tbuckley/cabot-search huggingface dataset:
Biological bases for cancer dose-response extrapolation procedures.
Authors: J D Wilson
Journal: Environmental Health Perspectives (1991)

The Moolgavkar-Knudson theory of carcinogenesis of 1981 incorporates the viable portions of earlier multistage theories and provides the basis for both the linearized multistage and biologically based dose-response extrapolation methodologies. This theory begins with the premise that cancer occurs because irreversible genetic changes (mutations) are required for transformation of normal cells to cancer cells; incidence data are consistent with only two critical changes being required, but a small contribution from three or higher mutation pathways cannot be ruled out. Events or agents that increase the rate of cell division also increase the probability that one of these critical mutations will occur by reducing the time available for repair of DNA lesions before mitosis. The DNA lesions can occur from background causes or from treatment with mutagenic agents. Thus, the equations describing incidence as a function of exposure to carcinogenic agents include two separate terms, one accounting for mutagenic and one for mitogenic stimuli. At high exposures these interact, producing synergism and high incidence rates, but at low exposures they are effectively independent. The multistage models that are now used include only terms corresponding to the mutagenic stimuli and thus fail to adequately describe incidence at high dose rates. Biologically based models attempt to include mitogenic effects, as well; they are usually limited by data availability.
In situ leukemic plasmacytoid dendritic cells pattern of chemokine receptors expression and in vitro migratory response
Authors: N Bendriss-Vermare, L Chaperot, M Peoc'h, B Vanbervliet, M-C Jacob, F Briere, J-C Bensa, C Caux, J Plumas
Journal: Leukemia (2004)
Role of Transesophageal Echocardiography in the Diagnosis and Management of Traumatic Aortic Disruption
Authors: Philippe Vignon, Pascal Guéret, Jean-Marc Vedrinne, Philippe Lagrange, Elisabeth Cornu, Olivier Abrieu, Hervé Gastinne, Julien Bensaid, Roberto M. Lang
Journal: Circulation (1995)

Background Traumatic disruption of the aorta (TDA) is a life-threatening injury that requires rapid diagnosis and treatment. Emergency aortography, which is the current standard diagnostic imaging modality, is invasive, time-consuming, and difficult to perform in hemodynamically unstable patients with multiple trauma. We performed transesophageal echocardiography (TEE) in patients with suspected TDA to determine the diagnostic accuracy and impact on patient management of this alternative, portable imaging modality. Methods and Results Thirty-two consecutive trauma patients (mean age, 40±16 years) with suspected TDA (violent deceleration accident and mediastinum &gt;8 cm on admission chest x-ray) prospectively underwent a TEE examination in the emergency room. Findings during TEE were compared with those encountered during aortography, surgery, or necropsy. Two subsets of traumatic aortic injuries with distinct echocardiographic signs were observed: (1) subadventitial TDA (n=10) and (2) traumatic intimal tears (n=3). Eighteen patients had normal TEE confirmed by aortography. One 2-mm medial tear was missed by TEE (necropsy). The sensitivity and specificity of TEE for the diagnosis of subadventitial TDA were 91% and 100%, respectively. Patients with subadventitial TDA were taken to surgery immediately, whereas patients with intimal aortic tears were treated conservatively. Eighteen patients (mean age, 57±15 years) with confirmed acute aortic dissection involving the aortic isthmus were also included to establish the echocardiographic differential diagnostic criteria between this entity and TDA. Conclusions TEE should be considered the first-line imaging modality for the evaluation of trauma patients with suspected injuries of the thoracic aorta because of its portability, safety, diagnostic accuracy, and potential impact on patient management.
Correlation of Serum Alkaline Phosphatase of Intestinal Origin with the ABO Blood Group of Cirrhotics.
Authors: Leo L. Stolbach
Journal: Annals of Internal Medicine (1966)

