tbuckley/cabot-search huggingface dataset:
Gene expression profiles in primary pancreatic tumors and metastatic lesions of Ela-c-myc transgenic mice
Authors: Archana Thakur, Aliccia Bollig, Jiusheng Wu, Dezhong J Liao
Journal: Molecular Cancer (2008)

Abstract Background Pancreatic carcinoma usually is a fatal disease with no cure, mainly due to its invasion and metastasis prior to diagnosis. We analyzed the gene expression profiles of paired primary pancreatic tumors and metastatic lesions from Ela- c-myc transgenic mice in order to identify genes that may be involved in the pancreatic cancer progression. Differentially expressed selected genes were verified by semi-quantitative and quantitative RT-PCR. To further evaluate the relevance of some of the selected differentially expressed genes, we investigated their expression pattern in human pancreatic cancer cell lines with high and low metastatic potentials. Results Data indicate that genes involved in posttranscriptional regulation were a major functional category of upregulated genes in both primary pancreatic tumors (PT) and liver metastatic lesions (LM) compared to normal pancreas (NP). In particular, differential expression for splicing factors, RNA binding/pre-mRNA processing factors and spliceosome related genes were observed, indicating that RNA processing and editing related events may play critical roles in pancreatic tumor development and progression. High expression of insulin growth factor binding protein-1 (Igfbp1) and Serine proteinase inhibitor A1 (Serpina1), and low levels or absence of Wt1 gene expression were exclusive to liver metastatic lesion samples. Conclusion We identified Igfbp1, Serpina1 and Wt1 genes that are likely to be clinically useful biomarkers for prognostic or therapeutic purposes in metastatic pancreatic cancer, particularly in pancreatic cancer where c-Myc is overexpressed.
Mice Lacking the Type I Interferon Receptor Are Resistant to <i>Listeria monocytogenes </i>
Authors: Victoria Auerbuch, Dirk G. Brockstedt, Nicole Meyer-Morse, Mary O'Riordan, Daniel A. Portnoy
Journal: The Journal of Experimental Medicine (2004)

Listeria monocytogenes is a facultative intracellular pathogen that induces a cytosolic signaling cascade resulting in expression of interferon (IFN)-β. Although type I IFNs are critical in viral defense, their role in immunity to bacterial pathogens is much less clear. In this study, we addressed the role of type I IFNs by examining the infection of L. monocytogenes in BALB/c mice lacking the type I IFN receptor (IFN-α/βR−/−). During the first 24 h of infection in vivo, IFN-α/βR−/− and wild-type mice were similar in terms of L. monocytogenes survival. In addition, the intracellular fate of L. monocytogenes in macrophages cultured from IFN-α/βR−/− and wild-type mice was indistinguishable. However, by 72 h after inoculation in vivo, IFN-α/βR−/− mice were ∼1,000-fold more resistant to a high dose L. monocytogenes infection. Resistance was correlated with elevated levels of interleukin 12p70 in the blood and increased numbers of CD11b+ macrophages producing tumor necrosis factor α in the spleen of IFN-α/βR−/− mice. The results of this study suggest that L. monocytogenes might be exploiting an innate antiviral response to promote its pathogenesis.
ACCENTUATION OF A "MITRAL MURMUR" BY A TEMPORARY TOXAEMIC CONDITION (ACCOMPANIED BY TEMPORARY NYSTAGMUS)
Authors: G. A. Stephens
Journal: BMJ (1925)

A MITRAL MURMUR BY TOXAEMIA.[TEDICaL OUN 881 up to 440 volts.The room temperature was maintained at 700 to 750 F.Ulcers.-All cases treated have responded after varying periods; one worthy of note was a blacksmith's striker, who did not lose a day's work while undergoing treatment.The following is a typical case: Indolent ulcer of six months' standiing in a girl aged 17.After nine weekly irradiations, beginningii witlh three minutes at a distance of 10 inches and increasing to fifteeii minutes at 6 inches, the ulcer was completely healed.
Pre-transplant Cellular Alloimmunity as Assessed by a Panel of Reactive T-Cells (PRT) and Risk of Post-transplant Allograft Rejection
Authors: M.R. Gupta, M. Vieyra, D.E. Hricik, J.J. Augustine, L. Coleman, R. Starling, E. Poggio, P.S. Heeger
Journal: Journal of Allergy and Clinical Immunology (2007)
Monitoring for Myocardial Ischemia During Noncardiac Surgery
Authors: Mark J. Eisenberg
Journal: JAMA (1992)

