tbuckley/cabot-search huggingface dataset:
S111 The role of TNF-related apoptosis inducing ligand (TRAIL) in pulmonary fibrosis
Authors: E. E. McGrath, A. Lawrie, H. Marriott, P. F. Mercer, S. S. Cross, R. C. Chambers, D. H. Dockrell, M. K. B. Whyte
Journal: Thorax (2011)

<h3>Introduction</h3> The concept of driving cellular apoptosis as a potential therapy for diseases characterised by inappropriate cellular persistence or proliferation is of widespread interest. We previously showed a death receptor ligand, TRAIL, accelerates neutrophil apoptosis without associated cell activation (<i>J Immunol</i><b>170</b>:1027–33) and other work revealed TRAIL-induced apoptosis of human lung fibroblasts. The aims of this project were to study the role of TRAIL in a bleomycin lung injury model in wild-type and TRAIL−/− mice and in patients with idiopathic pulmonary fibrosis (IPF). <h3>Methods</h3> Mice received intratracheal bleomycin or saline control. Bronchoalveolar lavage (BAL) at 3, 7, 16 and 23 days was analysed by cytospin morphology and haemocytometer count for % neutrophils, % neutrophil apoptosis, total number of neutrophils and total number of apoptotic cells. Flow cytometry was also used to analyse apoptosis. Collagen deposition in whole lung samples was analysed using a hydroxyproline assay. TRAIL expression and TUNEL positive events were also analysed. Serum and lung tissue from IPF patients/controls were examined for TRAIL expression and concentration. Lung function and survival data were retrieved from patient charts. <h3>Results</h3> BAL analysis revealed statistically significant differences between TRAIL−/− and wild-type mice, with TRAIL−/− mice showing increased neutrophil numbers and reduced neutrophil apoptosis as absolute count or as % total cell count. Collagen deposition was statistically greater in TRAIL−/− mice at 16 days. At day 23, TRAIL−/− mice had decreased TUNEL positive events compared to wild-type mice. Histological analysis of murine lung sections revealed specific TRAIL expression in bronchus associated lymphoid tissue and alveolar macrophages. IPF patient lung section analysis revealed an absence of TRAIL expression compared to controls. IPF patients had significantly lower serum levels of TRAIL than controls which inversely correlated with TLCO (% predicted) and positively correlated with survival from diagnosis. <h3>Conclusions</h3> We demonstrated that the neutrophilic inflammatory response to bleomycin is increased in TRAIL−/− compared with wild-type mice and that this finding is associated with increased collagen deposition. We also demonstrated reduced pulmonary and systemic expression of TRAIL in IPF, which correlates with worse pulmonary function and clinical outcome. This data suggests TRAIL may have biomarker potential and therapeutic benefit in pulmonary fibrosis.
ASSOCIATION OF MYOCARDIAL EXTRACELLULAR VOLUME AND CLINICAL OUTCOME: A CARDIAC MAGNETIC RESONANCE STUDY
Authors: Mohamad Ghassan Ghosn, Stephen Pickett, Gerd Brunner, Faisal Nabi, William Zoghbi, Miguel Quinones, Vijay Nambi, Dipan Shah
Journal: Journal of the American College of Cardiology (2015)
Syphilis and Social Upheaval in China
Authors: Joseph D. Tucker, Xiang-Sheng Chen, Rosanna W. Peeling
Journal: New England Journal of Medicine (2010)

Syphilis was nearly eliminated from China 50 years ago but is now the most commonly reported communicable disease in Shanghai. Dr. Joseph Tucker and colleagues write that the Chinese syphilis epidemic holds important lessons about social and environmental influences on sexual health.
Infected Breast Reconstruction Associated with Poland??s Syndrome
Authors: CHARLES A. STEWART, GUO-LONG HUNG, ANNE M. GLASER, HARVEY N. HIMEL
Journal: Clinical Nuclear Medicine (1990)

A 21-year-old woman with left breast hypoplasia associated with Poland's syndrome underwent breast reconstruction: removal of a previous implant, capsulotomy, and transverse myocutaneous island flap to the left chest. Eight weeks later, she returned with purulent drainage and cellulitis. Chest radiographs and radionuclide bone imaging demonstrated rib deformities of Poland's syndrome but no evidence of osteomyelitis. The bone scan also revealed abnormal soft tissue accumulation in the area of the reconstruction. Computerized tomography showed nonhomogeneous soft tissue density of the reconstruction compatible with fat and fibrous tissue. A gallium scan confirmed infection of the reconstruction. Debridement revealed extensive fat necrosis with cultures positive for Staphylococcus epidermidis and Streptococcus viridans. There was an excellent response to antibiotic therapy after debridement.
Treating Mild Hypertension
Authors: Nemat O. Borhani, Herbert G. Langford
Journal: Annals of Internal Medicine (1984)

