tbuckley/cabot-search huggingface dataset:
A <i>Survivin</i> Gene Signature Predicts Aggressive Tumor Behavior
Authors: Whitney Salz, Dan Eisenberg, Janet Plescia, David S. Garlick, Robert M. Weiss, Xue-Ru Wu, Tung-Tien Sun, Dario C. Altieri
Journal: Cancer Research (2005)

Gene signatures that predict aggressive tumor behavior at the earliest stages of disease, ideally before overt tissue abnormalities, are urgently needed. To search for such genes, we generated a transgenic model of survivin, an essential regulator of cell division and apoptosis overexpressed in cancer. Transgenic expression of survivin in the urinary bladder did not cause histologic abnormalities of the urothelium. However, microarray analysis revealed that survivin-expressing bladders exhibited profound changes in gene expression profile affecting extracellular matrix and inflammatory genes. Following exposure to a bladder carcinogen, N-butyl-N-(4-hydroxybutyl) nitrosamine (OH-BBN), survivin transgenic animals exhibited accelerated tumor progression, preferential incidence of tumors as compared with premalignant lesions, and dramatically abbreviated survival. Conversely, transgenic expression of a survivin Thr34-->Ala dominant-negative mutant did not cause changes in gene expression or accelerated tumor progression after OH-BBN treatment. Therefore, survivin expression induces global transcriptional changes in the tissue microenvironment that may promote tumorigenesis. Detection of survivin or its associated gene signature may provide an early biomarker of aggressive tumor behavior before the appearance of tissue abnormalities.
Percutaneous cervical cordotomy for the control of pain in patients with pleural mesothelioma
Authors: M B Jackson, D Pounder, C Price, A W Matthews, E Neville
Journal: Thorax (1999)

Severe chest pain is common in mesothelioma. Percutaneous cervical cordotomy, which interrupts the spinothalamic tract at the C1/C2 level causing contralateral loss of pain sensation, is particularly appropriate in mesothelioma as the tumour is unilateral and systemic analgesia may be ineffective and is limited by harmful side effects.A retrospective review was performed to determine the effectiveness and complication rate of this procedure.Fifty two patients were using opioids prior to cordotomy. The median daily dose of morphine before and after cordotomy was 100 mg (range 0-1000 mg) and 20 mg (range 0-520 mg), respectively (p < 0.001). Forty three patients (83%) had a reduction in pain such that their dose of opioid could be at least halved. Twenty patients (38%) were able to stop completely. Recurrence of pain requiring an increase in opioid medication was recorded in 18 patients at a median time of nine weeks (range 0.7-26 weeks). Four patients developed mild weakness, two had troublesome dysaesthesia. The median time from cordotomy to death was 13 weeks (range 0.3-52 weeks). Six early deaths within two weeks of cordotomy occurred early in the series and reflect postoperative chest infection and poor selection as the patients were in the terminal stages of mesothelioma.Percutaneous cervical cordotomy is successful in treating pain from mesothelioma. There was a low complication rate in this series. Referral to a unit experienced in cordotomy is recommended as soon as pain from chest wall invasion is suspected.
Recombinant basic fibroblast growth factor stimulates wound healing in healing-impaired db/db mice.
Authors: R Tsuboi, D B Rifkin
Journal: The Journal of Experimental Medicine (1990)

The stimulatory effect of recombinant basic fibroblast growth factor (bFGF) on wound healing was assessed using healing-impaired (db/db) mice. Full-thickness wounds were made in female diabetic C57BL/KsJ db/db mice, and their normal (db/+) littermates with a punch biopsy instrument. Recombinant bFGF was applied locally to the open wound once a day. The mice were later killed and histological sections of the wounds were prepared. The degree of wound healing was evaluated using several histological parameters such as degree of reepithelialization, granulation tissue thickness, matrix density, number of infiltrated cells, and number of capillaries. Wounds from normal mice displayed good reepithelialization rates and granulation tissue formation, while wounds from db/db mice had poor responses, especially in the dermal parameters. Although the application of bFGF to wounds in the normal (db/+) mice had little effect, application of bFGF to wounds in db/db mice induced significant responses in all of the dermal parameters compared with nontreated db/db mice (p less than 0.001). In the presence of bFGF, these parameters approximated those observed in nontreated littermates. A minimum of 0.5 microgram bFGF in either single or multiple applications was required for a significant effect. bFGF that was either boiled or pretreated with neutralizing antibody had little stimulatory effect. Time-course experiments indicated that the granulation response in bFGF-treated mice peaked between 8 and 12 d, and decreased after 12 d, while matrix density continued to increase until the 18th day (p less than 0.05). The breaking strength of healed linear wounds in db/db mice was also decreased when compared with heterozygous littermates. This parameter was also improved by the administration of bFGF to the wounds (p less than 0.05).
Endothelial-Leukocyte Adhesion Molecules
Authors: M P Bevilacqua
Journal: Annual Review of Immunology (1993)