<h3>Objective.</h3> —Transesophageal echocardiography (TEE) and 12-lead electrocardiography (ECG) are sophisticated techniques that are increasingly being used to monitor for myocardial ischemia during noncardiac surgery. We examined whether the routine use of these techniques has incremental clinical value in identifying patients at high risk for perioperative ischemic outcomes when compared with preoperative clinical data and intraoperative monitoring using continuous two-lead bipolar ECG. <h3>Design.</h3> —Cohort study. <h3>Setting.</h3> —Veterans Affairs medical center. <h3>Patients.</h3> —A total of 332 men undergoing noncardiac surgery who had or were at high risk for coronary artery disease. <h3>Interventions.</h3> —TEE, 12-lead ECG, and two-lead ECG were performed continuously during noncardiac surgery (47% vascular, 53% nonvascular). Monitoring results were not available to anesthesiologists or surgeons, and data were blindly analyzed after surgery. <h3>Main Outcome Measure.</h3> —Perioperative ischemic outcomes (cardiac death, nonfatal myocardial infarction, unstable angina). <h3>Results.</h3> —In a subset of 285 patients who were adequately studied by all three techniques, 111 patients (39%) were identified as having intraoperative myocardial ischemia (by one or more monitoring techniques). By univariate analysis, intraoperative ischemia was associated with all perioperative cardiac outcomes, including ischemic outcomes, congestive heart failure, and ventricular tachycardia (<i>P</i>≤.02 for each of the three monitoring techniques). However, when monitoring results for TEE and 12-lead ECG were added to a multivariate model that included preoperative clinical data and continuous two-lead ECG results, the incremental value of TEE was small (odds ratio, 2.6; 95% confidence interval [Cl], 1.2 to 5.7;<i>P</i>=.02) and that of 12-lead ECG was not significant (odds ratio, 1.5; 95% Cl, 0.6 to 3.8). Furthermore, when the multivariate analysis was repeated with only ischemic outcomes, neither TEE nor 12-lead ECG retained significant associations (odds ratio, 2.2; 95% Cl, 0.5 to 9.4, and odds ratio, 1.1; 95% Cl, 0.2 to 6.1, respectively). <h3>Conclusion.</h3> —When compared with preoperative clinical data and intraoperative monitoring using two-lead ECG, routine monitoring for myocardial ischemia with TEE or 12-lead ECG during noncardiac surgery has little incremental clinical value in identifying patients at high risk for perioperative ischemic outcomes. (<i>JAMA</i>. 1992;268:210-216)
A Systematic Review of the Prevalence of Schizophrenia
Authors: Sukanta Saha, David Chant, Joy Welham, John McGrath
Journal: PLoS Medicine (2005)

Understanding the prevalence of schizophrenia has important implications for both health service planning and risk factor epidemiology. The aims of this review are to systematically identify and collate studies describing the prevalence of schizophrenia, to summarize the findings of these studies, and to explore selected factors that may influence prevalence estimates.Studies with original data related to the prevalence of schizophrenia (published 1965-2002) were identified via searching electronic databases, reviewing citations, and writing to authors. These studies were divided into "core" studies, "migrant" studies, and studies based on "other special groups." Between- and within-study filters were applied in order to identify discrete prevalence estimates. Cumulative plots of prevalence estimates were made and the distributions described when the underlying estimates were sorted according to prevalence type (point, period, lifetime, and lifetime morbid risk). Based on combined prevalence estimates, the influence of selected key variables was examined (sex, urbanicity, migrant status, country economic index, and study quality). A total of 1,721 prevalence estimates from 188 studies were identified. These estimates were drawn from 46 countries, and were based on an estimated 154,140 potentially overlapping prevalent cases. We identified 132 core studies, 15 migrant studies, and 41 studies based on other special groups. The median values per 1,000 persons (10%-90% quantiles) for the distributions for point, period, lifetime, and lifetime morbid risk were 4.6 (1.9-10.0), 3.3 (1.3-8.2), 4.0 (1.6-12.1), and 7.2 (3.1-27.1), respectively. Based on combined prevalence estimates, we found no significant difference (a) between males and females, or (b) between urban, rural, and mixed sites. The prevalence of schizophrenia in migrants was higher compared to native-born individuals: the migrant-to-native-born ratio median (10%-90% quantile) was 1.8 (0.9-6.4). When sites were grouped by economic status, prevalence estimates from "least developed" countries were significantly lower than those from both "emerging" and "developed" sites (p = 0.04). Studies that scored higher on a quality score had significantly higher prevalence estimates (p = 0.02).There is a wealth of data about the prevalence of schizophrenia. These gradients, and the variability found in prevalence estimate distributions, can provide direction for future hypothesis-driven research.
Benefits of Renin-Angiotensin Blockade on Retinopathy in Type 1 Diabetes Vary With Glycemic Control
Authors: Tasma Harindhanavudhi, Michael Mauer, Ronald Klein, Bernard Zinman, Alan Sinaiko, M. Luiza Caramori
Journal: Diabetes Care (2011)

