tbuckley/cabot-search huggingface dataset:
Hormonal Regulation of Pulmonary Surfactant
Authors: PHILIP L. BALLARD
Journal: Endocrine Reviews (1989)

THE LUNGS of mammals and many other vertebrates contain surface active material in the peripheral air spaces. This material, comprised of various lipids and proteins, gives rise to a phospholipid monolayer which lines lung alveoli. The lipid monolayer stabilizes alveoli at low lung volumes, preventing collapse and allowing for normal respiration. A developmental deficiency of pulmonary surfactant in infants who are born prematurely results in respiratory distress syndrome (hyaline membrane disease) of the newborn infant. This disease is characterized by progressive atelectasis, inadequate oxygenation, and eventual respiratory failure, and it is the major cause of morbidity and mortality in premature infants. Regulation of lung development during fetal life has been studied extensively since 1969. In that year, Liggins (1) first demonstrated a stimulatory effect of dexamethasone infusion on lung aeration in prematurely delivered lambs. His pioneering observations have been confirmed by many investigators (reviewed in Ref. 2), and it is now established that glucocorticoid treatment of the fetus accelerates most, if not all, aspects of lung development. In addition, several other hormones are now known to either stimulate or inhibit pulmonary differentiation.
The TRAIL to an anti-cancer agent
Authors: Wafik S. El-Deiry
Journal: Drug Resistance Updates (1999)

ell death receptors such as Fas/APO1/CD95 or the Tumor Necrosis Factor Receptor#1 (TNFR1) are potent inducers of apoptosis once overexpressed or engaged by their respective ligands Fas or Tumor Necrosis Factor (TNF) (see 1 and 2 for review).As systemic agents for cancer therapy, however, Fas and TNF have major limitations that have kept them out of the clinical armamentarium, namely side effects due to their lack of specificity for killing cancer cells. The TNF-related apoptosis-inducing ligand (TRAIL) is an exciting newcomer because it appears to specifically kill transformed and cancer cells but not normal cells (Fig. 1). Clues as to why TRAIL does not kill normal cells began to surface in 1997 when two TRAIL decoy receptors (TRID, Truncated Intracellular Domain, and TRUNDD, Truncated Death Domain) were cloned. These decoys were found to be expressed more on normal as compared to cancer cells and suggested to bind and compete away TRAIL from binding its two proapoptotic signaling receptors (DR4 and KILLER/DR5). Because of its promise, work has rapidly progressed to determine the feasibility and potential safety of bringing TRAIL into clinical trials. In the February 1999 issue of Nature Medicine, the group at Immunex Corporation led by David H.Lynch presents evidence for the safety and potential efficacy of TRAIL therapy against breast cancer in a Severe Combined Immunodeficiency (SCID) mouse model. They generated a recombinant molecule that has a modified leucine zipper (LZ) fused to either murine or human TRAIL (LZ-TRAIL).The leucine zipper permits trimerization of the soluble TRAIL cytokine which is believed to enhance its biological effects. In cell culture, the human LZ-TRAIL had no toxicity towards human mammary epithelial cells, human renal proximal tubule epithelial cells, normal human lung fibroblasts, or human skeletal muscle cells while demonstrating toxicity towards MDA-231 mammary adenocarcinoma cells at concentrations greater than 10 ng/ml LZ-TRAIL. Interestingly, LZ-TRAIL displayed a similar toxicity towards normal human astrocytes in culture. Intravenous injection of 200 μg of human LZ-TRAIL had no reported toxicity up to 24 h as assessed by observation and hematoxylin and eosin staining of liver and brain, whereas mice that received 50 μg of human LZ-CD95L (leucine zipper-Fas ligand fusion protein) were moribund within 55 min due to massive hepatocellular degeneration, necrosis and hemorrhage. Systemic administration of LZ-TRAIL twice daily for 10 days after intraperitoneal inoculation of CB17-SCID mice with 10 million MDA-231 breast cancer cells prolonged survival (all control mice were dead by 40–50 days whereas in C
Pernicious anaemia among Asians in Singapore.
Authors: F. J. Jayaratnam, C. S. Seah, J. L. Da Costa, K. K. Tan, W. O'Brien
Journal: BMJ (1967)

