tbuckley/cabot-search huggingface dataset:
Erwinia infection from environmental sources
Authors: A. von Graevenitz
Journal: JAMA (1971)

To the Editor.—  The recent findings of intravenous fluid contamination with Erwinia organisms has focused attention on these bacteria. At Yale-New Haven Hospital, Erwinia strains were isolated from blood cultures in 1966, 1969, and 1970. The three patients, two males and one female, were 17 (patients 1 and 2) and 28 (patient 3) years old, and had been admitted for reasons other than septicemia, as follows: transverse arrest (patient 1), diabetic ketoacidosis (patient 2), and injuries from a motorcycle accident (patient 3). Within 12 hours after admission, the first two patients experienced chills, tachycardia, and temperatures which rose rapidly to 102 to 103 F. The third patient had two temperature spikes to 105 F on two successive days. All had been given fluids intravenously (without catheter) prior to the temperature spikes, and all were treated promptly with antibiotics, as follows: patient 1 with streptomycin and penicillin, patient 2 with cephalothin,
Hereditary Hormone Excess: Genes, Molecular Pathways, and Syndromes
Authors: Stephen J. Marx, William F. Simonds
Journal: Endocrine Reviews (2005)

Hereditary origin of a tumor helps toward early discovery of its mutated gene; for example, it supports the compilation of a DNA panel from index cases to identify that gene by finding mutations in it. The gene for a hereditary tumor may contribute also to common tumors. For some syndromes, such as hereditary paraganglioma, several genes can cause a similar syndrome. For other syndromes, such as multiple endocrine neoplasia 2, one gene supports variants of a syndrome. Onset usually begins earlier and in more locations with hereditary than sporadic tumors. Mono- or oligoclonal (“clonal”) tumor usually implies a postnatal delay, albeit less delay than for sporadic tumor, to onset and potential for cancer. Hormone excess from a polyclonal tissue shows onset at birth and no benefit from subtotal ablation of the secreting organ. Genes can cause neoplasms through stepwise loss of function, gain of function, or combinations of these. Polyclonal hormonal excess reflects abnormal gene dosage or effect, such as activation or haploinsufficiency. Polyclonal hyperplasia can cause the main endpoint of clinical expression in some syndromes or can be a precursor to clonal progression in others. Gene discovery is usually the first step toward clarifying the molecule and pathway mutated in a syndrome. Most mutated pathways in hormone excess states are only partly understood. The bases for tissue specificity of hormone excess syndromes are usually uncertain. In a few syndromes, tissue selectivity arises from mutation in the open reading frame of a regulatory gene (CASR, TSHR) with selective expression driven by its promoter. Polyclonal excess of a hormone is usually from a defect in the sensor system for an extracellular ligand (e.g., calcium, glucose, TSH). The final connections of any of these polyclonal or clonal pathways to hormone secretion have not been identified. In many cases, monoclonal proliferation causes hormone excess, probably as a secondary consequence of accumulation of cells with coincidental hormone-secretory ability.
Antidepressant Medication Augmented With Cognitive-Behavioral Therapy for Generalized Anxiety Disorder in Older Adults
Authors: Julie Loebach Wetherell, Andrew J. Petkus, Kamila S. White, Hoang Nguyen, Sander Kornblith, Carmen Andreescu, Sidney Zisook, Eric J. Lenze
Journal: American Journal of Psychiatry (2013)

Cognitive-behavioral therapy (CBT) enhanced antidepressant treatment in older adults by reducing worrying in the short term and sustaining remission without long-term pharmacotherapy. Adding CBT may be a useful treatment option for some patients as standard first-line treatment.
Duration of resuscitation efforts and survival after in-hospital cardiac arrest: an observational study
Authors: Zachary D Goldberger, Paul S Chan, Robert A Berg, Steven L Kronick, Colin R Cooke, Mingrui Lu, Mousumi Banerjee, Rodney A Hayward, Harlan M Krumholz, Brahmajee K Nallamothu
Journal: The Lancet (2012)
<i>ZIC1</i> Overexpression Is Oncogenic in Liposarcoma
Authors: Elliott Brill, Ryan Gobble, Christina Angeles, Mariana Lagos-Quintana, Aimee Crago, Bernadette Laxa, Penelope DeCarolis, Lei Zhang, Cristina Antonescu, Nicholas D. Socci, Barry S. Taylor, Chris Sander, Andrew Koff, Samuel Singer
Journal: Cancer Research (2010)