Letters and Corrections1 February 1984Treating Mild HypertensionNEMAT O. BORHANI, M.D., HERBERT G. LANGFORD, M.D.NEMAT O. BORHANI, M.D.Search for more papers by this author, HERBERT G. LANGFORD, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-100-2-312_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The editorial by Ram (1) on the treatment of mild hypertension compiled into one article a number of arguments offered by others about the Hypertension Detection and Follow-up Program and the other trials on the treatment of mild hypertension. Because the points made by Dr. Ram are erroneous, some factually and some in their interpretation, we believe they should be clarified.First let us consider the claim that a "small percentage" of participants in the Hypertension Detection and Follow-up Program benefited. It is certainly true that when one subtracts mortality rate among the referred care group from...References1. RAM C. Should mild hypertension be treated [Editorial]? Ann Intern Med. 1983;99:403-5. LinkGoogle Scholar2. HARDY R and HAWKINS C. The impact of selected indices of antihypertensive treatment on all-cause mortality. Am Epidemiol. 1983;117:566-74. CrossrefMedlineGoogle Scholar3. . The effect of treatment on mortality in "Mild" hypertension: results of the Hypertension Detection and Follow-up Program. N Engl J Med. 1982;307:976-80. Google Scholar1. Five-year findings of the Hypertension Detection and Follow-up Program. I. Reduction in mortality of persons with high blood pressure, including mild hypertension. JAMA. 1979;242:2562-71. CrossrefMedlineGoogle Scholar2. PICKERING T. Treatment of mild hypertension and the reduction of cardiovascular mortality: the "of or by" dilemma. JAMA. 1983;249:399-400. CrossrefMedlineGoogle Scholar3. . Untreated mild hypertension. Lancet. 1982;1:185-91. MedlineGoogle Scholar4. MANAGEMENT COMMITTEE OF THE AUSTRALIAN HYPERTENSION TRIAL. Initial results of the Australian Therapeutic Trial in Mild Hypertension. Clin Sci. 1979;57:449S-52S. CrossrefMedlineGoogle Scholar5. . Multiple risk factor intervention trial: risk factor changes and mortality results. JAMA. 1982,248:1465-77. CrossrefMedlineGoogle Scholar6. BULPITT C. Prognosis of treated hypertension 1951-1981. Br J Clin Pharmacol. 1982;13:73-9. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: NEMAT O. BORHANI, M.D.; HERBERT G. LANGFORD, M.D. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byMild hypertension: A therapeutic dilemma 1 February 1984Volume 100, Issue 2Page: 312-313KeywordsDeath ratesHypertension ePublished: 1 December 2008 Issue Published: 1 February 1984 PDF downloadLoading ...
Non-attendance or non-invitation?
Authors: I. A. Davidson
Journal: BMJ (1989)

Some patients were given volume loading to improve cardiac output after the application of positive end expiratory pressure.Without measurements of wedge pressure the volume of fluid required is difficult to assess, and clinical indicators of volume state in this type of patient are not accurate.In addition, to maintain optimal oxygen delivery and cardiac output in the face of a high positive end expiratory pressure it mav be necessary to utilise vasoactive drugs.These drugs have unpredictable and sometimes deleterious effects on oxygen transport and respiratory func- tion (particularly pulmonary venous admixture).Unless mixed venous oxygen saturation and oxygen consumption are monitored these effects, which may make tissue hypoxia worse, will be missed.We agree that the study of Drs Singer and Bennett confirms the need for haemodynamic monitoring.Measurements should also be made to ensure that optimal global oxygen transport has been achieved, which, with our present under- standing and technical skill, will necessitate pulmonary artery catheterisation.
A TYPE OF CHRONIC PERITONITIS APPARENTLY DUE TO INTESTINAL INFECTION
Authors: ANTHONY BASSLER
Journal: JAMA (1941)