In an investigation of 40 consecutive cases of megaloblastic anaemia admitted to the Medical Unit, Thomson Road General Hospital, Singapore, from mid-1962 until the end of 1965, six patients (four Chinese and two Indians) were found to fulfil all the criteria for a diagnosis of pernicious anaemia. All six had megaloblastic marrows, histamine-fast (maximal stimulation) achlorhydria, very low serum vitamin-B12 levels, and an inability to absorb this vitamin orally, this inability being corrected by the addition of intrinsic factor. These cases are worth reporting, because pernicious anaemia has not hitherto been reported in Singapore and Malaysia, and also because of the paucity of reports of pernicious anaemia in Chinese and Indians.
Thrombocytopenia and Minoxidil
Authors: STEVEN J. PEITZMAN
Journal: Annals of Internal Medicine (1980)

Letters and Corrections1 June 1980Thrombocytopenia and MinoxidilSTEVEN J. PEITZMAN, M.D., CLARENCE MARTIN, M.D.STEVEN J. PEITZMAN, M.D.Search for more papers by this author, CLARENCE MARTIN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-92-6-874_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Recently we cared for a patient who developed mild thrombocytopenia related in time to the ingestion of minoxidil (Loniten; Upjohn Company, Kalamazoo, Michigan), a potent oral vasodilator newly approved for the treatment of severe hypertension.A 49-year-old man came to the Veterans Administration Hospital on 1 December 1979 with weakness, anorexia, and dyspnea of 3 weeks' duration. For 20 years he had hypertension, which had been treated sporadically. His blood pressure was 240/140 mm Hg, and he was edematous. His serum creatinine was 12.7 mg/dL and urea nitrogen, 127 mg/dL. The hemoglobin content was 11 g/dL; leukocyte...Reference1. MIESCHER P. Drug-induced thrombocytopenia. Semin Hematol. 1973;10:311-25. MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Veterans Administration Medical Center Philadelphia, PA 19104 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byDrug ReactionsPruritic Rash with Actinic Keratosis and Impending Exfoliation in a Patient with Hypertension Managed with MinoxidilHypotensive drugs 1 June 1980Volume 92, Issue 6Page: 874-874KeywordsBlood pressureCreatinineDyspneaHemoglobinHypertensionIngestionUreaVasodilators Issue Published: 1 June 1980 PDF downloadLoading ...
Oesophageal motor changes in diabetes mellitus.
Authors: I M Stewart, D J Hosking, B J Preston, M Atkinson
Journal: Thorax (1976)

Radiography and manometry have been used to study oesophageal motor function in a group of 31 diabetics, 23 of whom had alimentary or genitourinary symptoms attributed to autonomic neuropathy. Peristalsis was of diminished amplitude and oesophageal emptying in the 15 degrees Trendelen-Peristalsis was of diminished amplitude and oesophageal emptying in the 15 degrees Trendelenburg position was delayed. The lower oesophageal sphincter pressure was reduced. The changes seldom caused symptoms and they were not confined to those diabetics with alimentary or genitourinary symptoms attributable to autonomic neuropathy. They suggest that autonomic neuropathy in diabetes is widespread and often subclinical. Degeneration of the ganglion cells of the oesophageal myenteric plexus is associated with hypersensitivity of the oesophageal smooth muscle to cholinergic agents. Bethanecol, a cholinergic drug with muscarinic actions, accelerated oesophageal emptying and increased the lower oesophageal sphincter pressure to normal levels in our diabetics but the hypersensitivity to this drug found in the presence of ganglion cell degeneration was not seen. This implies that in diabetic autonomic neuropathy the predominant lesion is in the preganglionic fibres of the vagus rather than in the myenteric plexus of the oesophageal wall.
Commentary: Validity of assessing change through audit
Authors: K. MacRae
Journal: BMJ (1994)

The difference between audit and research was neatly encapsulated by the subheading to a leading article by Smith: “Research is concerned with discovering the right thing to do; audit with ensureing that it is done right.”

Penney et al have reported an audit of the management of induced abortion in hospitals in Scotland, comparing the results obtained in a first round of six months in 1992 with those obtained in a second round of two months in 1993. 2The authors conclude that four statistically significant improvements were detectable when all 10 hospitals were taken together and that no overall deteriorations occurred in any elements of care. A rather different picture emerged when individual hospitals were considered. Considering 15 of the 16 criteria of care, giving 150 comparisons of the two rounds of audit, it was concluded that major improvements occured in 31 comparisons and significant deteriorations occurred in 11. Despite acknowledging that some of the improvements recorded …
Hypertension Control and Cardiovascular Outcomes Among Patients With Diabetes and Coronary Artery Disease
Authors: Kornelis J. J. van Hateren, Henk J. G. Bilo
Journal: JAMA (2010)