Abstract Liposarcomas are aggressive mesenchymal cancers with poor outcomes that exhibit remarkable histologic diversity (there are five recognized subtypes). Currently, the mainstay of therapy for liposarcoma is surgical excision because liposarcomas are often resistant to traditional chemotherapy. In light of the high mortality associated with liposarcoma and the lack of effective systemic therapy, we sought novel genomic alterations driving liposarcomagenesis that might serve as therapeutic targets. ZIC1, a critical transcription factor for neuronal development, is overexpressed in all five subtypes of liposarcoma compared with normal fat, and in liposarcoma cell lines compared with adipose-derived stem cells. Here, we show that ZIC1 contributes to the pathogenesis of liposarcoma. ZIC1 knockdown inhibits proliferation, reduces invasion, and induces apoptosis in dedifferentiated and myxoid/round cell liposarcoma cell lines, but not in either adipose-derived stem cells or in a lung cancer cell line with low ZIC1 expression. ZIC1 knockdown is associated with increased nuclear expression of p27 proteins and the downregulation of prosurvival target genes BCL2L13, JunD, Fam57A, and EIF3M. Our results show that ZIC1 expression is essential for liposarcomagenesis and that targeting ZIC1 or its downstream targets might lead to novel therapy for liposarcoma. Cancer Res; 70(17); 6891–901. ©2010 AACR.
Loss of Parafibromin Immunoreactivity Is a Distinguishing Feature of Parathyroid Carcinoma
Authors: Min-Han Tan, Carl Morrison, Pengfei Wang, Ximing Yang, Carola J. Haven, Chun Zhang, Ping Zhao, Maria S. Tretiakova, Eeva Korpi-Hyovalti, John R. Burgess, Khee Chee Soo, Wei-Keat Cheah, Brian Cao, James Resau, Hans Morreau, Bin Tean Teh
Journal: Clinical Cancer Research (2004)

Abstract Purpose: A reliable method for diagnosing parathyroid carcinoma has remained elusive over the years, resulting in its under-recognition and suboptimal therapy. Obtaining an accurate diagnosis has become an even more pressing matter with recent evidence that germline HRPT2 gene mutations are found in patients with apparently sporadic parathyroid carcinoma. There is a high prevalence of HRPT2 gene mutations and biallelic inactivation in parathyroid carcinoma. We hypothesize that loss of parafibromin, the protein product of the HRPT2 gene, would distinguish carcinoma from benign tissue. Experimental Design: We generated a novel antiparafibromin monoclonal antibody and performed immunostaining on 52 definite carcinoma specimens, 6 equivocal carcinoma specimens, 88 benign specimens, and 9 hyperparathyroidism-jaw tumor (HPT-JT) syndrome-related adenomas from patients with primary hyperparathyroidism from nine worldwide centers and one national database. Results: We report that the loss of parafibromin nuclear immunoreactivity has 96% sensitivity [95% confidence interval (CI), 85–99%] and 99% specificity (95% CI, 92–100%) in diagnosing definite carcinoma. Inter-observer agreement for evaluation of parafibromin loss was excellent, with unweighted kappa of 0.89 (95% CI, 0.79–0.98). Two equivocal carcinomas misclassified as adenomas were highlighted by parafibromin immunostaining. One of these tumors has since recurred, satisfying criteria for a definite carcinoma. Similarly, eight of nine HPT-JT syndrome-related adenomas showed absent nuclear immunoreactivity. Conclusions: Parafibromin is a promising molecular marker for diagnosing parathyroid carcinoma. The similar loss of parafibromin immunoreactivity in HPT-JT syndrome-related adenomas suggests that this is a pivotal step in parathyroid tumorigenesis.
Selective Mutagenic Activation by Cytochrome P3-450 of Carcinogenic Arylamines Found in Foods
Authors: E. G. Snyderwine, N. Battula
Journal: JNCI Journal of the National Cancer Institute (1989)

Heterocyclic arylamines found in cooked foods including fish and beef are potent mutagens and carcinogens. The purpose of this investigation was to determine the specificity of cytochromes P1-450 and P3-450 toward the metabolic activation of these arylamines. We used a novel mutagenicity test system which combined human cells expressing either recombinant cytochrome P1-450 or P3-450 with Salmonella typhimurium to score mutants. Cytochrome P3-450, a single isoform of the cytochrome P-450 supergene family, bioactivated these food mutagens. Cytochrome P1-450 showed little or no activation of these arylamines but was the isoform predominantly responsible for the activation of the aromatic hydrocarbon benzo[a]pyrene-7,8-diol. This assay system should serve to define the specificities of individual cytochromes P-450 in the metabolic activation of carcinogens.
Interrater Reliability in Clinical Trials of Depressive Disorders
Authors: Benoit H. Mulsant, Kari B. Kastango, Jules Rosen, Roslyn A. Stone, Sati Mazumdar, Bruce G. Pollock
Journal: American Journal of Psychiatry (2002)

