tbuckley/cabot-search huggingface dataset:
Mutations of the p53 Gene as a Predictor of Poor Prognosis in Patients With Non-Small-Cell Lung Cancer
Authors: T. Mitsudomi, T. Oyama, T. Kusano, T. Osaki, R. Nakanishi, T. Shirakusa
Journal: JNCI Journal of the National Cancer Institute (1993)

Background: Inactivation of the p53 tumor suppressor gene (also known as TP53) through a point mutation and/or loss of heterozygosity is one of the most common genetic changes found in various types of human tumors. Purpose : Our purpose was to investigate the relationship between the presence of p53 gene mutations and survival of patients with non-small-cell lung cancer (NSCLC) of all stages who underwent surgery with preoperative curative intent as a routine therapeutic intervention. The prognostic significance of factors like sex, age, tumor histology, and the stage of the disease was also evaluated. Methods : We analyzed 120 tumor specimens from patients with histologically confirmed NSCLC for p53 mutations occurring in exons 5 through 8 by polymerase chain reaction-single-strand conformation polymorphism assay of genomic DNA. Univariate and multivariate analyses were performed to assess the association between p53 mutations and the survival of the NSCLC patients. Results : Fifty-one (43%) of 120 tumor specimens showed p53 mutations. Overall, the p53 mutations did not correlate with sex, age, or the clinical stage of the disease but showed frequent association with tumors of squamous cell histology. Univariate analysis revealed that the patients with p53 mutations survived for a significantly shorter period of time after surgery than those without the mutations ( P =.0100, logrank test). The presence of p53 mutations was a significant prognostic factor in the patients with advanced disease (stages IIIA through IV) ( P =.0091) but not in those with early disease (stages I and II) ( P =.2837). Multivariate analysis using the Cox proportional hazards model found independent prognostic significance for p53 mutations (hazards ratio [HR] = 1.84; P =.018) and advanced disease stage (HR = 2.20; P =.003). The model also predicted the lower risk for female patients (HR = 0.51; P =.040). Conclusion : The occurrence of p53 mutations in some NSCLC tumors may be independently associated with a shortened overall survival and may be of somewhat more prognostic significance in patients with advanced stage than in those with early stage of the disease. Implication : Detection of p53 mutations may help in the selection of NSCLC patients suitable for appropriate investigational therapeutic strategies in view of improving their survival and quality of life. [J Natl Cancer Inst 85:2018–2023, 1993]
Transforming growth factor-beta. Multiple actions and potential clinical applications
Authors: M. B. Sporn
Journal: JAMA (1989)

THE CURRENT excitement in research on transforming growth factor—β (TGF-β) comes from its multiple actions on almost every type of cell and its potential for therapeutic use in common clinical conditions for which there are no adequate pharmacologic agents. Although TGF-β was identified originally in an assay that measured its ability to enhance the growth of fibroblasts in soft agar (transformation), its true importance is as a mediator of normal cellular physiology, in particular during normal formation of tissues (as in embryogenesis) and during tissue response to injury (as in inflammation and repair). Almost all cells have been shown to make TGF-β in one of its molecular forms, and al— most all normal cells have receptors for TGF-β.  Transforming growth factor—β1 is a highly stable peptide that consists of two identical chains, each containing 112 amino acids. It was first isolated and characterized from human platelets and placentas as well
THE EXPERIMENTAL PRODUCTION OF NECROSIS OF THE LIVER IN THE GUINEA PIG
Authors: Moyer S. Fleisher, Leo Loeb
Journal: The Journal of Experimental Medicine (1914)

Through the intravenous injection of various substances differing very much in character, multiple necrosis can be produced in the liver of the guinea pig. In the mouse the effect of these substances is absent or much less marked. Different substances seem to differ, however, in their power to produce necrosis. In control animals necrosis in the liver is much more rare. It is found especially in animals subjected to various injurious influences. The necrotic areas are usually situated between the portal and central areas of the liver acini. Their development is not due to thromboses interfering with the circulation in certain areas of the liver. They are probably due to a weakening of the circulation in the liver or to interference with the metabolism of the cells as a result of the injection of foreign substances. Mechanical factors (pressure on the liver cells) may have an additional effect. This necrosis may be compared etiologically to the acute gastric ulcers which can be produced through a great variety of toxic substances in the guinea pig.
The Drug Treatment of Depression
Authors: Jerome Motto
Journal: JAMA (1970)