Endothelial-Leukocyte Adhesion Molecules, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/immunol/11/1/annurev.iy.11.040193.004003-1.gif
Identification of Cripto-1 as a Novel Serologic Marker for Breast and Colon Cancer
Authors: Caterina Bianco, Luigi Strizzi, Mario Mancino, Aasia Rehman, Shin Hamada, Kazuhide Watanabe, Antonella De Luca, Brenda Jones, Gabriela Balogh, Jose Russo, Daniel Mailo, Raffaele Palaia, Giuseppe D'Aiuto, Gerardo Botti, Francesco Perrone, David S. Salomon, Nicola Normanno
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Human Cripto-1 (CR-1), a cell membrane glycosylphosphatidylinositol-anchored glycoprotein that can also be cleaved from the membrane, is expressed at high levels in several different types of human tumors. We evaluated whether CR-1 is present in the plasma of patients with breast and colon cancer, and if it can represent a new biomarker for these malignancies. Experimental Design: We determined CR-1 plasma levels using a sandwich-type ELISA in 21 healthy volunteers, 54 patients with breast cancer, 33 patients with colon carcinoma, and 21 patients with benign breast lesions. Immunohistochemical analysis was also used to assess CR-1 expression in cancerous tissues. Results: Very low levels of CR-1 (mean ± SD) were detected in the plasma of healthy volunteers (0.32 ± 0.19 ng/mL). A statistically significant increase in the levels of plasma CR-1 was found in patients with colon carcinoma (4.68 ± 3.5 ng/mL) and in patients with breast carcinoma (2.97 ± 1.48 ng/mL; P &amp;lt; 0.001). Although moderate levels of plasma CR-1 were found in women with benign lesions of the breast (1.7 ± 0.99 ng/mL), these levels were significantly lower than in patients with breast cancer (P &amp;lt; 0.001). Finally, immunohistochemical analysis and real-time reverse transcription-PCR confirmed strong positivity for CR-1 in colon and/or breast tumor tissues. Conclusion: This study suggests that plasma CR-1 might represent a novel biomarker for the detection of breast and colon carcinomas.
Biophysical Injury Mechanisms in Electrical Shock Trauma
Authors: Raphael C. Lee, Dajun Zhang, Jurgen Hannig
Journal: Annual Review of Biomedical Engineering (2000)

▪ Abstract Electrical shock trauma tends to produce a very complex pattern of injury, mainly because of the multiple modes of frequency-dependent tissue-field interactions. Historically, Joule heating was thought to be the only cause of electrical injuries to tissue by commercial-frequency electrical shocks. In the last 15 years, biomedical engineering research has improved the understanding of the underlying biophysical injury mechanisms. Besides thermal burns secondary to Joule heating, permeabilization of cell membranes and direct electroconformational denaturation of macromolecules such as proteins have also been identified as tissue-damage mechanisms. This review summarizes the physics of tissue injury caused by contact with commercial-frequency power lines, as well as exposure to lightning and radio frequency (RF), microwave, and ionizing radiation. In addition, we describe the anatomic patterns of the resultant tissue injury from these modes of electromagnetic exposures.
Single Low-Dose Administration of Human Recombinant Hepatocyte Growth Factor Attenuates Intimal Hyperplasia in a Balloon-Injured Rabbit Iliac Artery Model
Authors: Satoshi Yasuda, Teruo Noguchi, Masahiro Gohda, Takashi Arai, Nobumasa Tsutsui, Takehisa Matsuda, Hiroshi Nonogi
Journal: Circulation (2000)