The goal of this study was to review the reported methods of rater training, assessment of interrater reliability, and rater drift in clinical trials of treatments for depressive disorders.Two psychiatrists independently identified all original reports of clinical trials relevant to depressive disorders published between 1996 and 2000 in the American Journal of Psychiatry and the Archives of General Psychiatry. Reported methods of rater training, assessment of interrater reliability, and rater drift were systematically summarized.Sixty-three original papers met criteria for inclusion. Only 11 (17%) of the studies reported the number of raters. Only two (9%) of the 22 multicenter and four (10%) of the 41 single-center trials documented rater training. Only nine (22%) of the single-center trials and three (14%) of the multicenter trials reported interrater reliability, despite a median number of five raters (range=2-20). Only three (5%) of the 63 articles reported rater drift.Few published reports of clinical trials of treatments for depressive disorders document adequately the number of raters, rater training, assessment of interrater reliability, and rater drift.
Antibodies in allergy and inflammation. Research tools aiW indicators of disease.
Authors: Lars Yman
Journal: Allergy (1985)

The identification of IgE and the development of the radioallergosorbent test was the initiation of a revolution in the allergy research field. Measurement of allergen specific IgE antibodies is today an integral part of the clinical investigation of patients with suspected allergic disease. However, in addition to a being a routine test for the clinical laboratory, Phadebas RAST has served as the model for a number of modified procedures and as the basis for a wide range of applications. The aim of this presentation is to review and communicate the experience for the benefit of researchers and clinicians working in the field of allergy.
Prostaglandin synthetase activity in acute ulcerative colitis: effects of treatment with sulphasalazine, codeine phosphate and prednisolone.
Authors: P R Smith, D J Dawson, C H Swan
Journal: Gut (1979)

Prostaglandin synthetase activity in rectal biopsy specimens from patients with ulcerative colitis has been shown to fall on treatment with sulphasalazine, local steroids, and codeine phosphate. In vitro studies have shown that sulphasalazine is an inhibitor of prostaglandin synthetase, although less potent than indomethacin, whereas prednisolone and codeine phosphate were inactive. It is suggested that the therapeutic action of sulphasalazine may be related in part to its action in inhibiting prostaglandin biosynthesis.
Intracellular potentiation between two second messenger systems may contribute to cholera toxin induced intestinal secretion in humans
Authors: M R Banks
Journal: Gut (2003)

<b>Background:</b> Cholera toxin (CT) acts on intestinal epithelial cells both directly and indirectly via activation of a secretory neural reflex. The reflex may release acetylcholine as one of its final neurotransmitters. This opens up the possibility of a third mechanism of action for CT, namely a synergistic interaction between two secretagogues acting on different second messenger systems within the epithelial cell. <b>Aims:</b> To establish evidence for cholinergic innervation to human ileal epithelial cells and to investigate whether CT potentiates the action of acetylcholine on human intestinal epithelial cells. <b>Methods:</b> Transverse sections of human ileum were examined for mucosal cholinergic nerves and M3 muscarinic receptors using antibodies raised to choline acetyltransferase and M3 receptors. Short circuit current (Isc) responses and ion flux movements were elicited from T<sub>84</sub> epithelial cell monolayers set up in Ussing chambers. <b>Results:</b> Immunohistochemistry of native human ileal mucosa revealed the presence of both cholinergic nerves and muscarinic M3 receptors located to the basolateral domain of epithelial cells. Secretory responses of T<sub>84</sub> cell monolayers to acetylcholine were greatly potentiated in the presence of CT. This effect, substituting forskolin for CT, was mirrored by increases in basolateral <sup>86</sup>Rb and apical <sup>125</sup>I efflux. Charybdotoxin plus apamin reduced both Isc and <sup>86</sup>Rb efflux evoked by acetylcholine, in the presence of forskolin. <b>Conclusions:</b> Human ileal mucosa receives a direct cholinergic innervation to its epithelial cells. Secretory effects of acetylcholine on epithelial cells are augmented in the presence of CT. Such a synergistic response is dependent on optimum opening of basolateral potassium channels by acetylcholine and apical chloride channels by CT. The interaction may contribute to the mechanism of action of cholera toxin induced secretory diarrhoea.
Psychiatric Screening with Automated Multiphasic Health Testing in the VA Admission Procedure
Authors: RICHARD E. GORDON, LESLIE BIELEN, ANNE WATTS
Journal: American Journal of Psychiatry (1973)

