tbuckley/cabot-search huggingface dataset:
Radiation effects in the lung.
Authors: J E Coggle, B E Lambert, S R Moores
Journal: Environmental Health Perspectives (1986)

This article outlines the principles of radiobiology that can explain the time of onset, duration, and severity of the complex reactions of the lung to ionizing radiation. These reactions have been assayed biochemically, cell kinetically, physiologically, and pathologically. Clinical and experimental data are used to describe the acute and late reactions of the lung to both external and internal radiation including pneumonitis, fibrosis and carcinogenesis. Acute radiation pneumonitis, which can be fatal, develops in both humans and animals within 6 months of exposure to doses greater than or equal to 8 Gy of low LET radiation. It is divisible into a latent period lasting up to 4 weeks; an exudative phase (3-8 weeks) and with an acute pneumonitic phase between 2 and 6 months. The latter is an inflammatory reaction with intra-alveolar and septal edema accompanied by epithelial and endothelial desquamation. The critical role of type II pneumonocytes is discussed. One favored hypothesis suggests that the primary response of the lung is an increase in microvascular permeability. The plasma proteins overwhelm the lymphatic and other drainage mechanisms and this elicits the secondary response of type II cell hyperplasia. This, in its turn, produces an excess of surfactant that ultimately causes the fall in compliance, abnormal gas exchange values, and even respiratory failure. The inflammatory early reaction may progress to chronic fibrosis. There is much evidence to suggest that pneumonitis is an epithelial reaction and some evidence to suggest that this early damage may not be predictive of late fibrosis. However, despite detailed work on collagen metabolism, the pathogenesis of radiation fibrosis remains unknown. The data on radiation-induced pulmonary cancer, both in man and experimental animals from both external and internal irradiation following the inhalation of both soluble and insoluble alpha and beta emitting radionuclides are reviewed. Emphasis is placed on the data showing that alpha emitters are at least an order of magnitude more hazardous than beta/gamma radiation and on recent data showing that the more homogeneous the irradiation of the lung, the greater is the carcinogenic hazard which contradicts the so-called "hot particle" theory.
Lower Osteopontin Plasma Levels Are Associated With Superior Outcomes in Advanced Non–Small-Cell Lung Cancer Patients Receiving Platinum-Based Chemotherapy: SWOG Study S0003
Authors: Philip C. Mack, Mary W. Redman, Kari Chansky, Stephen K. Williamson, Nichole C. Farneth, Primo N. Lara, Wilbur A. Franklin, Quynh-Thu Le, John J. Crowley, David R. Gandara
Journal: Journal of Clinical Oncology (2008)

S0003 was a phase III trial of carboplatin/paclitaxel with or without the hypoxic cytotoxin tirapazamine in patients with advanced or metastatic non-small-cell lung cancer (NSCLC). We investigated the relationship between clinical outcomes and plasma levels of the hypoxia-associated protein osteopontin (OPN) in patients on this protocol.Baseline plasma was obtained from 172 patients. In 56 patients, sequential plasma was obtained after one or two cycles. Concentrations of OPN, as well as plasminogen activator inhibitor-1 (PAI-1) and vascular endothelial growth factor (VEGF), were measured using enzyme-linked immunosorbent assay. Tumor expression of OPN was assessed by immunohistochemistry in 61 matched archival specimens.Patients with lower OPN levels (below the median) had a significantly superior overall survival compared with patients with higher levels, regardless of treatment arm (hazard ratio [HR] = 0.60, P = .002). A similar correlation was observed for progression-free survival (HR = 0.69, P = .02). When examined as a continuous variable, OPN maintained its significant association with both progression-free (HR = 1.05, P = .01) and overall survival (HR = 1.09, P < .0001). Patients with lower plasma OPN levels were significantly more likely to have tumor response (P = .03). No differences were observed between treatment arms. Tumor OPN levels did not correlate with patient outcomes or with plasma levels. No associations were observed between patient outcomes and VEGF or PAI-1 levels; however, plasma concentrations of these markers were significantly interrelated (P < .0001) and significantly decreased after treatment (P = .0002 and P = .03, respectively).Pretreatment plasma levels of OPN are significantly associated with patient response, progression-free survival, and overall survival in chemotherapy-treated patients with advanced NSCLC.
Long remission after lymphoblastic transformation of chronic granulocytic leukaemia.
Authors: M V Joyner, P Dujardin, J P Cassuto, P Audoly, M Schneider
Journal: BMJ (1978)

