer Research (2010)

Chemokines, small proinflammatory chemoattractant cytokines that bind to specific G-protein-coupled seven-span transmembrane receptors, are major regulators of cell trafficking and adhesion. The chemokine CXCL12 [stromal cell-derived factor-1 (SDF-1)] binds primarily to CXC receptor 4 (CXCR4; CD184). The binding of CXCL12 to CXCR4 induces intracellular signaling through several divergent pathways initiating signals related to chemotaxis, cell survival and/or proliferation, increase in intracellular calcium, and gene transcription. CXCR4 is expressed on multiple cell types including lymphocytes, hematopoietic stem cells, endothelial and epithelial cells, and cancer cells. The CXCL12/CXCR4 axis is involved in tumor progression, angiogenesis, metastasis, and survival. This pathway is a target for therapeutics that can block the CXCL12/CXCR4 interaction or inhibit downstream intracellular signaling.
TCT-4 Efficacy and Safety of Concurrent Administration of Clopidogrel-loading (600mg) and Prasugrel-loading (60mg) in Patients with Acute ST-Segment Elevation Myocardial Infarction
Authors: Lorenz Raber, Roland Klingenberg, Dik Heg, Henning Kelbaek, Andreas Baumbach, David Tüller, Christian M. Matter, Ran Kornowski, Miodrag C. Ostojic, Francois Mach, Baris Gencer, Aris Moschovitis, Nicolas Rodondi, Giulio G. Stefanini, Clemens von Birgelen, Thomas Zanchin, Marco Roffi, Peter Jüni, Thomas F. Luescher, Stephan Windecker
Journal: Journal of the American College of Cardiology (2013)
Behavioral Symptoms and Psychiatric Diagnoses Among 162 Children in Nonalcoholic or Alcoholic Families
Authors: Marc A. Schuckit, Tom L. Smith, Shelley Radziminski, Ellen K. Heyneman
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: People with alcoholic relatives have high rates of alcohol abuse and dependence as adults, but their patterns of problems earlier in life are less clear. Many studies have not controlled for parental disorders other than alcoholism or for parents' socioeconomic status and general life functioning. The authors' goal was to conduct a study controlling for such factors. METHOD: Personal structured interviews and a behavioral checklist were administered to the parents of 162 children 7 years old or older whose fathers had participated in the 15-year follow-up of 453 sons of alcoholics with no history of antisocial personality disorder and sons of nonalcoholic comparison subjects originally selected from a university population. RESULTS: There was no significant relationship between a family history of alcoholism and childhood diagnoses of conduct, oppositional, or attention deficit disorders or with behavioral checklist summary scores. However, children with alcoholic relatives apparently have a slightly higher risk for drug abuse or dependence than those without alcoholic relatives. CONCLUSIONS: Once familial antisocial disorders and familial socioeconomic status are controlled for, a family history of alcoholism does not appear to relate to childhood externalizing disorders.
Reducing Barriers for Implementation of Bystander-Initiated Cardiopulmonary Resuscitation
Authors: Benjamin S. Abella, Tom P. Aufderheide, Brian Eigel, Robert W. Hickey, W.T. Longstreth, Vinay Nadkarni, Graham Nichol, Michael R. Sayre, Claire E. Sommargren, Mary Fran Hazinski
Journal: Circulation (2008)

S udden cardiac arrest (SCA) is a leading cause of death in the United States and Canada.In the United States, each year Ϸ330 000 people die of coronary heart disease out of the hospital or in emergency departments.Of these, Ͼ150 000 SCAs occur out of the hospital. 1,2Despite the development of electrical defibrillation and the more recent implementation of lay rescuer defibrillation programs, the vast majority of these victims do not leave the hospital alive.In studies over the past 15 years, only 1.4% of patients with out-of-hospital arrest in Los Angeles, Calif, survived to hospital discharge 3 ; in Chicago, Ill, the number was 2%, 4 and in Detroit, Mich, it was Ͻ1%. 5 Conversely, a few municipalities such as Seattle, Wash, report much higher survival rates from SCA-more than 15% in 1 study 6 -which suggests that survival rates need not remain so low.Recent work in Europe and elsewhere has confirmed that a higher survival-to-hospital discharge rate is indeed a realistic goal, with survival rates as high as 9% reported in Amsterdam 7 and 21% in Maribor, Slovenia. 8he American Heart Association (AHA) uses 4 links in the "chain of survival" to illustrate the time-sensitive actions required for victims of SCA: (1) early recognition of the emergency and activation of emergency medical services (EMS), (2) early bystander cardiopulmonary resuscitation (CPR), (3) early delivery of shock(s) from a defibrillator if indicated, and (4) early advanced life support and postresuscitation care.Immediate bystander recognition of the emergency and EMS activation are critical.In many communities, however, these actions may be followed by significant delays,
Mammographic Density and Breast Cancer After Ductal Carcinoma In Situ
Authors: L. A. Habel, J. J. Dignam, S. R. Land, M. Salane, A. M. Capra, T. B. Julian
Journal: JNCI Journal of the National Cancer Institute (2004)

Women with ductal carcinoma in situ (DCIS) are at substantially increased risk for a second breast cancer, but few strong predictors for these subsequent tumors have been identified. We used Cox regression modeling to examine the association between mammographic density at diagnosis of DCIS of 504 women from the National Surgical Adjuvant Breast and Bowel Project B-17 trial and risk of subsequent breast cancer events. In this group of patients, mostly 50 years old or older, approximately 6.6% had breasts categorized as highly dense (i.e., > or =75% of the breast occupied by dense tissue). After adjusting for treatment with radiotherapy, age, and body mass index, women with highly dense breasts had 2.8 (95% confidence interval [CI] = 1.3 to 6.1) times the risk of subsequent breast cancer (DCIS or invasive), 3.2 (95% CI = 1.2 to 8.5) times the risk of invasive breast cancer, and 3.0 (95% CI = 1.2 to 7.5) times the risk of any ipsilateral breast cancer, compared with women with less than 25% of the breast occupied by dense tissue. Our results provide initial evidence that the risk of second breast cancers may be increased among DCIS patients with highly dense breasts.