1. Werner RM, Bradlow ET. Relationship between Medicare’s Hospital Compare performance measures and mortality rates. JAMA. 2006;296(22):2694-2702. 2. Fonarow GC. Performance measures for patients hospitalized with heart failure: are they predictive of clinical outcomes? Congest Heart Fail. 2007;13(6): 342-346. 3. Nolan T, Berwick DM. All-or-none measurement raises the bar on performance. JAMA. 2006;295(10):1168-1170.
The Organization of Biologic Membranes
Authors: Philip Siekevitz
Journal: New England Journal of Medicine (1970)

WITH the partial working out of many of the pathways of intermediary metabolism, the mechanisms of enzyme action, of protein synthesis and of the genetic code, the springtime thoughts of biologists, molecular, chemical and cellular, have turned to what should be their first love: the organization of molecules into the functioning structures Abbreviations Used ER: endoplasmic reticulum NAD: nicotinamide adenine dinucleotide NADH: reduced nicotinamide adenine dinucleotide NADPH: neduced nicotinamide adenine dinucleotide phosphate of the cell. I do not allude to the isolation and morphologic and biochemical characterization of the organelles of the cell, such as nuclei, mitochondria and chloroplasts, but . . .
HOW IS THE EARLY DIAGNOSIS OF PULMONARY TUBERCULOSIS TO BE MADE?
Authors: R. G. McGowan
Journal: BMJ (1917)

C m lmJoU 741 for them free of charge under those Acts; h-lowever, such cases can be multiplied indefinitely wlhere people consider it more desirable to employ a handy-woman wlho remains in residence during the lying-in, period, and washes and liouselieeps for the household, wllile the unremunerated disiensary doctor is compelled to take over the work, and also the opprobritum of the untrained midwives' too- frequently-fatal mistakes.Where in the bill are we empowered to expel untrained women from the charge of a " Poor Law emnergency case " and substitute our trained lnurse?No suclh provision is made.Is the Local Government Board prepared to
883. AAV-2 Based Gene Therapy Using Novel Anti-VEGF Molecules for Inhibition of Angiogenesis in the Eye
Authors: Abraham Scaria, Peter Pechan, Hillard Rubin, Michael Lukason, Elizabeth Barry, Jeffrey Ardinger, Huawei Qiu, Qiuhong Li, James Peterson, William Hauswirth, Samuel Wadsworth
Journal: Molecular Therapy (2006)

Vascular endothelial growth factor (VEGF) plays a critical role in pathological neovascularization which is a key component of ocular diseases like wet age-related macular degeneration (AMD) or proliferative diabetic retinopathy (PDR). There are several reports of preclinical and clinical studies that demonstrate that antagonizing VEGF is a potentially useful strategy for treating such disorders. One of the most potent binders of VEGF is the VEGF receptor Flt-1. It has been shown in several publications that Flt-1 domains 2 and 3 are both required for efficient binding and neutralization of VEGF. In the current study we have engineered soluble hybrid forms of Flt-1 that represent novel high-affinity VEGF binders with binding affinities comparable to other known high affinity VEGF binders. The biological activity of these constructs was determined in vitro by the HUVECs proliferation assays, VEGF binding assays and BIAcore analysis. Since adeno-associated virus 2 (AAV2) mediated gene delivery offers a means to achieve local delivery of proteins into the eye we have inserted these novel anti-VEGF molecules into A AV2 vectors. In situ analysis and immunohistochemistry analysis of the mouse eye show that intravitreal administration of AAV2 based vector mediates transduction of retinal ganglion cells. Persistent transgene expression was observed for at least 13 months in the mouse eye following AAV2 mediated delivery and no gross transgene-related toxicities were observed. Two models for ocular angiogenesis were employed to access in vivo efficacy (1) The oxygen-induced retinopathy (OIR) model in mice as a model of retinal angiogenesis and (2) Laser induced choroidal neovasculaization model in mice. Data from both in vivo models suggests that these novel anti-VEGF molecules are potent inhibitors of retinal neovascularization.
ASPERMATOGENESIS, ANAPHYLAXIS, AND CUTANEOUS SENSITIZATION INDUCED IN THE GUINEA PIG BY HOMOLOGOUS TESTICULAR EXTRACT
Authors: Jules Freund, George E. Thompson, Murray M. Lipton
Journal: The Journal of Experimental Medicine (1955)