<h3>To the Editor.—</h3> I welcome the comments of my colleagues but regret that they offer no specific data in their letter. The assertion that current data on antidepressants demonstrate their efficacy is open to question. Cole<sup>1</sup>states that after seven years of experience with antidepressants "their place in the physicians' armamentarium is far from clear" and that "the differences between the efficacy of the drug and a placebo have not been as great as one might wish." Klein and Davis<sup>3</sup>list 25 controlled comparisons of imipramine and placebo imipramine is found superior in 7, questionable in 13, and equal to placebo in 5. Kalinowski and Hippius<sup>4</sup>caution that while published figures reflect the optimal potential of these drugs, "in actual practice other considerations often arise," that4 "agitated depressions respond poorly or not at all," that those depressions with "much neurotic symptomatology or hypochrondriasis give poor results," and
Assessing the Cure of the Zollinger-Ellison Syndrome after Gastrinoma Resection
Authors: David C. Metz
Journal: Annals of Internal Medicine (1994)

Letters15 January 1994Assessing the Cure of the Zollinger-Ellison Syndrome after Gastrinoma ResectionDavid C. Metz, MD, Vitaly A. Fishbeyn, MD, and Robert T. Jensen, MDDavid C. Metz, MDNational Institute of Diabetes and Digestive and Kidney Diseases; Bethesda, MDSearch for more papers by this author, Vitaly A. Fishbeyn, MDNational Institute of Diabetes and Digestive and Kidney Diseases; Bethesda, MDSearch for more papers by this author, and Robert T. Jensen, MDNational Institute of Diabetes and Digestive and Kidney Diseases; Bethesda, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-120-2-199401150-00013 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Dr. Hammami questions whether the immediate postoperative evaluation before discharge is of any clinical utility and can be omitted. We agree that the 3- to 6-month evaluation is more important because it allows recovery from the immediate postoperative period and therefore may have greater predictive value and is preferred if a single evaluation is done.We continue to recommend the immediate postoperative evaluation. Although we do not discontinue gastric antisecretory therapy if the postoperative fasting gastrin and secretin test results are normal, these results influence our approach to patients at the 3- to 6-month evaluation. If the patient ...References1. Pisegna JR, Norton JA, Slimak GG, Metz DC, Maton PN, Jensen RT. Effects of curative resection on gastric secretory function and antisecretory drug requirement in the Zollinger-Ellison syndrome. Gastroenterology. 1992; 102:767-78. Google Scholar2. Metz DC, Pisegna JR, Fishbeyn VA, Benya RV, Jensen RT. Control of gastric acid hypersecretion in the management of patients with Zollinger-Ellison syndrome. World J Surg. 1993; 17:468-80. Google Scholar Author, Article, and Disclosure InformationAffiliations: National Institute of Diabetes and Digestive and Kidney Diseases; Bethesda, MD PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 January 1994Volume 120, Issue 2Page: 165KeywordsAchlorhydriaDrug therapyDrugsGastrinHospitalizationsSecretinZollinger Ellison syndrome Issue Published: 15 January 1994 CopyrightCopyright © 1994 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Methylene Blue Improves the Hepatopulmonary Syndrome
Authors: Peter Schenk
Journal: Annals of Internal Medicine (2000)