no support to the concept that a high-fibre diet is of value in maintaining clinical remission in patients with ulcerative colitis, although this does not exclude its value in patients who are particularly apt to develop rolonic obstruction with recurrence of disease activity.Most c. our patients tolerated the diet and at the end of the study many sa.d that they wished to continue with it in addition to sulphasalazine.
Phase I and pharmacokinetic study of karenitecin in patients with recurrent malignant gliomas
Authors: Stuart A. Grossman, Kathryn A. Carson, Surasak Phuphanich, Tracy Batchelor, David Peereboom, L. Burt Nabors, Glenn Lesser, Fredrick Hausheer, Jeffrey G. Supko
Journal: Neuro-Oncology (2008)

Karenitecin is a highly lipophilic camptothecin analogue with a lactone ring that is relatively resistant to inactivating hydrolysis under physiologic conditions. This phase I clinical trial was conducted to determine the maximum tolerated dose (MTD) of karenitecin in adults with recurrent malignant glioma (MG), to describe the effects of enzyme-inducing antiseizure drugs (EIASDs) on its pharmacokinetics, and to obtain preliminary evidence of activity. Karenitecin was administered intravenously over 60 min daily for 5 consecutive days every 3 weeks to adults with recurrent MG who had no more than one prior chemotherapy regimen. The continual reassessment method was used to escalate doses, beginning at 1.0 mg/m(2)/day, in patients stratified by EIASD use. Treatment was continued until disease progression or treatment-related dose-limiting toxicity (DLT). Plasma pharmacokinetics was determined for the first daily dose of karenitecin. Thirty-two patients (median age, 52 years; median KPS score, 90) were accrued. Seventy-eight percent had glioblastoma, and 22% had anaplastic glioma. DLT was reversible neutropenia or thrombocytopenia. The MTD was 2.0 mg/m(2) in daggerEIASD patients and 1.5 mg/m(2) in -EIASD patients. The mean (+/-SD) total body clearance of karenitecin was 15.9 +/- 9.6 liters/h/m(2) in daggerEIASD patients and 10.2 +/- 3.5 liters/h/m(2) in -EIASD patients (p = 0.02). No objective responses were observed in 11 patients treated at or above the MTD. The total body clearance of karenitecin is significantly enhanced by the concurrent administration of EIASDs. This schedule of karenitecin, a novel lipophilic camptothecin analogue, has little activity in recurrent MG.
ON THE PROPHYLAXIS OF CONTAGIOUS DISEASES IN A LARGE CITY.Read in the Section on State Medicine, at the Forty-fourth Annual Meeting of the American Medical Association.
Authors: SAMUEL P. DUFFIELD
Journal: JAMA (1893)

The above subject may seem to some who have not had charge of the department of contagious diseases of a large city, a very simple question. It will be found the most difficult problem that comes to the health officer for solution. An experience of six years as Health Officer of Detroit has most effectually changed many of my views on this subject, and what I now lay before you is the result of practical every-day efforts to reach the point of holding these diseases in check to the greatest degree possible. I am satisfied I have found a method, but as my Board has not indorsed it, it must slumber until some one proves that my views belong to the practical every-day realm and not to theory. I place before you a tabulated record of the contagious diseases, scarlatina and diphtheria, and will refer to it as I go
Abstract LB-289: Telomere length, genetic variants and gastroesophageal cancer risk: a case-control study in Chinese population
Authors: Jiangbo Du, Xun Zhu, Chen Zhu, Hongxia Ma, Zhibin Hu, Hongbing Shen, Guangfu Jin
Journal: Cancer Research (2014)