Guinea pig testicles were extracted with acetic acid; the extract was purified by removing material in consecutive precipitations with 30 per cent saturated ammonium-sulfate, trichloracetic acid, and chloroform. The solution so purified, when administered with complete adjuvants, was highly active in inducing impairment of spermatogenesis in guinea pigs. The activity resisted autoclaving at 15 pounds' pressure for 20 minutes, proteolytic enzymes, and formamide. Anaphylactic shock and cutaneous reaction to the purified homologous extract occurred in guinea pigs sensitized by the extract combined with adjuvants. For the production of aspermatogenesis it was essential to incorporate killed mycobacteria into the water-in-oil emulsion containing the antigen; but anaphylactic sensitization did not require the presence of mycobacteria.
Genetic Variations in the Glucocorticoid Receptor Gene Are Not Related to Glucocorticoid Resistance in Childhood Acute Lymphoblastic Leukemia
Authors: Wim J.E. Tissing, Jules P.P. Meijerink, Monique L. den Boer, Bas Brinkhof, Elisabeth F.C. van Rossum, Elisabeth R. van Wering, Jan W. Koper, Pieter Sonneveld, Rob Pieters
Journal: Clinical Cancer Research (2005)

Glucocorticoid sensitivity is an important prognostic factor in pediatric acute lymphoblastic leukemia (ALL). For its antileukemic effect, glucocorticoid binds the intracellular glucocorticoid receptor (GR) subsequently regulating transcription of downstream genes. We analyzed whether genetic variations within the GR gene are related to differences in the cellular response to glucocorticoids.In leukemic samples of 57 children, the GR gene was screened for nucleotide variations using a PCR/single-strand conformational polymorphism sequencing strategy. Data were linked to in vivo and in vitro glucocorticoid resistance.No somatic mutations were detected in the GR gene coding region, but six polymorphisms (i.e., ER22/23EK, N363S, BclI, intron mutation 16 bp upstream of exon 5, H588H, and N766N) were identified. In 67% of ALL cases, at least one minor allele of these polymorphisms was detected. Although only borderline significant, the incidence for the N363S polymorphism minor allele was higher (12% versus 6%, P = 0.06) and for the ER22/23EK minor allele lower (4% versus 7.6%, P = 0.1) than in a healthy, comparable population. The different genotypes of the polymorphisms were not related to prednisone resistance. In conclusion, polymorphisms but not somatic mutations in the GR gene coding region occur in leukemic blasts of children with ALL. Our data suggest that these genetic variations are not a major contributor for differences in cellular response to glucocorticoids in childhood ALL. The higher incidence of the N363S minor allele and the lower incidence of the ER22/23EK minor allele in our ALL population as compared with a normal population warrants further research.
Genomic architecture and evolution of clear cell renal cell carcinomas defined by multiregion sequencing
Authors: Marco Gerlinger, Stuart Horswell, James Larkin, Andrew J Rowan, Max P Salm, Ignacio Varela, Rosalie Fisher, Nicholas McGranahan, Nicholas Matthews, Claudio R Santos, Pierre Martinez, Benjamin Phillimore, Sharmin Begum, Adam Rabinowitz, Bradley Spencer-Dene, Sakshi Gulati, Paul A Bates, Gordon Stamp, Lisa Pickering, Martin Gore, David L Nicol, Steven Hazell, P Andrew Futreal, Aengus Stewart, Charles Swanton
Journal: Nature Genetics (2014)
Psychological implications of chemical and biological weapons
Authors: S. Wessely, K. C. Hyams, R. Bartholomew
Journal: BMJ (2001)

The ostensible purpose of chemical and biological weapons is to endanger lives. Biological agents, however, are particularly ineffective as military weapons, while chemical weapons have only limited uses. This may be why armies have generally acquiesced in international treaties to contain these unpredictable weapons and feel capable of waging war without them. Instead, chemical and biological weapons are quintessentially weapons of terror. The now routine journalistic association between chemical and biological weapons and the word terror confirms that the purpose of these weapons is to wreak destruction via psychological means—by inducing fear, confusion, and uncertainty in everyday life. 1 2 These effects will take two forms, acute and long term. It is customary to expect largescale panic if such weapons are ever effectively deployed or thought to be deployed.