The peritoneum itself is very resistant to infection. In this it probably represents a bactericidal ability beyond any other tissue in the body. This bactericidal ability is especially marked with intestinal organisms, such as those of the coliform group. That the peritoneum is constantly assailed by bacteria is suggested by the work of Roberts, Johnson and Bruckner, 1 in which it was shown that in 80 per cent of the instances, and irrespective of intraperitoneal inflammatory reaction, positive cultures were obtained. These differed from the bacteriology of the air and were of intestinal micro-organisms. In noninflammatory conditions a staphylococcus was recovered in 11.2 per cent. Ordinarily these organisms are cared for by the peritoneum, the lymph and vascular systems and the blood. While the ability of the peritoneum to destroy organisms is high, it apparently is not complete in that in 6 per cent of healthy persons on one vein
Computerised evidence based guidelines in primary care: Authors' reply
Authors: M. Eccles
Journal: BMJ (2003)

EDITOR—The enduring message from researching methods to promote the uptake of research findings is that no one strategy that will work for all individuals, settings and behaviours,1 yet this is what both Prince and Lipman imply.

It is understandable that Prince promotes a locally developed computerised decision support system addressing local needs and priorities, particularly as …
Freud and Kronos
Authors: JEROME M. SCHNECK
Journal: American Journal of Psychiatry (1968)

In one of Freud's uncompleted works, published posthumously, reference is made to Kronos eating his children and being castrated by his son, Zeus, in retaliation. However, inspection of extant versions of the myth shows Zeus banishing but not castrating his father, whereas Kronos had previously castrated his own father, Uranus. The reasons for Freud's error are a point of speculation.
Abstract 1368: Fragment-based design, synthesis and biological evaluation of a series of novel PDK1 inhibitors
Authors: Sunil Sharma, Sorna Venkataswamy, Steven L. Warner, Lee T. Call, David J. Bearss, Hariprasad Vankayalapati
Journal: Cancer Research (2011)

Abstract The PDK1 is a monomeric serine/threonine kinase and a promising oncology target of significant current interest for drug development due to its central role in the PI3K/AKT/mTOR pathway. It phosphorylates highly conserved Ser or Thr residues in the activation loop of several AGC super family kinases including PKC, SGK, PKB/Akt, p70S6K, and PDK-1 itself. Approximately, 40-50% of all tumors involve mutations in the PTEN protein, which results in elevated levels of PIP3 and enhanced activation of PKB/AKT, p70S6K, and SGK. It has been proposed that inhibitors of PDK-1 could provide a valuable therapeutic approach to targeting cancer, particularly those with PTEN deficiencies. Using a fragment-based design strategy, we screened a collection of 1100 low molecular weight (&amp;lt; 250 MW) fragments against the PDK1 kinase and identified 9 fragments with moderate inhibitory activity against PDK1 (IC50 values from 45-82 μM). Of these fragments, those based off of a 5-Br,4-I-1H-indazol-3-amine scaffold seemed the most promising based on initial activity and in keeping with the “rule of 3” for fragment-based drug design. Subsequent molecular docking studies using a crystal structure of PDK1 allowed for the structural rationalization of how these fragments bound in the ATP-binding pocket (hydrogen bonding to S160/A162 hinge residues) and provided insight for further optimization. Concurrently, we carried out scaffold-hopping searches at 2-site points for hydrophobic and solvent pocket fragments. With the addition of one fused heterocyclic ring, the potency increased to 8.8 and 10.9 μM. Our systematic fragment based workflow led to the preparation of target molecules in 4 steps beginning with the condensation, cyclization, and reduction and finally installing the hydrophobic binding site fragments under normal amide coupling. Subsequent SAR and follow-up screening led to the discovery of HCI-1680, a potent PDK1 inhibitor with an IC50 of 97 nM. Additional productive interactions sites with PDK1 were introduced to further improve both biochemical and cellular activities in panel of cancer cells. In cell-based assays HCI-1680 demonstrated enhanced activity in PTEN-deficient cell lines compared to PTEN-wild type lines. HCI-1680 and additional compounds from this series were also shown to inhibit the activation of AKT and other downstream signaling molecules. Kinase selectivity profiling, additional cell-based assays, and animal studies are ongoing. The details of these studies will be presented. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1368. doi:10.1158/1538-7445.AM2011-1368
The doctor and the child with learning problems
Authors: A. Bolton
Journal: BMJ (1984)