The hypoxemia of the hepatopulmonary syndrome, seen in patients with severe chronic liver dysfunction, results from widespread pulmonary vasodilation. No established drug therapy is available for this condition.To study the effect of methylene blue, a potent inhibitor of guanylate cyclase, in patients with severe hepatopulmonary syndrome.Open, uncontrolled trial.Medical intensive care unit at the university hospital in Vienna, Austria.7 patients with advanced cirrhosis and severe hepatopulmonary syndrome with PaO(2) of 60 mm Hg or less.Insertion of a pulmonary artery catheter and an arterial indwelling catheter; intravenous administration of methylene blue, 3 mg/kg of body weight, over a 15-minute period.Serial measurements of gas exchange and hemodynamic variables.After methylene blue administration, PaO(2) increased in all patients (from a baseline mean +/- SD of 58 +/- 2.5 mm Hg to 74 +/- 11.5 mm Hg 5 hours after infusion; P = 0.006) and the alveolar-arterial difference for partial pressure of oxygen (PAO(2) - PaO(2) ) decreased in all patients, with a maximum effect achieved after 5 hours (from 49 +/- 3.3 mm Hg to 30 +/- 10.4 mm Hg; P = 0.003); even after 10 hours, PAO(2) - PaO(2) was still significantly reduced compared with baseline (P = 0.041). Oxygenation improved because of reduction in shunt fraction (from 41% +/- 3.1% to 25% +/- 4.5%; P < 0.001). Mean pulmonary artery pressure increased (from 20 +/- 5.2 mm Hg to 23 +/- 3.6 mm Hg; P = 0. 028), as did pulmonary vascular resistance (from 58 +/- 23 dyne/sec. cm(-5) to 115 +/- 56 dyne/sec. cm(-5); P = 0.012). Arterial blood pressure did not change significantly. Cardiac output decreased (from 10.6 +/- 2.2 L/min to 8.6 +/- 2.7 L/min; P = 0.008) and systemic vascular resistance increased (from 527 +/- 144 dyne/sec. cm(-5) to 729 +/- 222 dyne/sec. cm(-5); P = 0.037). Heart rate, central venous pressure, and pulmonary capillary wedge pressure remained unchanged.Intravenous methylene blue improved hypoxemia and hyperdynamic circulation in patients with liver cirrhosis and severe hepatopulmonary syndrome.
Tubes for Tracheostomy
Authors: Hubert J. Adler
Journal: JAMA (1963)

ABSTRACT To the Editor: —Concerning the article by Epstein et al on tracheostomy (JAMA183:966 [March 16] 1963), new, flexible, plastic trach  can be cut to any desired length on the operating table. The flexibility of these tubes lessens the trauma to the tracheal wall and there is less drying of the mucus inside the tube. If the procedure is properly supervised, there is no need for an inner tube.
Clinical utility of the anti-CCP assay in patients with rheumatic diseases
Authors: D M Lee
Journal: Annals of the Rheumatic Diseases (2003)

To determine the frequency of antibodies to cyclic citrullinated peptides (CCP) in a group of patients with a diversity of rheumatic diseases.249 consecutive sera from an arthritis clinic sent for rheumatology testing were selected for testing with the anti-CCP2 assays and for the presence of rheumatoid factor (RF). Patient charts were reviewed for demographic information, clinical diagnosis, radiographic information, and other laboratory data.The sensitivity and specificity of anti-CCP reactivity for the diagnosis of rheumatoid arthritis (RA) were 66.0% and 90.4%, respectively. This compared with the sensitivity and specificity of RF for RA at 71.6% and 80.3%. Furthermore, 10/29 (34%) RF- patients with RA demonstrated reactivity to CCP. The presence of either anti-CCP or RF increased testing sensitivity for diagnosis of RA to 81.4%; the presence of both RF and anti-CCP demonstrated a testing specificity similar to that of anti-CCP reactivity alone for the diagnosis of RA (91.1%).The detection of anti-CCP is useful for the diagnosis of RA, in fact even more so than RF, because of its higher specificity.
Superoxide production by phagocytic leukocytes.
Authors: D B Drath, M L Karnovsky
Journal: The Journal of Experimental Medicine (1975)

Mononuclear phagocytic leukocytes, as well as polymorphonuclear leukocytes, produce and release superoxide at rest, and this is stimulated by phagocytosis. Of the mouse monocytic cells studied, alveolar macrophages released the largest amounts of superoxide during phagocytosis, followed by normal peritoneal macrophages. Casein-elicited and "activated" macrophages released smaller quantities. In the guinea pig, polymorphonuclear leukocytes and casein-elicited macrophages were shown to release superoxide during phagocytosis whereas alveolar macrophages did not. Superoxide release accounted for only a small fraction of the respiratory burst of phagocytosis in all but the normal mouse peritoneal macrophage, the guinea pig polymorphonuclear leukocyte, and probably the mouse alveolar macrophage. There are obviously considerable species differences in O2-release by various leukocytes that might reflect both the production and/or destruction (e.g. by dismutase) of that substance.
Acute Poisoning with Potassium Bichromate
Authors: C. N. Partington
Journal: BMJ (1950)