Abstract Backgrounds Telomeres are protective DNA-protein repeats structure at the extreme end of linear chromosomes that maintain chromosomal stability and integrity. Short telomere in peripheral blood leukocyte has been associated with an increased risk of multiple cancers. Moreover, heterogeneity of inter-individual telomere length is partly determined by hereditary factor. Recent genome-wide association studies (GWAS) have identified several telomere length related loci at 2p16.2 (ACYP2), 3q26 (TERC), 4q32.2 (NAF1), 5p15.33 (TERT), 10q24.33 (OBFC1), 19p12 (ZNF208) and 20q13.3 (RTEL1), some of which were also implicated with cancer risk. However, these findings were mainly observed in populations of European descent, and were not well demonstrated in other populations, especially for gastroesophageal cancer that is high incident in China but not in western countries. Design and Methods We measured relative telomere length (RTL) by quantitative real-time polymerase chain reaction in a Chinese case-control study including 1,136 gastric cancer cases, 1,045 esophageal cancer cases and 1,012 matched controls. Moreover, we performed genotyping by TaqMan assay for genetic variants at 2p16.2 (rs11125529), 3q26 (rs10936599), 4q32.2 (rs7675998), 5p15.33 (rs2736100, rs2736108), 10q24.33 (rs4387287), 19p12 (rs8105767), and 20q13.3 (rs755017). Results As compared with individuals in the fourth quintile of telomere length (i.e., moderately long telomeres), those with short telomeres were at an increased risk with ORs (95%CI) being 1.19 (0.92-1.55), 1.53 (1.19-1.98) and 3.00 (2.33-3.85) for the third, second and first quintiles, respectively. More interestingly, a significant elevated risk (OR= 1.54, 95%CI: 1.19-2.00) was also found in those at the fifth quintile with extreme long telomeres. We also confirmed that the G allele of rs2736100 at 5p15.33 exhibited a significant association with longer telomere length (r2= 0.106, P = 0.047), which, however, was not significantly associated with gastroesophageal cancer risk. We did not observe significant association of the other loci with telomere length or gastroesophageal cancer risk. Conclusions These findings suggest that either short or extreme long telomere may be risk factor for gastroesophageal cancer while telomere length related variants may be less important in the susceptibility to gastroesophageal cancer in Chinese population. Citation Format: Jiangbo Du, Xun Zhu, Chen Zhu, Hongxia Ma, Zhibin Hu, Hongbing Shen, Guangfu Jin. Telomere length, genetic variants and gastroesophageal cancer risk: a case-control study in Chinese population. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-289. doi:10.1158/1538-7445.AM2014-LB-289
Eyeblink conditioning in the infant rat: an animal model of learning in developmental neurotoxicology.
Authors: M E Stanton, J H Freeman
Journal: Environmental Health Perspectives (1994)

Classical conditioning of the eyeblink reflex is a relatively simple procedure for studying associative learning that was first developed for use with human subjects more than half a century ago. The use of this procedure in laboratory animals by psychologists and neuroscientists over the past 30 years has produced a powerful animal model for studying the behavioral and biological mechanisms of learning. As a result, eyeblink conditioning is beginning to be pursued as a very promising model for predicting and understanding human learning and memory disorders. Among the many advantages of this procedure are (a) the fact that it can be carried out in the same manner in both humans and laboratory animals; (b) the many ways in which it permits one to characterize changes in learning at the behavioral level; (c) the readiness with which hypotheses regarding the neurological basis of behavioral disorders can be formulated and tested; (d) the fact that it can be used in the same way across the life-span; and (e) its ability to distinguish, from normative groups, populations suffering from neurological conditions associated with impaired learning and memory, including those produced by exposure to neurotoxicants. In this article, we argue that these properties of eyeblink conditioning make it an excellent model system for studying early impairments of learning and memory in developmental neurotoxicology. We also review progress that has been made in our laboratory in developing a rodent model of infant eyeblink conditioning for this purpose.
Abstract 17: Preclinical and phase 1 trial results of JI-101, a novel, oral tyrosine kinase inhibitor that selectively targets VEGFR2, EphB4, and PDGFRβ
Authors: Mark Velleca, Linda Miller, Sunil Sharma, Michael Gordon, David Brittelli, Lisa Elkin, Raman Govindarajan, Udo Klein, Scott Mitchell, Nandhagopal N, Dapeng Qian, Xiaobing Qian, Thomas Stephen, Sreesha Srinivasa, Warren Stern
Journal: Cancer Research (2010)