s1 May 1966Correlation of Serum Alkaline Phosphatase of Intestinal Origin with the ABO Blood Group of Cirrhotics.Leo L. Stolbach, M.D., Melvin J. Krant, M.D., Susan C. Sebestyen, M.D., Norma I. Inglis, A.B., William H. Fishman, Ph.D.Leo L. Stolbach, M.D.Search for more papers by this author, Melvin J. Krant, M.D.Search for more papers by this author, Susan C. Sebestyen, M.D.Search for more papers by this author, Norma I. Inglis, A.B.Search for more papers by this author, William H. Fishman, Ph.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-64-5-1161_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptA number of isoenzymes of alkaline phosphatase have been found in human serum, and it has been assumed that liver and bone are the main tissue sources of these enzymes. A serum alkaline phosphatase of intestinal origin has now been identified by (1) its characteristic inhibition of enzyme activity in the presence of L-phenylalanine and (2) its location as a band of activity, after starch gel electrophoresis, migrating to the position for purified intestinal alkaline phosphatase. A similar band (unidentified as to organ source) has been related to the ABO blood types of normal individuals by other workers.The present... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Leo L. Stolbach, M.D.; Melvin J. Krant, M.D.; Susan C. Sebestyen, M.D.; Norma I. Inglis, A.B.; William H. Fishman, Ph.D.Affiliations: Boston, Massachusetts PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1966Volume 64, Issue 5Page: 1161-1162KeywordsBloodBlood groupsBoneEnzymesGel electrophoresisLiverPhenylalaninePhosphatasesStarches ePublished: 1 December 2008 Issue Published: 1 May 1966 PDF downloadLoading ...
Frank Alfred Schiess
Authors: Robert Neill
Journal: BMJ (2005)

the distinguished UK transplant immunologist and Nobel laureate.She spent her life supporting her husband's career and working hard for causes she cared about and believed in-the global environment, population control, and family planning.She was one of a redoubtable group of women who had to combat the most extraordinarily hostile attitudes in the early days of family planning.She was fond of quoting a letter published in the Lancet in 1930, when she was 17, saying that the subject "was something that no decent man would handle with a pair of tongs."In 1954, when she was 31, she met Margaret Pyke, chairwoman of the Family Planning Association, and this started her considerable contribution to the movement.She became a member of the executive in 1960, and was chairwoman from 1968 to 1970.For two decades, from 1957 to 1976, she was joint editor of Family Planning (now Family Planning Today).
A new apolipoprotein B truncation (apo B-43.7) in familial hypobetalipoproteinemia: Genetic and metabolic studies
Authors: Neelam Srivastava, Davide Noto, Maurizio Averna, Judit Pulai, Rai Ajit K. Srivastava, Thomas G. Cole, Mickey A. Latour, Bruce W. Patterson, Gustav Schonfeld
Journal: Metabolism (1996)
Knockout of insulin and IGF-1 receptors on vascular endothelial cells protects against retinal neovascularization
Authors: Tatsuya Kondo, David Vicent, Kiyoshi Suzuma, Masashi Yanagisawa, George L. King, Martin Holzenberger, C. Ronald Kahn
Journal: Journal of Clinical Investigation (2003)

Both insulin and IGF-1 have been implicated in control of retinal endothelial cell growth, neovascularization, and diabetic retinopathy. To precisely define the role of insulin and IGF-1 signaling in endothelium in these processes, we have used the oxygen-induced retinopathy model to study mice with a vascular endothelial cell–specific knockout of the insulin receptor (VENIRKO) or IGF-1 receptor (VENIFARKO). Following relative hypoxia, VENIRKO mice show a 57% decrease in retinal neovascularization as compared with controls. This is associated with a blunted rise in VEGF, eNOS, and endothelin-1. By contrast, VENIFARKO mice show only a 34% reduction in neovascularization and a very modest reduction in mediator generation. These data indicate that both insulin and IGF-1 signaling in endothelium play a role in retinal neovascularization through the expression of vascular mediators, with the effect of insulin being most important in this process.
Occurrence of Apoptosis, Secondary Necrosis, and Cytolysis in Eosinophilic Nasal Polyps
Authors: Lena Uller, Morgan Andersson, Lennart Greiff, Carl G. A. Persson, Jonas S. Erjefält
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