We do not, however, know whether such panic would materialise. Media stories emerging from the United States …
Cardiac and metabolic effects of chronic growth hormone and insulin-like growth factor I excess in young adults with pituitary gigantism
Authors: Marta Bondanelli, Stefania Bonadonna, Maria Rosaria Ambrosio, Mauro Doga, Monica Gola, Alessandro Onofri, Maria Chiara Zatelli, Andrea Giustina, Ettore C. degli Uberti
Journal: Metabolism (2005)
A VISCERAL DEPRESSOR
Authors: David Hadden
Journal: JAMA (1913)

The illustration represents a device intended to take the place of the tablespoon or the trowel in the closure of the abdomen. The rubber web keeps the bowel from bulging to the side of the instrument and getting in the way, which occurs with the smooth metal depressor. Further, there is the greater advantage of being able to withdraw the instrument through a much smaller opening. Used in the pelvis, being opened after insertion, it serves as an excellent retractor to hold the bowel back from the pelvic organs without force or the irritation of gauze. There is weight enough to have it retain its position. For this purpose, however, I am having made an instrument with only one bend, and that at right angles. The rubber webs are replaceabie, withstand boiling, and are moderate in price.
Abstract 389: The functional relevance of decreased ANGPTL4 in human urinary bladder cancer.
Authors: Eduardo Cardenas, Tiffani Horton, Rita Ghosh
Journal: Cancer Research (2013)

Abstract Transitional cell carcinoma is the most common urothelial cancer in the US. Current therapeutic options have been unable to overcome issues with the highly recurrent nature of this tumor, which requires frequent follow-up making urinary bladder cancer, one of the most expensive solid tumors to manage. Microarray-based gene expression analysis in response to capsaicin treatment identified significant upregulation of angiopoietin-like 4 (ANGPTL4) compared with solvent-treated bladder cancer cells. The focus of this study was to determine the functional relevance of ANGPTL4 in normal urothelial and bladder cancer cells. The microarray data was validated in a panel of normal, immortalized and bladder cancer cells of increasing stage by real-time qPCR, immunoblotting, and ELISA. To determine the possible function of ANGPTL4, we knocked down and overexpressed ANGPTL4 in normal urothelial and bladder cancer cells respectively. The role of ANGPTL4 in growth, proliferation and angiogenesis was assessed. Our results show that normal urothelial cells have significantly higher levels of ANGPTL4 when compared to non-tumorigenic and bladder cancer cells. Upon capsaicin treatment ANGPTL4 levels increased in all cell lines tested. Overexpression of ANGPTL4 in the metastatic cell line TCCSUP, led to decrease in cell growth. Further, ANGPTL4 knockdown increased cell growth in the normal urothelial cell line. Capsaicin treatment decreased the expression of VEGF in bladder cancer cell lines UMUC-3 and T24 as well as reduced expression in normal urothelium, albeit initial results in ANGPLT4-knockdown in normal urothelium indicates no change in VEGF expression. Our results thus far suggest that the loss of ANGPTL4 expression may be involved in bladder cancer. The mechanism involved is under investigation. Capsaicin remains an attractive compound for further studies in bladder cancer. Supported by RO3 CA136058 (RG) and NIHT32 T32CA148724 (EC). Citation Format: Eduardo Cardenas, Tiffani Horton, Rita Ghosh. The functional relevance of decreased ANGPTL4 in human urinary bladder cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 389. doi:10.1158/1538-7445.AM2013-389
Attitudes of mothers to neonatal screening for Duchenne muscular dystrophy.
Authors: R A Smith, D K Williams, J R Sibert, P S Harper
Journal: BMJ (1990)

Early diagnosis of Duchenne musclar dystrophy is crucial if genetic counselling is to be offered to women at risk of carrying the relevant gene. The age at diagnosis is still unacceptably late,1 and we recently showed that screening programmes in infants are inadequate2; thus interest in neonatal screening has increased. Screening of infants has shown that assay of creatine kinase activity fulfils the criteria that should be satisfied by any technique used in neonatal screening programmes.3 Despite the lack of effective treat? ment neonatal screening programmes exist in some countries4 and the prevention of secondary cases has been put forward as a justifiable reason for introducing neonatal screening,5 although there are ethical prob? lems with this argument. We determined the attitudes of mothers towards neonatal screening for Duchenne muscular dystrophy.
Reversible Circumflex Coronary Artery Occlusion During Percutaneous Transvenous Mitral Annuloplasty With the Viacor System
Authors: Sandro Sponga, Olivier F. Bertrand, François Philippon, André St. Pierre, François Dagenais, Éric Charbonneau, Rodrigo Bagur, Mario Sénéchal
Journal: Journal of the American College of Cardiology (2012)