Background —Previous studies have shown that repeated systemic administration of human recombinant hepatocyte growth factor (hrHGF) in mg/kg levels modulates the wound-healing process in various diseases. Recently, HGF has been characterized as one of the most potent endothelial-cell–specific growth factors. We tested our hypothesis that local delivery of hrHGF, even at low μg/kg levels (≥2 orders of magnitude lower than systemically administered doses), might attenuate neointimal hyperplasia in response to vascular injury via accelerated reendothelialization. Methods and Results —The iliac artery was denuded in 16 New Zealand White rabbits (3 kg), followed by administration, via a drug delivery catheter, of either hrHGF (10 μg; n=11) or control vehicle (n=5) over 20 minutes. In pilot studies using this device, the drug permeated into the medial tissues, where it persisted for ≥24 hours. Four weeks after the local delivery of hrHGF, computer-assisted morphometric analysis revealed significant reduction in the intimal area (hrHGF, 0.37±0.21 versus control, 0.68±0.16 mm 2 , mean±SD; P &lt;0.05) but no change in the medial area (hrHGF, 1.03±0.21 versus control, 1.10±0.52 mm 2 ). Scanning electron microscopy revealed extensive endothelialization with regular and confluent endothelial cell layer regeneration in the hrHGF-treated vessels. Conclusions —Accelerated endothelialization after local delivery of hrHGF, a novel and potent endothelial cell mitogen, effectively attenuates neointimal proliferation even after single low-dose administration. This observation could have potential therapeutic implications in the prevention of restenosis after angioplasty.
Newly Diagnosed Acute Promyelocytic Leukemia: Arsenic Moves Front and Center
Authors: Elihu H. Estey
Journal: Journal of Clinical Oncology (2011)

Treatment of acute promyelocytic leukemia (APL) with alltrans retinoic acid (ATRA), anthracyclines, and increasingly, cytarabine (ara-C) is often prohibitively expensive in the developing world. This encouraged Ghavamzadeh et al 1 in Iran to treat newly diagnosed APL without these standard drugs and rather to rely on arsenic trioxide (ATO), a drug with well-known activity in relapsed APL. 2 As reported in the article that accompanies this editorial, Ghavamzadeh et al observed a complete remission (CR) rate of 86% in 197 patients. Typical of APL, failure to enter CR resulted essentially exclusively from death, most often resulting from hemorrhage before CR could occur (“early death”). As is usual, early death was more frequent (42%v 6%) in patients with a WBC count greater than 10,000/L (hereafter high risk). Patients in CR continued receiving ATO, initially only for one 4-week course, but later, patients were given four such courses. With a median follow-up of 38 months of patients entering CR, 5-year disease-free survival (DFS) probability is 67% 4%, and 5-year overall survival (OS) probability is 64% 4% ( standard deviation). These rates will likely remain stable given that only one relapse was seen among 36 patients who were observed for more than 5 years. Patients given more than one consolidation course had a 5-year DFS of approximately 90% compared with the 5-year DFS of approximately 60% in patients given only one consolidation course; this observation appears somewhat self-fulfilling, given that patients had to remain in CR for more than 1 year to receive the third consolidation course and more than 2 years to receive the fourth. Recently, Mathews et al 3,4 in India administered ATO 10 mg daily until CR in 72 patients with newly diagnosed disease; 24% of these patients had a WBC count greater than 10,000/L, and most could not afford standard therapy. Eleven percent received one to two doses of an anthracycline during induction, but once in CR, patients received only ATO 10 mg each day for one month and then 10 days per month for 6 months. The CR rate was 86%; with a median follow-up of 5 years, DFS and OS probabilities were 80% 5% and 74% 5%, respectively. 4
Blockade of CD28/B7-2 Costimulation Inhibits Experimental Obliterative Bronchiolitis in Rat Tracheal Allografts
Authors: JUSSI  M. TIKKANEN, KARL B. LEMSTRÖM, PETRI K. KOSKINEN
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

T cell activation is a proximal event in the initiation of chronic rejection that may ultimately lead to obliterative bronchiolitis (OB) after lung transplantation. In addition to primary signals generated by the T cell receptor, T cell activation relies on costimulatory signals, of which the most important are mediated via interaction between CD28 and its ligands B7-1 and B7-2. In nontreated rat tracheal allografts, B7-2, but not B7-1, expression peaked 10 d after transplantation, unlike in syngeneic grafts, where no B7-2 upregulation was observed. Selective blockade of the CD28/B7-1 T cell costimulatory pathway by a mutant form of CTLA4Ig (cytotoxic T lymphocyte antigen 4 immunoglobulin), CTLA4IgY100F, did not affect epithelial injury or degree of luminal occlusion in rat tracheal allografts. Treatment with CTLA4Ig fusion protein, which blocks both CD28/B7-1 and CD28/B7-2 interaction, significantly delayed the development of epithelial injury and airway occlusion. Immunohistochemical analyses of allografts showed that selective inhibition of the CD28/B7-1 pathway did not affect cytokine expression. In contrast, treatment with CTLA4Ig was associated with a significant decrease in the intragraft production of tumor necrosis factor α , interleukin 2, and interferon γ , as well as slightly increased intragraft expression of interleukin 10. In conclusion, CTLA4Ig-mediated costimulatory blockade delays epithelial injury and attenuates obliterative changes and is associated with marked suppression of helper T cell type 1 (Th1)-dominated cytokine response. These observations emphasize the role of the CD28/B7-2 costimulatory pathway in regulating proinflammatory and Th1 cytokine responses and thereby in the development of epithelial and graft injury gradually leading to obliteration of the airway lumen.
The insulator factor CTCF controls MHC class II gene expression and is required for the formation of long-distance chromatin interactions
Authors: Parimal Majumder, Jorge A. Gomez, Brian P. Chadwick, Jeremy M. Boss
Journal: The Journal of Experimental Medicine (2008)