FIO. 5.-Same fracture as mn Fig. 4 three months after operation.category; one had rheumatoid arthritis and the other was 88 years of age.Some cases classed as fair on account of shortening had excellent function; one such patient walked 8 miles at the age of 62.In Table V comparison is made with results obtained by other workers.TABLE IV.-Final Assessment in 28 Surviving Cases Result Cases Remarkcs _~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~.
Successful retrograde and antegrade passage of narrow and complete pancreatic strictures using a cystogastrostome
Authors: E. Kim, T. Aouattah, P. Deprez
Journal: Endoscopy (2011)

Pancreatic duct strictures may be due to acute or chronic pancreatitis, pancreatic neoplasms, or anastomotic stenosis. Some of these strictures may be almost complete and only traversable with hydrophilic guide wires. When the passage of tapered catheters, Soehendra or balloon dilators is not possible, appropriate endoscopic drainage of the pancreatic duct may fail. Blind passage of a needle knife [1] or endoscopic ultrasound (EUS)-guided antegrade drainage may be helpful [2] [3] [4].
P236Evaluation of safety and feasibility of Mybpc3 gene therapy in a mouse model of hypertrophic cardiomyopathy
Authors: G Mearini, D Simpel, B Geertz, L Kraemer, S Schlossarek, F Weinberger, O Mueller, T Voit, T Eschenhagen, L Carrier
Journal: Cardiovascular Research (2014)

Purpose: Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular hypertrophy (LVH) and diastolic dysfunction, and is frequently caused by MYBPC3 mutations, which mainly result in haploinsufficiency of cardiac myosin-binding protein C (cMyBP-C). We recently provided proof-of-concept studies that adeno-associated virus (AAV)-mediated RNA-based therapies (exon skipping and trans-splicing) remove the mutation in a homozygous Mybpc3-targeted knock-in (KI) mouse model of HCM. However, the level of cMyBP-C remained low. In the present study, we evaluated the feasibility and safety of Mybpc3 gene therapy to correct cMyBP-C protein haploinsufficiency and prevent the cardiac phenotype in KI mice. Methods: FLAG-tagged Mybpc3 cDNA under the control of the human TNNT2 promoter was packaged in AAV9. Different doses of AAV9 (10^11, 3x10^11, 10^12, 3x10^12 viral genome (Vg)/mouse) or PBS were administered in the temporal vein of 1-day-old KI mice. Cardiac function was analyzed at different postnatal times until 34 wks by echocardiography and compared to age-matched wild-type (WT) mice. Levels of cMyBP-C protein were determined by Western blot and localization of transgenic protein was evaluated by immunofluorescence with specific antibodies in cardiac sections. Results: KI mice did not show a cardiac phenotype at postnatal day 1 (P1), but exhibited reduced fractional area shortening (FAS) at P2 and LVH at P3. AAV9-mediated Mybpc3 gene transfer dose-dependently and partially prevented the reduction of FAS and increase in LVM/BW ratio over time. In particular, doses of 10^12 and of 3x10^12 Vg/mouse fully prevented the development of cardiac dysfunction and hypertrophy 24 wks post-administration, respectively. The amount of FLAG-cMyBP-C and therefore of total-cMyBP-C was dose-dependently increased in ventricular tissue of AAV9-FLAG-Mybpc3-treated mice. FLAG-cMyBP-C protein was restricted to the heart and was not found in liver and skeletal muscle. In addition, immunofluorescence of cardiac sections showed the classical sarcomere striation pattern of cMyBP-C as doublet in the A-band. Conclusions: This study provides proof-of-principle of gene therapy as a feasible treatment for HCM associated with MYBPC3 mutation. This therapeutic strategy is particularly attractive for severe forms of HCM affecting children.
Effectiveness of a Mass Immunization Campaign Against Serogroup C Meningococcal Disease in Quebec
Authors: Philippe De Wals
Journal: JAMA (2001)

