tbuckley/cabot-search huggingface dataset:
An inhibitor of cyclin-dependent kinase, stress-induced p21<sup>Waf-1/Cip-1</sup>, mediates hepatocyte mito-inhibition during the evolution of cirrhosis
Authors: John G. Lunz, Hirokazu Tsuji, Isao Nozaki, Noriko Murase, Anthony J. Demetris
Journal: Hepatology (2005)

During the evolution of cirrhosis, there is a relative decrease in volume percentage of hepatocytes and a relative increase in biliary epithelial cells and myofibroblasts. This is recognized histopathologically as a ductular reaction and leads to gradual distortion of the normal hepatic architecture. The final or decompensated stage of cirrhosis is characterized by a further decline in hepatocyte proliferation and loss of functional liver mass that manifests clinically as ascites, encephalopathy, and other signs of liver failure. In this report, we tested the hypothesis that p21-mediated hepatocyte mito-inhibition accelerates the evolution of cirrhosis using an established mouse model of decompensated biliary cirrhosis, p21-deficient mice, and liver tissue from humans awaiting liver replacement. Despite the same insult of long-term (12-week) bile duct ligation, mice prone to decompensation showed significantly more oxidative stress and hepatocyte nuclear p21 expression, which resulted in less hepatocyte proliferation, an exaggerated ductular reaction, and more advanced disease compared with compensation-prone controls. Mice deficient in p21 were better able than wild-type controls to compensate for long-term bile duct ligation because of significantly greater hepatocyte proliferation, which led to a larger liver mass and less architectural distortion. Mito-inhibitory hepatocyte nuclear p21 expression in humans awaiting liver replacement directly correlated with pathological disease stage and model of end-stage liver disease scoring. In conclusion, stress-induced upregulation of hepatocyte p21 inhibits hepatocyte proliferation during the evolution of cirrhosis. These findings have implications for understanding the evolution of cirrhosis and associated carcinogenesis. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html).
Intra-arterial Histamine in the Treatment of Occlusive Peripheral Arterial Disease
Authors: JOHN A. DIXON, W. J. MERLE SCOTT, MARVIN A. EPSTEIN
Journal: Circulation (1952)

Intra-arterial histamine was found to increase significantly the walking tolerance of a small series of cases of obliterative peripheral arterial disease with intermittent claudication. Physiologic determinations during injection show tachycardia, increased cardiac output, increased stroke volume and increased homolateral femoral arteriovenous oxygen difference. The similarity of these results to those caused by arteriovenous fistulas is noted.
Systematic Review: Accuracy of Anti–Citrullinated Peptide Antibodies for Diagnosing Rheumatoid Arthritis
Authors: Penny F. Whiting, Nynke Smidt, Jonathan A.C. Sterne, Roger Harbord, Anya Burton, Margaret Burke, Rebecca Beynon, Yoav Ben-Shlomo, John Axford, Paul Dieppe
Journal: Annals of Internal Medicine (2010)

Background: Early recognition and treatment of rheumatoid arthritis is important to prevent irreversible joint damage. Anti–citrullinated peptide antibodies (ACPA) have been suggested for early diagnosis. Purpose: To compare the accuracy of ACPA and rheumatoid factor in diagnosing rheumatoid arthritis in patients with early symptoms of the disease. Data Sources: 10 medical databases from inception to September 2009, with no language or publication restrictions, and references of included studies. Study Selection: Two independent reviewers screened searches. Full articles were assessed by one reviewer and checked by a second reviewer to identify studies that reported 2 × 2 data on ACPA for the diagnosis of rheumatoid arthritis (by 1987 American College of Rheumatology criteria). Data Extraction: One reviewer abstracted data on patient characteristics, ACPA details, and 2 × 2 data and assessed study quality by using the QUADAS tool. A second reviewer checked extractions. Data Synthesis: 151 studies were included, with considerable heterogeneity in sensitivity (range, 12% to 93%) and specificity (range, 63% to 100%). In cohort studies that investigated second-generation anti–cyclic citrullinated peptide antibodies (anti-CCP2) in patients with early rheumatoid arthritis (<2 years), summary sensitivity and specificity were 57% (95% CI, 51% to 63%) and 96% (CI, 93% to 97%), respectively. Case–control and cross-sectional studies and studies of patients with established rheumatoid arthritis all overestimated sensitivity. Anti-CCP2 had greater specificity than rheumatoid factor (96% vs. 86%), with similar sensitivity. Evidence was insufficient to ascertain whether the combination of anti-CCP2 and rheumatoid factor provides additional benefit over anti-CCP2 alone. Limitations: Most studies used a diagnostic case–control design, which overestimated sensitivity. Items relating to study quality were rarely reported. Publication bias could not be assessed. Conclusion: Anti-CCP2 should be included in the work-up of patients with early symptoms of rheumatoid arthritis. Primary Funding Source: United Kingdom Medical Research Council.
The transcription factor HoxB5 stimulates vascular remodelling in a cytokine-dependent manner
Authors: Anne Fessner, Jennifer S. Esser, Franziska Bluhm, Sebastian Grundmann, Qian Zhou, Cam Patterson, Christoph Bode, Martin Moser
Journal: Cardiovascular Research (2013)