Optimal glycemic control slows diabetic retinopathy (DR) development and progression and is the standard of care for type 1 diabetes. However, these glycemic goals are difficult to achieve and sustain in clinical practice. The Renin Angiotensin System Study (RASS) showed that renin-angiotensin system (RAS) blockade can slow DR progression. In the current study, we evaluate whether glycemic control influenced the benefit of RAS blockade on DR progression in type 1 diabetic patients.We used RASS data to analyze the relationships between two-steps or more DR progression and baseline glycemic levels in 223 normotensive, normoalbuminuric type 1 diabetic patients randomized to receive 5 years of enalapril or losartan compared with placebo.A total of 147 of 223 patients (65.9%) had DR at baseline (47 of 74 patients [63.5%] in placebo and 100 of 149 patients [67.1%] in the combined treatment groups [P = 0.67]). Patients with two-steps or more DR progression had higher baseline A1C than those without progression (9.4 vs. 8.2%, P < 0.001). There was no beneficial effect of RAS blockade (P = 0.92) in patients with baseline A1C ≤7.5%. In contrast, 30 of 112 (27%) patients on the active treatment arms with A1C >7.5% had two-steps or more DR progression compared with 26 of 56 patients (46%) in the placebo group (P = 0.03).RAS blockade reduces DR progression in normotensive, normoalbuminuric type 1 diabetic patients with A1C >7.5%. Whether this therapy could benefit patients with A1C ≤7.5% will require long-term studies of much larger cohorts.
Pathophysiology of nocturnal scratching in childhood atopic dermatitis: the role of brain-derived neurotrophic factor and substance P
Authors: K-L.E. Hon, M-C.A. Lam, K-Y. Wong, T-F. Leung, P-C. Ng
Journal: British Journal of Dermatology (2007)

Childhood atopic dermatitis (AD) is a distressing disease associated with pruritus and sleep disturbance. The pathophysiology of pruritus is complex and various neuropeptides may be involved.To evaluate whether or not brain-derived neurotrophic factor (BDNF) and substance P are associated with disease severity, quality of life and nocturnal scratching in AD.Patients with AD aged under 18 years were recruited. Disease severity was assessed with the SCORing Atopic Dermatitis (SCORAD) index, and quality of life with the Children's Dermatology Life Quality Index (CDLQI). Concentrations of plasma BDNF, substance P, AD-associated chemokines [cutaneous T-cell attracting cytokine (CTACK), thymus and activation regulated chemokine (TARC)], serum total IgE and eosinophil counts were measured in these patients. All children were instructed to wear the DigiTrac monitor on their dominant wrist while sleeping. The monitor was programmed to record limb motion between 22.00 and 08.00 h the following morning.Twenty-eight children with AD [mean (SD) age 11.1 (3.3) years] were recruited. The mean (SD) SCORAD was 48.1 (21.5) and CDLQI was 8.7 (5.4) in the patients with AD. Their mean (SD) plasma concentrations of BDNF, substance P, CTACK and TARC were 1798 (935), 94 (42), 1424 (719) and 824 (1000) pg mL(-1), respectively. BDNF was significantly correlated with SCORAD (r = 0.478, P = 0.010) and CDLQI (r = 0.522, P = 0.004), whereas substance P showed significant correlation only with CDLQI (r = 0.441, P = 0.019). BDNF and substance P were also significantly correlated with the average (r = 0.905, P < 0.001 and r = 0.925, P < 0.001) and frequency-specific (r = 0.826, P < 0.001 and r = 0.870, P < 0.001) nocturnal wrist activities measured by DigiTrac. However, there was no correlation between BDNF or substance P and the subjective symptoms of pruritus or sleep-loss scores as reported by the parents in the SCORAD. In contrast, serum total IgE levels showed significant correlations with the subjective symptoms of pruritus (r = 0.576, P = 0.001) and sleep loss (r = 0.419, P = 0.027).Serum levels of BDNF and substance P correlate with the clinical score and quality of life score in patients with AD. The strong correlations with nocturnal wrist movements suggest that they may be the pathogenic factors of the annoying symptoms of scratching.
Inhibition of glioma growth by minocycline is mediated through endoplasmic reticulum stress-induced apoptosis and autophagic cell death
Authors: W.-T. Liu, C.-Y. Huang, I.-C. Lu, P.-W. Gean
Journal: Neuro-Oncology (2013)