Context An outbreak of meningococcal disease in Quebec province prompted a mass immunization program.The impact of this campaign on the epidemiology of meningococcal disease has not been studied. ObjectivesTo study the impact of a mass immunization campaign using polysaccharide vaccine on the epidemiology of meningococcal disease (MCD) and to assess serogroup C vaccine effectiveness (VE).Design, Setting, and Subjects Analysis of MCD cases reported in Quebec from 1990 to 1998, before and after the mass immunization campaign was conducted during the winter of 1992-1993, when 84% of residents aged 6 months to 20 years (the target population, approximately 1.9 million individuals) were vaccinated. Main Outcome MeasuresIncidence of MCD in 1990-1998; incidence of cultureproven serogroup C MCD between April 1, 1993, and March 31, 1998, compared among vaccinated and unvaccinated persons in the target population. ResultsThe incidence of serogroup C disease decreased after the mass immunization campaign, from 1.4 per 100 000 in 1990-1992 to 0.3 per 100 000 in 1993-1998, and the overall incidence of other serogroups remained stable at 0.7 per 100000, with a small increase in the proportion of cases caused by serogroup Y (P = .009).Protection from serogroup C MCD was indicated in the first 2 years after vaccine administration (VE, 65%; 95% confidence interval [CI], 20%-84%), but not in the next 3 years (VE, 0%; 95% CI, -5% to 65%).Vaccine effectiveness was strongly related to age at vaccination: 83% (95% CI, 39%-96%) for ages 15 through 20 years, 75% (95% CI, -17% to 93%) for ages 10 through 14 years, and 41% (95% CI, -106% to 79%) for ages 2 through 9 years.There was no evidence of protection in children younger than 2 years; all 8 MCD cases in this age group occurred in vaccinees.Conclusions Serogroup C polysaccharide vaccine is effective for controlling outbreaks in teenaged individuals but should not be used in children younger than 2 years.The mass campaign did not induce significant serogroup switching.
Enhanced activity of hormone-sensitive adenylate cyclase during dietary restriction in the rat: dependence on age and relation to cell size.
Authors: B Cooper, F Weinblatt, R I Gregerman
Journal: Journal of Clinical Investigation (1977)

Age-related decreases of hormone-sensitive adenylate cyclase activities of rat fat cell plasma membranes (ghosts) have been recently described. Glucagon-sensitive activity was completely lost between 1 and 6 mo, an interval in which fat cell size increases rapidly, while decreased activation by ACTH was gradual over the entire life span of the animal (24 mo), and epinephrine-sensitive enzyme diminished modestly and only during senescence. In the present studies an attempt was made by restricting food intake to assess the importance of changing cell size in the age-related alterations of hormone-sensitive enzyme activities. Enzyme activities were determined before restriction and at monthly intervals for 3 mo for the unstimulated enzyme (basal) and in the presence of maximally stimulating concentrations of glucagon, ACTH, epinephrine, and fluoride. Activities were calculated per milligram ghost protein or per cell. Restriction of food intake for 3 mo starting at 1 or 12 mo produced fat cells equal in size to those of 5-wk-old animals fed ad lib. In young animals restricted for 1 mo, hormone-stimulated activity expressed as fold increase (stimulated/basal) was not merely maintained as the cells were prevented from enlarging, but was enhanced two to three times over the initial values with all three hormones. With continued restriction epinephrine-sensitive activity remained two times increased. Glucagon and ACTH responses subsequently decreased, but even by 3 mo of restriction, responses to the latter hormones, although declining, were still 1.5-3 times greater than the unrestricted controls, regardless of whether activity was expressed as total activity per milligram ghost protein or per cell, or as fold-increase. In the young animals, basal and fluoride-sensitive activities after a 3-mo restriction were unchanged or had decreased only slightly, depending on the base line used. Dietary restriction of adult animals for 3 mo, in contrast to the results in the young, did not increase total hormone-stimulated activity but rather produced either 0% (per milligram protein) or 25% decrease (per cell) for epinephrine-sensitive enzyme, 25 or 50% decrease of ACTH response, and 40 or 60% decreases of basal- and fluoride-stimulated activities. Expression of activities of restricted adults as fold-increase (stimulate/basal) showed an "increase of responsiveness" for all three hormones, but this was a reflection of the marked decrease of basal activity. Nonetheless, the restricted adults showed significant restoration of a small amount of glucagon-sensitive activity (1.8-fold over basal). These results indicate that cell size, per se, is not a dominant factor affecting hormone-responsive adenylate cyclase under conditions of dietary restriction...