A total of 241 veterans who applied for admission to a Veterans Administration hospital underwent automated multiphasic health testing and services (AMHTS). The authors compare test findings with the admitting physician's decision as to whether or not a patient should be worked up by the psychiatry service for admission. The findings indicate that an AMHTS system may be able to assist the admitting physician in making this decision: Discriminant function analysis from the patient's history questionnaire simulated the physician's decision fairly well.
Psychosocial Interventions To Improve Successful Aging
Authors: S Leonard Syme
Journal: Annals of Internal Medicine (2003)

Interventions designed to encourage people to change high-risk behavior have not been very successful. This is an important challenge because the number of older people in the population will double within the next 20 to 30 years. The increase will put enormous strain on an already overburdened medical care system. We therefore will need to put more emphasis on disease prevention programs. Helping people change high-risk behavior will be the key to prevention. To develop more effective prevention programs, we will have to train a new generation of experts who can not only provide people with risk information but also work with them as partners in achieving mutually agreed upon goals.
Effect of granulocyte colony-stimulating factor administration in elderly patients with aggressive non-Hodgkin's lymphoma treated with a pirarubicin-combination chemotherapy regimen
Authors: A. Guerci, P. Lederlin, F. Reyes, D. Bordessoule, C. Sebban, H. Tilly, Y. Kerneis, P. Biron, C. Gisselbrecht, R. Herbrecht, B. Coiffier
Journal: Annals of Oncology (1996)
Type I and III collagen content and fibre distribution in normal human skin during ageing
Authors: C.R. LOVELL, K.A. SMOLENSKI, V.C. DUANCE, N.D. LIGHT, S. YOUNG, M. DYSON
Journal: British Journal of Dermatology (1987)

The content of type I and III collagen in normal human skin from subjects of different ages was studied by means of a new high performance liquid chromatography method and by SDS-polyacrylamide gel electrophoresis and scanning electron microscopy. The ratio of types I and III collagen in covered skin remained constant throughout childhood and young adult life and the proportion of type III was shown to be the same as previously reported. However, in the elderly, the proportion of type III collagen in the dermis increased to a variable degree. Scanning electron microscopic examination showed a decrease in the number of collagen fibre bundles with age. Average bundle width varied significantly with age. These results may reflect an impaired synthesis of type I collagen in aged skin.
Oxidized Phospholipids Reduce Vascular Leak and Inflammation in Rat Model of Acute Lung Injury
Authors: Stephanie Nonas, Ian Miller, Kamon Kawkitinarong, Santipongse Chatchavalvanich, Irina Gorshkova, Valery N. Bochkov, Norbert Leitinger, Viswanathan Natarajan, Joe G. N. Garcia, Konstantin G. Birukov
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Acute inflammation and vascular leak are cardinal features of acute lung injury and the acute respiratory distress syndrome. Nonspecific tissue inflammation and injury in response to infectious and noninfectious insults lead to oxidative stress and the generation of lipid oxidation products, which may inhibit the acute inflammatory response to bacterial components.To test the hypothesis that oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OxPAPC) may attenuate the acute lung inflammatory response to lipopolysaccharide (LPS) and enhance lung vascular barrier recovery, we used in vivo and in vitro models of LPS-induced lung injury.Rats received intratracheal aerosolized LPS (5 mg/kg) or sterile water with concurrent intravenous injection of OxPAPC (0.5-6.0 mg/kg) or saline alone. Nonoxidized PAPC was used as a control. At 18 h, bronchoalveolar lavage was performed and the lungs were removed for histologic analysis. Measurements of endothelial transmonolayer electrical resistance and immunofluorescent analysis of monolayer integrity were used in an in vitro model of LPS-induced lung vascular barrier dysfunction.In vivo, aerosolized intratracheal LPS induced lung injury with profound increases in bronchoalveolar lavage neutrophils, protein content, and the inflammatory cytokines interleukin 6 and interleukin 1beta, as well as tissue neutrophils. OxPAPC, but not nonoxidized PAPC, markedly attenuated the LPS-induced tissue inflammation, barrier disruption, and cytokine production over a range of doses. In vitro, oxidized phospholipids attenuated LPS-induced endothelial barrier disruption and reversed LPS-induced cytoskeletal remodeling and disruption of monolayer integrity.These studies demonstrate in vivo and in vitro protective effects of oxidized phospholipids on LPS-induced lung dysfunction.
Noncardiothoracic nonobstetric surgery in mild-to-moderate pulmonary hypertension
Authors: L. C. Price, D. Montani, X. Jais, J. R. Dick, G. Simonneau, O. Sitbon, F. J. Mercier, M. Humbert
Journal: European Respiratory Journal (2009)