The paradigm states that inflammatory cells disappear from airway tissues through apoptosis and phagocytosis. However, cells may also be cleared through primary cytolysis, necrosis secondary to apoptosis, or transepithelial migration. This study examines the occurrence of apoptosis, secondary necrosis, and cytolysis of eosinophils in human nasal polyps in vivo and blood eosinophils in vitro. Eosinophils abounded in subepithelium and in paracellular epithelial pathways. Macrophages commonly occurred but without engulfed eosinophils. Scattered cells, including epithelial cells, were stained by antibody to the caspase cleavage product of poly(ADP-ribose) polymerase. Few cells were apoptotic (stained by terminal deoxy RNase nick end labeling). Of more than 3,000 examined tissue eosinophils, 110 were caspase cleavage positive, but only one was apoptotic. Transmission electron microscopy analysis of more than 500 eosinophils revealed viable and cytolytic eosinophils but not apoptosis, secondary necrosis, or engulfment of eosinophils. Plasma cells but neither epithelial cells nor eosinophils exhibited apoptotic ultrastructural morphology. Eosinophils in vitro exhibited different stages of apoptosis, ending with secondary necrosis distinct from in vivo eosinophil cytolysis. Our results show that the clearance of eosinophils from nasal polyps largely occurs through nonapoptosis pathways, including cytolysis and paraepithelial migration, and they challenge the belief that apoptosis is important for clearance of eosinophils from respiratory tissues.
Restructuring health systems for an era of prolonged austerity: an essay by Richard B Saltman and Zachary Cahn
Authors: R. B. Saltman, Z. Cahn
Journal: BMJ (2013)

<b>Richard B Saltman</b> and <b>Zachary Cahn</b> argue that efficiency savings are unlikely to enable health systems to cope with long term budget constraints and suggest that countries need to shift responsibility for substantial parts of health activity away from the public sector
A Concise Review of Pulmonary Sarcoidosis
Authors: Robert P. Baughman, Daniel A. Culver, Marc A. Judson
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Section:ChooseTop of pageAbstract <<ETIOLOGY AND PATHOGENESISDIAGNOSISTHERAPYCONCLUSIONSReferencesCITING ARTICLES
Ets-1 mediates platelet-derived growth factor-BB-induced thrombomodulin expression in human vascular smooth muscle cells
Authors: I.-Chung Lo, Tsun-Mei Lin, Ling-Hui Chou, Shu-Lin Liu, Li-Wha Wu, Guey-Yueh Shi, Hua-Lin Wu, Meei Jyh Jiang
Journal: Cardiovascular Research (2008)

Thrombomodulin (TM), a potent anticoagulant, is not detected in quiescent vascular smooth muscle cells (VSMCs). In diseased vessels, VSMC expresses TM, but the mechanisms are unclear. This study examined molecular mechanisms for TM expression in VSMCs.Platelet-derived growth factor-BB (PDGF-BB) induced TM expression in cultured human aortic VSMCs. PDGF-induced TM is functional in activating protein C. TM induction was eliminated by inhibitors of Src kinase, phosphatidylinositol 3-kinase (PI3-kinase), and mammalian target of rapamycin (mTOR) and by expressing dominant-negative Akt while expressing active Akt-stimulated TM expression. PDGF-BB activated the TM promoter, and the deletion of a sequence segment -394/-255 drastically reduced TM promoter activity. Transcription factor E26 transformation-specific sequence-1 (Ets-1) was upregulated by PDGF-BB in a PI3-kinase- and mTOR-dependent manner. RNA interference of Ets-1 inhibited PDGF induction of TM, and overexpressing Ets-1 increased TM expression. Chromatin immunoprecipitation and electrophoretic mobility shift assay detected increased Ets-1 binding to the TM promoter after PDGF treatment. Following carotid artery ligation of C57/BL6 mice, PDGF-BB and TM were co-expressed in the media and neointima.In VSMCs, PDGF-BB stimulates TM expression that is mainly mediated by Ets-1 via the Src kinase/PI3-kinase/Akt/mTOR signalling pathway. Furthermore, PDGF-BB may regulate TM expression in VSMCs during vascular remodelling.
Oral contraception and health
Authors: D. C G Skegg
Journal: BMJ (1999)

General practice p 96

Oral contraceptives have been studied more intensively than any other medication in history. Yet the recent brouhaha about third generation oral contraceptives and venous thromboembolism is only the latest in a series of “pill scares” over more than three decades. For some mysterious reason these periodic crises have been a particular feature of Britain; during the 1980s, for example, false alarms about major effects on breast cancer risk created greater consternation in Britain than elsewhere. While the British media have often produced more heat than light, scientists in Britain have contributed more than their share of evidence about the safety of oral contraceptives. One project that has become a landmark of epidemiology is the Royal College of General Practitioners' oral contraception study, and this week sees another publication from the study (p 96).1