Abstract Introduction JI-101 is a highly selective and potent angiogenesis inhibitor with unique EphB4 activity that distinguishes it from other agents in clinical development. We report the preclinical pharmacology and early clinical experience with this compound. Procedures Lead optimization was used to identify cgi1842 (now JI-101) with a targeted activity profile that is selective and unique. JI-101 was tested in binding, enzymatic, and cell-based assays for activity against kinase and non-kinase targets. Preclinical in vivo testing for PK, PD, efficacy, and safety pharmacology was performed in mouse, rat, guinea pig, and dog. A Phase I clinical trial is underway: 12 patients have been treated thus far with 28-day oral daily dosing at 100 mg, 200 mg, 400 mg QD or at 200 mg BID. PK, PD, and imaging analyses have been performed. Data JI-101 has a MW of 466D and high (&amp;lt;100 nm) potency against VEGFR2, EphB4, and PDGFR in enzymatic and cell-based assays. Broad kinase cross-screening (Ambit KinomeScan, 445 kinases) reveals that JI-101 is highly selective for angiogenic kinases with only 23 kinases demonstrating a Kd 15). JI-101 was co-administered with paclitaxel in a MDA-MB-231 mouse xenotransplant model, resulting in greater efficacy and no increased toxicity. Based on 28-day GLP toxicology studies conducted in rat and dog, a 100 mg qd starting dose (2 × 50 mg capsules) was chosen for Phase I studies. JI-101 appears to be very well-tolerated to date with no dose limiting toxicities. Patients have received 1-9 cycles with most receiving multiple cycles and 5 remain on study at 100 mg (1 pt), 200 mg (1 pt), and 400 mg (3 pt). Manageable hypertension has been seen in all cohorts indicating a possible PD effect. Hand-foot syndrome of short duration was seen at the 400mg dose level. Further clinical details of the PK, PD, tolerability and efficacy of JI-101 will be presented. Conclusions JI-101 potently inhibits 3 critical angiogenic kinases (VEGFR2, EphB4, and PDGFR) and is the only such “triple” angiogenesis inhibitor currently in development. JI-101 shows robust preclinical and clinical pharmacology and is well-tolerated to date in human trials. In tumors where EphB4 may play an oncogenic role, such as head and neck cancer, JI-101 may have anti-proliferative effects in addition to anti-angiogenic effects and should be amenable to combination therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 17.
β‐Globin gene cluster haplotypes in sickle cell patients from southwest Iran
Authors: Z. Rahimi, M. Karimi, M. Haghshenass, A. Merat
Journal: American Journal of Hematology (2003)

Abstract Sickle cell anemia in Iran is accompanied by a high level of HbF and mild clinical presentation. Here we report haplotypes of the β gene cluster found in 81 randomly selected sickle cell patients, including 47 sickle cell anemia (SS), 17 sickle cell trait (AS), and 17 sickle/thalassemia (S/thal) from southwest Iran. We found all five common typical haplotypes as well as five atypical haplotypes in our patients. Except for four patients with homozygous Benin haplotype, none of the other African typical haplotypes were found in a homozygous state. Arab‐Indian was found to be the most prevalent haplotype in the study population. This haplotype accounted for 51.1% as the homozygous form in SS patients, where 69.1% of chromosomes in these patients had the Arab‐Indian haplotype. Bantu A2 was the second most prevalent haplotype among all patients. The mean %HbF in SS patients was 27.83 and in the homozygous Arab‐Indian haplotype it was still higher (30.40%), while in AS patients the %HbF was only 1.20. The high %Gγ chain (71.81) in the Arab‐Indian homozygous haplotype was concomitant with the presence of an Xmn I site in both chromosomes. The presence of the Arab‐Indian haplotype as the predominant haplotype might be suggestive of a gene flow to/from Saudi Arabia or India. More haplotype investigations of a normal population can clarify the high incidence of Bantu A2 haplotype in our population. Am. J. Hematol. 74:156–160, 2003. © 2003 Wiley‐Liss, Inc.
Synergistic disaggregation of platelets by tissue-type plasminogen activator, prostaglandin E1, and nitroglycerin.
Authors: J S Stamler, D E Vaughan, J Loscalzo
Journal: Circulation Research (1989)

Endothelial cells produce at least three substances that can attenuate the platelet aggregation response: tissue-type plasminogen activator; the platelet inhibitory prostaglandins I2 and E1; and endothelium-derived relaxing factor, one form of which exhibits properties of nitric oxide. Since platelet aggregates formed in vivo are involved in the initiation of many clinically important occlusive vascular syndromes, we tested the hypothesis that these endothelial products act synergistically to disperse platelet aggregates. Our data reveal that tissue-type plasminogen activator, prostaglandin E1, and nitroglycerin (an organic nitrate activator of guanylate cyclase analogous to endothelium-derived relaxing factor) act synergistically to disaggregate platelets and do so in part by modulation of platelet cyclic nucleotides. These data suggest a potential mechanism by which the endothelium protects against the formation of platelet aggregates in vivo and offer a potential strategy for improving the efficacy of thrombolytic therapy.
Induced sputum: time from expectoration to processing
Authors: A. Efthimiadis, L. Jayaram, S. Weston, S. Carruthers, F.E. Hargreave
Journal: European Respiratory Journal (2002)