The anaesthetic management and follow-up of well-characterised patients with pulmonary arterial hypertension presenting for noncardiothoracic nonobstetric surgery has rarely been described. The details of consecutive patients and perioperative complications during the period January 2000 to December 2007 were reviewed. Repeat procedures in duplicate patients were excluded. Longer term outcomes included New York Heart Association (NYHA) functional class, 6-min walking distance and invasive haemodynamics. A total of 28 patients were identified as having undergone major (57%) or minor surgery under general (50%) and regional anaesthesia. At the time of surgery, 75% of patients were in NYHA functional class I-II. Perioperative deaths occurred in 7%. Perioperative complications, all related to pulmonary hypertension, occurred in 29% of all patients and in 17% of those with no deaths during scheduled procedures. Most (n = 11, 92%) of the complications occurred in the first 48 h following surgery. In emergencies (n = 4), perioperative complication and death rates were higher (100 and 50%, respectively; p<0.005). Risk factors for complications were greater for emergency surgery (p<0.001), major surgery (p = 0.008) and a long operative time (193 versus 112 min; p = 0.003). No significant clinical or haemodynamic deterioration was seen in survivors at 3-6 or 12 months of post-operative follow-up. Despite optimal management in this mostly nonsevere pulmonary hypertension population, perioperative complications were common, although survivors remained stable. Emergency procedures, major surgery and long operations were associated with increased risk.
The Insulin-Like Growth Factor-I Receptor Kinase Inhibitor, NVP-ADW742, Sensitizes Small Cell Lung Cancer Cell Lines to the Effects of Chemotherapy
Authors: G. Sakuntala Warshamana-Greene, Julie Litz, Elisabeth Buchdunger, Carlos García-Echeverría, Francesco Hofmann, Geoffrey W. Krystal
Journal: Clinical Cancer Research (2005)

Insulin-like growth factor-I (IGF-I) is a potent growth factor for small cell lung cancer (SCLC) in both the autocrine and endocrine context. It also inhibits chemotherapy-induced apoptosis through activation of the phosphatidylinositol 3-kinase (PI3K)-Akt pathway and we have previously shown that inhibition of this signaling pathway enhances sensitivity of SCLC cell lines to chemotherapy. The purpose of this study was to determine whether the novel IGF-I receptor (IGF-IR) kinase inhibitor, NVP-ADW742, sensitizes SCLC cell lines to etoposide and carboplatin, which are commonly used in the treatment of SCLC.Cell growth in the presence of various combinations of NVP-ADW742, imatinib (STI571; Gleevec/Glivec), and chemotherapeutic agents was monitored using a 3-(4,5 dimethylthiazol-2yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay and analyzed using the Chou-Talalay multiple-drug-effect equation. Induction of apoptosis was assessed using terminal deoxynucleotide transferase-mediated dUTP nick end labeling (TUNEL) and Western blot analysis of procaspase 3 and poly(ADP-ribose)polymerase cleavage. IGF-I-induced vascular endothelial cell growth factor expression was monitored by Northern blot and ELISA.NVP-ADW742 synergistically enhanced sensitivity of multiple SCLC cell lines to etoposide and carboplatin. Maximal enhancement occurred at concentrations of NVP-ADW742 that eliminated basal PI3K-Akt activity in individual cell lines. In the WBA cell line, in which the c-Kit receptor tyrosine kinase is partly responsible for basal PI3K-Akt activity, the combination of NVP-ADW742 and imatinib was superior to NVP-ADW742 alone in sensitizing the cells to etoposide. Enhancement of the sensitivity of SCLC cell lines to etoposide, as determined by MTT assay, correlated closely with sensitization to the induction of apoptosis as measured by TUNEL and caspase activation assays. Treatment with NVP-ADW742 also eliminated IGF-I-mediated expression of vascular endothelial cell growth factor, suggesting that in addition to enhancing sensitivity of SCLC to chemotherapy, this kinase inhibitor could potentially inhibit angiogenesis in vivo.Inhibition of IGF-IR signaling synergistically enhances the sensitivity of SCLC to etoposide and carboplatin. This enhancement in sensitivity to chemotherapy tightly correlates with inhibition of PI3K-Akt activation. Future SCLC clinical trials incorporating IGF-IR inhibitors alone or in combination with other kinase inhibitors should include assessment of PI3K-Akt activity as a pharmacodynamic end-point.