We have reported that minocycline (Mino) induced autophagic death in glioma cells. In the present study, we characterize the upstream regulators that control autophagy and switch cell death from autophagic to apoptotic. Western blotting and immunofluorescence were used to detect the expressions of eukaryotic translation initiation factor 2α (eIF2α), transcription factor GADD153 (CHOP), and glucose-regulated protein 78 (GRP78). Short hairpin (sh)RNA was used to knock down eIF2α or CHOP expression. Autophagy was assessed by the conversion of light chain (LC)3-I to LC3-II and green fluorescent protein puncta formation. An intracranial mouse model and bioluminescent imaging were used to assess the effect of Mino on tumor growth and survival time of mice. The expression of GRP78 in glioma was high, whereas in normal glia it was low. Mino treatment increased GRP78 expression and reduced binding of GRP78 with protein kinase-like endoplasmic reticulum kinase. Subsequently, Mino increased eIF2α phosphorylation and CHOP expression. Knockdown of eIF2α or CHOP reduced Mino-induced LC3-II conversion and glioma cell death. When autophagy was inhibited, Mino induced cell death in a caspase-dependent manner. Rapamycin in combination with Mino produced synergistic effects on LC3 conversion, reduction of the Akt/mTOR/p70S6K pathway, and glioma cell death. Bioluminescent imaging showed that Mino inhibited the growth of glioma and prolonged survival time and that these effects were blocked by shCHOP. Mino induced autophagy by eliciting endoplasmic reticulum stress response and switched cell death from autophagy to apoptosis when autophagy was blocked. These results coupled with clinical availability and a safe track record make Mino a promising agent for the treatment of malignant gliomas.
Mechanisms of action of lidocaine and quinidine on action potential duration in rabbit cardiac Purkinje fibers. An effect on steady state sodium currents?
Authors: T J Colatsky
Journal: Circulation Research (1982)

The effects of lidocaine and quinidine on rabbit cardiac Purkinje fibers were compared at 37 °C, using action potential and voltage clamp measurements.At therapeutic concentrations (5 /ig/ml), lidocaine shortened the duration of the action potential while quinidine lengthened it.When membrane potential was held constant between -40 and -50 mV by the application of the two-microelectrode voltage clamp, holding current consistently became more outward with lidocaine (+2.3 ± 0.7 nA, mean ± SEM, n = 5), but it either did not change or became more inward with quinidine (-2.1 ± 1.4 nA, n = 5).Both drugs reduced the outward tails generally associated with deactivation of the delayed rectifier current, i x .The depression of delayed rectification by quinidine (-68 ± 6%, n = 5) was greater than that produced by lidocaine (-12 ± 4%, n = 5), and can explain the observed prolongation of the action potential.To evaluate the possibility that lidocaine blocks steady state sodium channels, experiments were performed with tetrodotoxin (TTX), a specific blocker of sodium channels in a variety of excitable membranes.TTX at concentrations of 0.1-5 /tM shortened the action potential, reducing its duration to 50% of control at 1.6 JIM.Voltage clamp experiments revealed a small TTX-sensitive component of steady state current flowing at membrane potentials positive to -80 mV.In the presence of 10 /IM TTX, lidocaine failed to produce additional steady outward membrane current.These data suggest that (1) lidocaine and quinidine differ substantially in their modification of membrane channels, with quinidine having a strong effect on delayed rectification, (2) a TTX-sensitive "window" current exists in the rabbit Purkinje fiber and helps maintain the action potential plateau, and (3) the effect of lidocaine on the cardiac action potential results primarily from block of TTX-sensitive sodium channels, rather than from an enhancement of potassium conductance.
Tumor Necrosis Factor α As a New Target for Renal Cell Carcinoma: Two Sequential Phase II Trials of Infliximab at Standard and High Dose
Authors: Michelle L. Harrison, Eva Obermueller, Nick R. Maisey, Susan Hoare, Kim Edmonds, Ningfeng F. Li, David Chao, Kate Hall, Chooi Lee, Eleni Timotheadou, Kellie Charles, Roger Ahern, D. Mike King, Tim Eisen, Robert Corringham, Mark DeWitte, Frances Balkwill, Martin Gore
Journal: Journal of Clinical Oncology (2007)