One of the limitations in the use of induced sputum to measure indices of airway inflammation is the perceived need to process the sample within 2 h. Therefore, the authors investigated whether the processing of induced sputum could be delayed. Induced sputum samples obtained from asthmatic subjects (n=30) were examined. Each sample was stored at 4°C. A portion was selected and processed within 2 h and the remaining expectorate (sputum plus saliva) was refrigerated. Later an equal amount was selected and processed at either 9 (n=15) or 18 (n=15) h. The sputum was examined for cell counts and viability, fluid-phase eosinophil cationic protein (ECP), interleukin‐8 (IL‐8) and fibrinogen. Repeatability of measurements was assessed by the interclass correlation coefficient (ICC). Measurements obtained at 9 h did not differ from those made at 2 h and the repeatability was excellent (ICC 0.88–0.99). However, by 18 h the median cell viability was reduced from 65.0% to 43.0% and the ICC was generally lower: 0.10 for total cell count, 0.24 for viability, 0.60 for neutrophils, 0.90 for eosinophils, 0.56 for macrophages, 0.76 for ECP, 0.82 for IL‐8 and 0.84 for fibrinogen. The results indicate that when induced sputum from subjects with asthma is kept at 4°C, examination of cell counts can be delayed for ⩽9 h and for the fluid-phase indices measured for ⩽18 h. Further investigation of this issue is required for spontaneous sputum, other airway diseases and other inflammatory markers.
Improving State Pain Policies: Recent Progress and Continuing Opportunities
Authors: A. M. Gilson, D. E. Joranson, M. A. Maurer
Journal: CA A Cancer Journal for Clinicians (2007)

The National Institutes of Health reports that 100 million Americans suffer from chronic pain, including pain associated with the disease of cancer. Painful conditions can strike anyone, including cancer patients and cancer survivors. Unrelieved severe pain can limit a person's functioning and sometimes even destroy the will to live. When the quality of pain relief provided is inadequate, it is usually the result of failures to apply existing knowledge about pain and its treatment, including the appropriate use of opioids. But pain relief also can be affected by the regulatory environment and fear of being investigated for excessive prescribing. The importance of evaluating and improving policies governing pain management has been recognized by national and international authorities, including the Institute of Medicine and the World Health Organization. A pilot examination of state laws and regulatory policies demonstrated that they contained a number of outdated medical concepts and prescribing restrictions and did not contain key elements of law that can make pain management a priority for licensed medical practitioners. The Pain & Policy Studies Group developed a research program to evaluate US federal and state policy governing the medical use of pain medication. This article describes 3 national policy evaluations and how the results are being used to document improvements in state pain policies. An emerging role for clinicians and their professional organizations to improve their state's pain policies is discussed.
Tetanus after Head Injury in an Immunized Subject
Authors: W. Lewin
Journal: BMJ (1944)

TETANUS AFTER HEAD INJURYM:IA 3PLelsewhere in the country.This may be regarded as fortunate in view of the wide dispersal of other passengers and the crew of tlle ship. SummaryA case of typhus fever occurring in this country is described.The importance of including typhus fever in the differential diagnosis of pyrexia of uncertain origin is stressed.
Effect of Otostegia persica extraction on renal injury induced by hindlimb ischemia-reperfusion: A rat model
Authors: Mohammad Ashrafzadeh Takhtfooladi, Hamed Ashrafzadeh Takhtfooladi, Fariborz Moayer, Poorya Karimi, Hesam Abbasian Asl
Journal: International Journal of Surgery (2014)
Germline ETV6 mutations in familial thrombocytopenia and hematologic malignancy
Authors: Michael Y Zhang, Jane E Churpek, Siobán B Keel, Tom Walsh, Ming K Lee, Keith R Loeb, Suleyman Gulsuner, Colin C Pritchard, Marilyn Sanchez-Bonilla, Jeffrey J Delrow, Ryan S Basom, Melissa Forouhar, Boglarka Gyurkocza, Bradford S Schwartz, Barbara Neistadt, Rafael Marquez, Christopher J Mariani, Scott A Coats, Inga Hofmann, R Coleman Lindsley, David A Williams, Janis L Abkowitz, Marshall S Horwitz, Mary-Claire King, Lucy A Godley, Akiko Shimamura
Journal: Nature Genetics (2015)