Knockdown of the insulator factor CCCTC binding factor (CTCF), which binds XL9, an intergenic element located between HLA-DRB1 and HLA-DQA1, was found to diminish expression of these genes. The mechanism involved interactions between CTCF and class II transactivator (CIITA), the master regulator of major histocompatibility complex class II (MHC-II) gene expression, and the formation of long-distance chromatin loops between XL9 and the proximal promoter regions of these MHC-II genes. The interactions were inducible and dependent on the activity of CIITA, regulatory factor X, and CTCF. RNA fluorescence in situ hybridizations show that both genes can be expressed simultaneously from the same chromosome. Collectively, the results suggest a model whereby both HLA-DRB1 and HLA-DQA1 loci can interact simultaneously with XL9, and describe a new regulatory mechanism for these MHC-II genes involving the alteration of the general chromatin conformation of the region and their regulation by CTCF.
Deletion and Translocation Involving Chromosome 3(p14) in Two Tumorigenic Kaposi's Sarcoma Cell Lines
Authors: Nicholas C. Popescu, Drazen B. Zimonjic, Sophie Leventon-Kriss, Joseph L. Bryant, Yanto Lunardi-Iskandar, Robert C. Gallo
Journal: JNCI Journal of the National Cancer Institute (1996)

Two neoplastic Kaposi's sarcoma (KS) cell lines, KS Y-1 (derived from a patient with KS associated with acquired immunodeficiency syndrome) and KS SLK (derived from an immunosuppressed patient with a renal transplant and KS or iatrogenic KS), have been shown to have abnormal chromosome constitution and to require no exogenous growth factors. They produce malignant tumors in immunodeficient mice. In contrast, all other cell cultures prepared in the past from KS specimens have shown to have normal diploid characteristics are hyperplastic, and depends on cytokines for growth, but they do not produce malignant tumors in immunodeficient mice.We investigated whether the chromosomal changes that occurred in these KS cell lines were random contribute to the pathogenesis of KS.We used the conventional G-banding technique and fluorescence in sti hybridization to identify structural and numerical chromosomal changes in the KS cell lines.We demonstrated that both cell lines are aneuploid and have some additional features in common, i.e., loss of copies of chromosomes 14 and 21 and nonrandom translocations and deletions in the short arm of chromosome 3 at region 3p14. These KS cell lines also exhibits loss of heterozygosity of loci at region 3p14-ter.This is the first time nonrandom chromosomal alterations have been described in KS neoplastic cells. On the basis of information available on other available on other cancers, the chromosome 3 alterations observed here can be expected to contribute to the neoplastic process in KS.Future research should focus on the identification cytogenetic markers, thus facilitating generation of specific molecular probes for detecting neoplastic cells early in the disease process.
Environmental Influences on Implanted Cardiac Pacemakers
Authors: M. Michaelson
Journal: JAMA (1971)

Cardiac pacemaker activity is subject to interference from a variety of electrical and radiofrequency fields. As new and more sensitive types of pacemakers are developed, the interference problem becomes more complex. Some potential sources of interference for implanted pacemaker systems include<sup>1</sup>radio frequency (RF) transmission such as radio and television broadcasting; RF energy from miscellaneous sources such as microwave ovens and radar; carrier current on power transmission lines; magnetic fields around power transformers and conductors carrying electric current; and arcing and sparking electrical equipment such as power tools, commutator motors, and ignition systems of aircraft, automobile, motorcycle, and lawnmowers. Medical equipment, such as diathermy, electrocautery, neurosurgical stimulators, and high-voltage radiation therapy units, are common sources of electrical interference within the hospital. The fixed-rate (asynchronous) pacemaker has a lowfrequency oscillator designed to deliver pulses at a desired cardiac stimulation rate. Once implanted, such units are fairly insensitive to electrical interference,
Mutations in Bone Morphogenetic Protein Type II Receptor Cause Dysregulation of Id Gene Expression in Pulmonary Artery Smooth Muscle Cells
Authors: Jun Yang, Rachel J. Davies, Mark Southwood, Lu Long, Xudong Yang, Anastasia Sobolewski, Paul D. Upton, Richard C. Trembath, Nicholas W. Morrell
Journal: Circulation Research (2008)