<h3>Objectives</h3> The objective of this study was to compare the prevalence of polydrug use, use of drugs associated with chemsex, specific drug use, and HIV-related behaviours, between two time periods, using two groups of HIV-negative men who have sex with men (MSM) attending the same sexual health clinics in London and Brighton, in two consecutive periods of time from 2013 to 2016. <h3>Methods</h3> Data from MSM in the cross-sectional Attitudes to and Understanding Risk of Acquisition of HIV (AURAH) study (June 2013 to September 2014) were compared with baseline data from different MSM in the prospective cohort study Attitudes to and Understanding Risk of Acquisition of HIV over Time (AURAH2) (November 2014 to April 2016). Prevalence of polydrug use, drug use associated with chemsex and specific drug use, and 10 measures of HIV-related behaviours including condomless sex, post-exposure prophylaxis (PEP) use, pre-exposure prophylaxis (PrEP) use, and HIV testing, were compared. Prevalence ratios (PRs) for the association of the study (time period) with drug use and HIV-related behaviour measures were estimated using modified Poisson regression analysis, unadjusted and adjusted for sociodemographic factors. <h3>Results</h3> In total, 991 MSM were included from AURAH and 1031 MSM from AURAH2. After adjustment for sociodemographic factors, use of drugs associated with chemsex had increased (adjusted PR (aPR) 1.30, 95% CI 1.11 to 1.53) and there were prominent increases in specific drug use; in particular, mephedrone (aPR 1.32, 95% CI 1.10 to 1.57), γ-hydroxybutyric/γ-butryolactone (aPR 1.47, 95% CI 1.15 to 1.87) and methamphetamine (aPR 1.42, 95% CI 1.01 to 2.01). Use of ketamine had decreased (aPR 0.54, 95% CI 0.38 to 0.78). Certain measures of HIV-related behaviours had also increased, most notably PEP use (aPR 1.50, 95% CI 1.21 to 1.88) and number of self-reported bacterial STI diagnoses (aPR 1.24, 95% CI 1.08 to 1.43). <h3>Conclusions</h3> There have been significant increases in drug use associated with chemsex and some measures of HIV-related behaviours among HIV-negative MSM in the last few years. Changing patterns of drug use and associated behaviours should be monitored to enable sexual health services to plan for the increasingly complex needs of some clients.
Engineering Oncolytic Measles Virus to Circumvent the Intracellular Innate Immune Response
Authors: Iana Haralambieva, Ianko Iankov, Kosei Hasegawa, Mary Harvey, Stephen J Russell, Kah-Whye Peng
Journal: Molecular Therapy (2007)

The innate antiviral responses of tumor cells are often impaired but may still be sufficient to impede the intratumoral spread of an oncolytic virus. Here, we establish that the oncolytic measles virus (MV-eGFP) induces interferon (IFN) production in human myeloma and ovarian cancer cells. In addition, MV gene expression and virus progeny production were inhibited by IFN treatment of these tumor cells. The P gene of wild-type measles virus encodes P/V/C proteins known to antagonize IFN induction and/or response. We therefore engineered MV-eGFP for IFN evasion and more efficient intratumoral spread by arming it with the P gene from wild-type IC-B strain MV, thus generating MV-eGFP-Pwt. The chimeric virus exhibited reduced IFN sensitivity and diminished capacity to induce IFN in BJAB lymphoma, ARH-77 myeloma cells, and activated peripheral blood mononuclear cells. Interestingly, unlike the wild-type MV, MV-eGFP-Pwt was unable to shut down IFN induction completely. In immunocompromised mice bearing human myeloma xenografts, intravenously administered MV-eGFP-Pwt showed significantly enhanced oncolytic potency compared to MV-eGFP. These results indicate that oncolytic viruses are subject to control by the innate immune defenses of human tumor cells and may therefore be more effective if their natural ability to combat innate immunity is maintained.
Type D (Delta) Hepatitis
Authors: Jay H. Hoofnagle
Journal: JAMA (1989)

<h3>SELECTED CASE</h3> A 40-YEAR-OLD New York man presented with complaints of fatigue. Five years previously he had an episode of acute hepatitis B from which he recovered symptomatically. In followup, however, he had persistently elevated serum alanine aminotransferase levels and hepatitis B surface antigen (HBsAg). A year previously he had a recurrence of symptoms of hepatitis with jaundice, anorexia, and malaise, after which he had persistent fatigue and intermittent abdominal discomfort. His medical history was unremarkable. He was born in Germany of Italian heritage. He was a sexually active, male homosexual but denied drug abuse, alcoholism, blood transfusions, and medications. Physical examination revealed mild hepatosplenomegaly, lymphadenopathy, and spider angiomata over the upper part of the chest. Laboratory test results included serum bilirubin level, 17 μmol/L; alanine aminotransferase level, 269 U/L (normal, &lt;45 U/L); alkaline phosphatase level, 77 IU/L (normal, &lt;115 IU/L); albumin level, 33 g/L (normal, 38 to 50 g/L);
BLENNORRHCEA.Abstract of Paper read before the Mississippi Valley Medical Assomdation.
Authors: JAMES J. T. JELKS
Journal: JAMA (1891)