Tumor necrosis factor alpha (TNF-alpha) may play a role in renal cell carcinoma (RCC). We performed two sequential phase II studies of infliximab, an anti-TNF-alpha monoclonal antibody, in patients with immunotherapy-resistant or refractory RCC.Patients progressing after cytokine therapy were treated with intravenous infliximab as follows: study 1 (19 patients), 5 mg/kg at weeks 0, 2, and 6, and then every 8 weeks; study 2 (18 patients), 10 mg/kg at weeks 0, 2, and 6, and then every 4 weeks. Treatment continued until disease progression (PD). Response was assessed according to Response Evaluation Criteria in Solid Tumors. Plasma levels of TNF-alpha, CCL2, and interleukin-6 (IL-6) were measured before and during treatment.TNF-alpha and its receptors were detected in malignant cells in RCC biopsies. In study 1, three patients (16%) achieved partial response (PR) and three patients (16%) achieved stable disease (SD). Median duration of response (PR + SD) was 7.7 months (range, 5.0 to 40.5+ months). In study 2, 11 patients (61%) achieved SD. Median duration of response was 6.2 months (range, 3.5 to 24+ months). One patient developed grade 3 hypersensitivity and another died as a result of pulmonary infection/sepsis. Enzyme-linked immunosorbent assay analysis of plasma revealed that higher levels of TNF-alpha at baseline and higher levels of CCL2 during treatment were associated with PD. There were also correlations between higher levels of TNF-alpha, IL-6, and CCL2 and poor survival (< 12 months).This is the first direct clinical evidence suggesting that TNF-alpha may be a therapeutic target in RCC. Plasma levels of TNF-alpha, IL-6, and CCL2 may have predictive and prognostic significance.
Pain Education for Underserved Minority Cancer Patients: A Randomized Controlled Trial
Authors: Karen O. Anderson, Tito R. Mendoza, Richard Payne, Vicente Valero, Guadalupe R. Palos, Arlene Nazario, Stephen P. Richman, Judith Hurley, Ibrahima Gning, Garrett R. Lynch, Dorianne Kalish, Charles S. Cleeland
Journal: Journal of Clinical Oncology (2004)

Previous studies found that African American and Hispanic cancer patients are at risk for undertreatment of pain. We evaluated the efficacy of a pain education intervention for underserved minority patients.Ninety-seven underserved African American and Hispanic outpatients with cancer-related pain were enrolled onto a randomized clinical trial of pain management education. The patients in the education group received a culture-specific video and booklet on pain management. The control group received a video and booklet on nutrition. A research nurse met with each patient to review the materials. We measured changes in pain intensity and pain-related interference 2 to 10 weeks after the intervention, as well as changes in quality of life, perceived pain control, functional status, analgesics, and physician pain assessments.Physicians underestimated baseline pain intensity and provided inadequate analgesics for more than 50% of the sample. Although the ratings for pain intensity and pain interference decreased over time for both groups, there was no statistically significant difference between groups. Pain education did not affect quality of life, perceived pain control, or functional status. African American patients in the education but not the control group reported a significant decrease in pain worst ratings from baseline to first follow-up (P < .01), although this decrease was not maintained at subsequent assessments.Brief education had limited impact on pain outcomes for underserved minority patients, suggesting that more intensive education for patients and interventions for physicians are needed.
Durable Complete Response of Metastatic Gastric Cancer with Anti-Met Therapy Followed by Resistance at Recurrence
Authors: Daniel V. T. Catenacci, Les Henderson, Shu-Yuan Xiao, Premal Patel, Robert L. Yauch, Priti Hegde, Jiping Zha, Ajay Pandita, Amy Peterson, Ravi Salgia
Journal: Cancer Discovery (2011)

A 48 year-old female with chemo-refractory metastatic gastric cancer to the liver was treated on a Phase I clinical trial with MetMAb, a monoclonal antibody targeting the Met tyrosine kinase receptor. The primary tumor had high MET gene polysomy and evidence for an autocrine production of HGF, the growth factor ligand of Met. A complete response was obtained lasting two years; the cancer recurred as a peritoneal deposit invading into the transverse colon and a gastrohepatic ligament node. Compassionate use of MetMAb therapy at recurrence achieved a mixed response--a partial response of the two initial lesions, but with development of multiple new foci of carcinomatosis. Tissue and serum studies evaluating the Met signaling pathway did correlate with MetMAb treatment response initially and at the time of recurrence.This research brief is the first to describe a durable complete response obtained with a molecularly targeted monoclonal antibody, MetMAb, to the receptor tyrosine kinase, Met, in a patient with chemorefractory metastatic gastric cancer. It is also the first to report biomarkers that predicted therapeutic response to Met inhibition.