Heterozygous germ line mutations in the gene encoding the bone morphogenetic protein (BMP) type II receptor occur in more than 80% of patients with familial pulmonary arterial hypertension. Because inhibitors of DNA binding (Id) genes are major targets of BMP/Smad signaling, we studied the regulation of these transcription factors in pulmonary artery smooth muscle cells harboring mutations in BMP type II receptor and control cells. Mutant cells demonstrated a marked deficiency in BMP4-stimulated Id1 and Id2 gene and protein expression compared with control cells. Mutant cells were deficient in Smad1/5 signaling in response to BMPs but also in extracellular signal-regulated kinase (ERK)1/2 activation. We provide evidence for an important interaction between Smad1/5 and ERK1/2 signaling in the regulation of Id gene expression. Thus, BMP4-induced Id1 expression was negatively regulated by ERK1/2 activation. The mechanism involves ERK1/2-dependent phosphorylation of the Smad1 linker region (serine 206), which limits C-terminal serine 463/465 phosphorylation and inhibits Smad nuclear accumulation. Furthermore, activation of ERK1/2 by platelet-derived growth factor BB also caused Smad1 linker region phosphorylation and inhibited BMP4-induced Id1 gene expression. In contrast, Id2 expression was positively regulated by ERK1/2. Moreover, we show that both BMP type II receptor mutation and Id1 knockdown leads to loss of growth suppression by BMPs. Taken together, these findings indicate an important interaction between ERK1/2 and Smad1/5 in the regulation of Id genes. Platelet-derived growth factor, via ERK1/2, further impairs the deficiency in Smad signaling found in BMP type II receptor mutant cells. The integration of these signals at the level of Id gene expression may contribute to the pathogenesis of familial pulmonary arterial hypertension.
Getting More Performance from Performance Measurement
Authors: Christine K. Cassel, Patrick H. Conway, Suzanne F. Delbanco, Ashish K. Jha, Robert S. Saunders, Thomas H. Lee
Journal: New England Journal of Medicine (2014)

Interview with Dr. Christine Cassel on the lessons of past performance-measurement efforts and promising future directions. (13:33)Download Under today's performance-measurement paradigm, too many resources are invested in assessing too many activities that may not have major effects on patients' health. What can past successes and failures teach us about performance measures that effectively improve care?
The multidrug resistance phenotype confers immunological resistance.
Authors: J H Weisburg, M Curcio, P C Caron, G Raghu, E B Mechetner, P D Roepe, D A Scheinberg
Journal: The Journal of Experimental Medicine (1996)

Multidrug resistance (MDR), which is due, in part, to the overexpression of P-glycoprotein, confers resistance to a variety of natural product chemotherapeutic agents such as daunorubicin, vincristine, and colchicine. RV+ cells are a P-glycoprotein overexpressing variant of the HL60 myeloid leukemia cell line. In addition to classic MDR, RV+ cells displayed relative resistance to complement-mediated cytotoxicity with both immunoglobulin G and M antibodies against different cell surface antigens, but not to antibody-dependent cellular cytotoxicity and lymphokine-activated killing. Complement resistance was reversed both by treatment with verapamil and with specific monoclonal antibodies (mAbs) capable of binding to P-glycoprotein and blocking its function. To further confirm that the resistance of RV+ cells was not a consequence of the selection of the cells on vincristine, a second system involving P-glycoprotein infectants was also investigated. K562 cells infected with the MDR1 gene, which were never selected on chemotherapeutic drugs, also displayed relative resistance to complement-mediated cytotoxicity. This MDR1 infection-induced resistance was also reversed by mAbs that bind to P-glycoprotein. Therefore, the MDR phenotype as mediated by P-glycoprotein provides resistance to complement-mediated cytotoxicity. The increased intracellular pH and the decreased membrane potential due to the MDR phenotype may result in abnormal membrane attack complex function. This observation may have implications for the possible mechanisms of action of P-glycoprotein and for a possible physiologic role for P-glycoprotein in protection against complement-mediated autolysis.