In 1968Dr Clifford Kay and his colleagues persuaded 1400general practitioners to enrol 46000 women (half of whom were using oral contraceptives at the time) into a follow up study. Meticulous observations over many years have produced important information about many health outcomes. 23 In …
Effects of gold salts and prednisolone on inflammatory cells. I. Phagocytic activity of macrophages and polymorphs in inflammatory exudates studied by a "skin-window" technique in rheumatoid and control patients.
Authors: J D Jessop, B Vernon-Roberts, J Harris
Journal: Annals of the Rheumatic Diseases (1973)

Whatever the stimulus to inflammation, for example traumatic, bacterial or immunological damage to tissues, macrophages and neutrophil polymorphs usually accumulate in large numbers in the inflamed area, and there is abundant experimental evidence that these cells originate in the bone marrow (Volkman and Gowans, 1965a, b; Spector and Willoughby, 1968).Inflammation of synovial tissues is a cardinal feature of rheumatoid arthritis and vari- able numbers of macrophages and polymorphs are present within the synovium and synovial fluid in affected joints.Lysosomal enzymes of the macro- phages and polymorphs present in rheumatoid pan- nus are actively concerned in the destruction of articular cartilage (Dingle, 1969; Chayen and Bitensky, 1971).In addition to their phagocytic and on July 10,
Identification of persons with cardiorespiratory conditions who are at risk of dying from the acute effects of ambient air particles.
Authors: M S Goldberg, R T Burnett, J C Bailar, R Tamblyn, P Ernst, K Flegel, J Brook, Y Bonvalot, R Singh, M F Valois, R Vincent
Journal: Environmental Health Perspectives (2001)

This study was undertaken to identify subgroups of the population susceptible to the effects of ambient air particles. Fixed-site air pollution monitors in Montreal, Quebec, Canada, provided daily mean levels of various measures of particulates and gaseous pollutants. Total sulfates were also measured daily (1986-1993) at a monitoring station 150 km southeast of the city (Sutton, Quebec, Canada). We used coefficient of haze (COH), extinction coefficient, and Sutton sulfates to predict fine particles and sulfates from a fine particles model for days that were missing. We used the universal Quebec medicare system to obtain billings and prescriptions for each Montreal resident who died in the city from 1984 to 1993. These data were then used to define cardiovascular and respiratory conditions that subjects had before death. Using standard Poisson regression time-series analyses, we estimated the association between daily nonaccidental mortality and daily concentrations of particles in the ambient air among persons with cardiovascular and respiratory conditions diagnosed before death. We found no persuasive evidence that daily mortality increased when ambient air particles were elevated for subgroups of persons with chronic upper respiratory diseases, airways disease, cerebrovascular diseases, acute coronary artery disease, and hypertension. However, we found that daily mortality increased linearly as concentrations of particles increased for persons who had acute lower respiratory diseases, chronic coronary artery diseases (especially in the elderly), and congestive heart failure. For this latter set of conditions, the mean percent increase in daily mortality (MPC) for an increase in the COH across its interquartile range (18.5 COH units per 327.8 linear meters), averaged over the day of death and the 2 preceding days, was MPC = 5.09% [95% confidence interval (CI) 2.47-7.79%], MPC = 2.62 (95% CI 0.53-4.75%), and MPC = 4.99 (95% CI 2.44-7.60%), respectively. Adjustments for gaseous pollutants generally attenuated these associations, although the general pattern of increased daily mortality remained. In addition, there appeared to be a stronger association in the summer season. The positive associations found for persons who had acute lower respiratory diseases and congestive heart failure are consistent with some prevailing hypotheses and may also be consistent with recent toxicologic data implicating endothelins. Further epidemiologic studies are required to confirm these findings.
Instantaneous pressure-volume relationship of the canine right ventricle.
Authors: W L Maughan, A A Shoukas, K Sagawa, M L Weisfeldt
Journal: Circulation Research (1979)