suits of the rheumatic inflammation was due to the collateral treatment, static faradization and exhibition of the iodides, as well as the strong mental stimulus of knowing that on July 18, 1891, he must return to duty or lose his place.Such is the record of experiences and observa¬ tion which we lay before the reader, and upon which we base our plea for "known and definite quality and quantity in mineral waters."The record is the reason for the faith that is in us.The results attained are our justification in de¬ claring for the honest, scientific, known artificial product, in preference to the dishonest, unscien¬ tific, unknown and unreliable so-called natural product.The rule, in the use of the latter, is disappointment and failure ; in the use of the former, definite, successful results, giving profit and pleasure.BLENNORRHCEA.
Solving the Staffing Problem
Authors: E. N. Owen
Journal: BMJ (1970)

stuck.We have become, I am afraid, the Cinderella grade of the profession and a mi- nority group the B.M.A. can well afford to neglect.Support for this view is found in the Twelfth Review Body Report, paragraph 99, which states that the Associa- tion claimed that there should be a differential between the top of the scale of medical assistants and the bottom of the scale of consultants.Fortunately, the Review Body, in its wisdom, rejected this.
Molecular regulatory mechanism of tooth root development
Authors: Xiao-Feng Huang, Yang Chai
Journal: International Journal of Oral Science (2012)

The root is crucial for the physiological function of the tooth, and a healthy root allows an artificial crown to function as required clinically. Tooth crown development has been studied intensively during the last few decades, but root development remains not well understood. Here we review the root development processes, including cell fate determination, induction of odontoblast and cementoblast differentiation, interaction of root epithelium and mesenchyme, and other molecular mechanisms. This review summarizes our current understanding of the signaling cascades and mechanisms involved in root development. It also sets the stage for de novo tooth regeneration.
Crohn's Disease Involving Stomach
Authors: F. R. R. Martin, R. J. Carr
Journal: BMJ (1953)

A" Group Hospitals - Crohn's disease is now a well-recognized pathological and clinical entity.It is generally agreed that the characteristic lesions occur predominantly in the terminal ileum, but that " skip " lesions are found anywhere in the jejunum, ileum, or colon.Crohn (1949) describes three maln varieties: regional ileitis, ileo-jejunitis, and ileo-colitis.He' also mentions cases in which the second and third parts of the duodenum were involved, and states that in two of these there were radiological appearances suggesting spread of the disease to the stomach.So far as we are aware, no cases have been published in which there has been proof of the disease occurring in the stomach, nor have the clinical or radiological features been described.In the following two cases Crohn's disease was shown to be present in the stomach.Case 1
Pigment epithelium derived factor--the product of the EPC-1 gene--is expressed by articular chondrocytes and up regulated in osteoarthritis
Authors: D Pfander
Journal: Annals of the Rheumatic Diseases (2005)

Proper function of a loadbearing joint depends on the structural integrity of articular cartilage, which can absorb and respond to mechanical stress.1 Increased synthesis of VEGF-A is assumed to be involved in cartilage neovascularisation in osteoarthritis (OA), thus contributing to cartilage damage during the course of OA.2,3

Previously, we and others have provided experimental evidence that VEGF-A synthesis by OA chondrocytes is controlled by the transcription factor hypoxia-inducible factor-1α.2–4 In contrast, pigment epithelium derived factor (PEDF) is one of the most potent natural inhibitors of angiogenesis and was recently described as being present in growth plate cartilage.5 PEDF constitutes a 50 kDa protein and is encoded by the EPC-1 gene.6,7 Based on our previous work, we aimed to determine whether PEDF is expressed in human normal and OA knee cartilage.

Twenty nine cartilage samples were obtained from patients during total knee replacement. In addition, nine human normal cartilage samples were obtained during necropsies. After fixation, specimens were embedded in paraffin wax, stained with safranin O, and were graded according to Mankin et al .8 For immunodetection of PEDF two different antibodies were used (polyclonal 1:100, Santa-Cruz Biotechnology Inc, …