The instantaneous isovolumic and ejecting pressure-volume relationship of the right ventricle was studied in 11 cross-circulated, isolated canine hearts to characterize the right ventricular contractile state.Accurate measurement of volume was achieved by the use of a water-filled, thin latex balloon in the right ventricle connected to a special volume loading and transducing chamber.Pressure was measured with a miniature pressure transducer mounted within the balloon.Wide variations in loading conditions were achieved by changing the volume of air above the volumetric chamber.The pressure and volume data were collected from multiple beats under a constant contractile state in the same mode of contraction while the left ventricle was vented to air.Linear regression analysis applied to each of the isochronal pressure-volume data sets at 20-msec intervals from the onset of contraction showed a highly linear correlation between the pressure and the volume.Both the slope and the volume intercept of the regression lines changed with time throughout the cardiac cycle.The maximal slope of the regression line (E,,,,) averaged 2.50 ± 0.49 mm Hg/ml (mean ± SD) for ejecting beats and 2.68 ± 0.55 mm Hg/ml for isovolumic beats.Epinephrine infusions of 12.5 fig/min and 25.0 /ig/min increased E^u by 31% and 82%, respectively (P < 0.005).We conclude that: (1) The instantaneous pressure-volume relationships of the right ventricle in the isovolumic and ejecting modes can be regarded as linear, at least within the physiological range; however, these two modes of contraction did not yield an identical relationship.(2) The slope of these pressure-volume relationship curves changes with a change in the contractile state.
Liver cell adenoma at the age of 3 years and transplantation 19 years later after development of carcinoma: A case report
Authors: Christine H. Janes, Douglas B. McGill, Jurgen Ludwig, Ruud A. F. Krom
Journal: Hepatology (1993)

A 3-yr-old child underwent biopsy of a nonresectable liver cell adenoma. She was well thereafter, but at the age of 22 yr, she underwent orthotopic liver transplantation because the lesion had grown. The α-fetoprotein level was 4,300. The specimen showed poorly differentiated hepatocellular carcinoma in a noncirrhotic liver. At this writing, the patient is well 32 mo after transplantation. (Hepatology 1993;17:583-585.)
The effect of short-term prophylactic methylprednisolone on the incidence and severity of postpericardiotomy syndrome in children undergoing cardiac surgery with cardiopulmonary bypass
Authors: Antonio R Mott, Charles D Fraser, Anita V Kusnoor, N.Martin Giesecke, George J Reul, Kathy L Drescher, Carmen H Watrin, E.O’Brian Smith, Timothy F Feltes
Journal: Journal of the American College of Cardiology (2001)
ACUTE PANCREATITIS: A METHOD OF TREATMENT
Authors: R. G. Henderson
Journal: BMJ (1927)

THx B 1095 varies within considerable limits as to the diagnosis of nystagmus; County Court judges are also much perturbed in such cases.All these facts indicate that some authorita- tive definition of the disease and its many phases is urgently required.W Whatever opinion is held as to the causation of nystagmus the pathological entity round which this complex revolves is involuntary oscillation of eyeballs, and that, in my opinion, cannot be explained away on a psychological basis.To the elucidation of the cause of this defect in the miner the expert coal chemist should add his quota to that of the doctor.
Reorganization of National Health Service 1974 —for Better or for Worse?
Authors: John Lister
Journal: New England Journal of Medicine (1973)

LATER this year National Health Service will celebrate its silver jubilee, and next year it is due to undergo a complete reorganization. Ever since the Service began there have been problems arising from its tripartite structure. Thus, the work of general practitioners has been organized by a network of executive councils, the work in district hospitals has been organized by regional hospital boards, and that in teaching hospitals by boards of governors, with local authorities retaining responsibility for the community health services. For many years it has been suggested by many different people that an integrated service with one authority . . .
Choosing a doctor in the USSR.
Authors: J T Hart
Journal: BMJ (1979)

fetal serum AFP that enters the amniotic fluid in the presence of a normal conceptus.Our results and those of Ruoslahti and colleagues emphasise that the AFP con A- binding assay on amniotic fluid has particular value in detecting the presence of communi- cating fetal abnormalities during the period when amniocenteses are usually performed, between the 14th and 18th weeks, in cases where the elevations of amniotic fluid AFP are equivocal or when gestational aging is uncertain.
Genetic Testing of Families With Hereditary Diseases-Reply
Authors: Caryn Lerman
Journal: JAMA (1996)

In Reply.  —We thank Dr Olopade and Dr Thurmon for sharing their data on use of genetic counseling. Consistent with other studies,1,2these reports suggest that rates of utilization of genetics services may vary substantially depending on such factors as mode of enrollment and financial costs. We agree strongly with Olopade's comments about the need to improve access to genetic testing research protocols, and we hope that this will be achieved by the Cancer Genetics Network, a national cooperative study on cancer genetics and testing proposed by the National Institutes of Health.3  We also appreciate the clarification by Dr Wexler regarding the conclusions of a previous study of predictive testing for theHDgene.4Wexler also highlights the important fact that some individuals who receivedHDgene test results did experience adverse psychological effects. As we have pointed out, examination of average responses in study groups may obscure important