Proper blood vessel formation is essential in health and is often dysregulated in ischaemic diseases. Therefore, regulatory mechanisms that control angiogenesis and arteriogenesis are required to improve treatment of ischaemic diseases. The aim of this study was to investigate the role of homeobox transcription factor HoxB5 overexpression during revascularization in ischaemic disease. To assess the effect of HoxB5 overexpression on blood vessel formation in vivo, we subjected C57BL/6 mice to femoral artery ligation with local intramuscular injection of HoxB5 or green fluorescent protein control adenoviral vectors. Laser Doppler perfusion imaging revealed that HoxB5 enhanced perfusion restoration in mice and immunohistochemistry analysis revealed increased capillary density. To identify a potential mechanism of HoxB5 in blood vessel formation, a 'proteome-profiler' array was performed. HoxB5 overexpression in endothelial cells increased the expression of pro-inflammatory molecules such as monocyte chemotactic protein-1 (MCP-1) and interleukin-6 (IL-6) in vitro and in vivo. Functionally, HoxB5 enhanced monocyte as well as endothelial cell migration in vitro and increased leucocyte infiltration into ischaemic tissues. HoxB5-induced migration of monocytes was antagonized by the presence of an MCP-1 blocking antibody. Our data suggest that overexpression of HoxB5 enhances blood vessel perfusion in vivo by up-regulation of MCP-1 and IL-6 as well as in enhanced leucocyte infiltration and blood vessel remodelling.
Structure of the Adrenergic and Related Receptors
Authors: B F O'Dowd, R J Lefkowitz, M G Caron
Journal: Annual Review of Neuroscience (1989)

The isolation and sequencing of a number of G protein-coupled receptors has now provided extensive primary structure information for this family of homologous proteins. The diverse nature of these receptors suggests that the family of proteins may grow to include receptors for many neurotransmitters and perhaps many peptide hormones. The topography of these receptors, a single polypeptide with seven transmembrane segments, appears to have features well suited for the transmission of signals, via conformational changes, to the interior of the cell. Detailed site-directed mutagenesis studies are now underway in many laboratories to understand the significance of the topography and also the regions of homology evident in the structures of all of these receptors. Obvious features of interest are the precise residues involved in the coupling of the receptors to the G-proteins and the identification of the residues required for ligand binding in each of the receptors, as well as domains of these receptors involved in the regulation of receptor function. In addition, the availability of molecular probes for this family of proteins will permit the elucidation of mechanisms of regulation at the gene level.
THE RESPONSIBILITIES OF SURGERY.CHAIRMAN'S ADDRESS BEFORE THE SECTION ON SURGERY AND ANATOMY, AT THE FIFTY-SIXTH ANNUAL SESSION OF THE AMERICAN MEDICAL ASSOCIATION, PORTLAND, ORE., JULY 11-14, 1905.
Authors: MAURICE H. RICHARDSON
Journal: JAMA (1905)

In this communication I wish, in the first place, to pay a warm tribute to the splendid work that is being done in this country by the surgical profession; and I wish to emphasize particularly the value of the contributions from the country surgeon as distinguished from the metropolitan surgeon. That a populous community is not indispensable for the development of the best and the highest the little town of Rochester, Minn., has most brilliantly demonstrated. The educated, well-balanced, conservative man, considerate of others and of himself, will find in every community abundant opportunities for the highest professional attainments; and he will there make himself a power for good and an honor to his profession. It has seemed to me, especially in the past few years, as I have been brought in contact with physicians and patients in widely separated communities, that the time has come when we must consider
IRISH POOR-LAW REFORM, WITH SUGGESTIONS FOR THE CONSIDERATION OF THE VICEREGAL COMMISSION
Authors: E. Thompson
Journal: BMJ (1903)

The accQmpanying illustration clearly shows the form of a model ear which has been con- structed by Mr. Davidson, of-140, Great Portland Street, aided by some suggestions from me.It is made of a composition which lends itself to the necessary manipulation.A slit is cut in the wall of the meatus, so that the discs containing lithographic reproductions of various conditions of the membrane and the middle ear can be readily inserted.Two model 1-7 o~~~~-X, p.- ears, a right and a left, are supplied.The series of illustra- tions c'omprises 25 fOr the right ear and 25 for the left.Among the conditions illustrated are the normal drum membrane, inflamed conditions, retraction, 'opacities, perforations, etc.The-drawings have all been done by Mrs. Davidson from material which I placed At her disposal.'A bra'ss stand, which Is jointed to allow of the ear being tilted to-the desired angle, Isfxeb a clamp to a table.The auricle is drawn upwards ,n backards, and the -inspection is mnade with the aid of tefrontal mirror orih oocoe -A Health Tent.-essrs.S. Wilson and Co., Bedford Street, B1elfast, maake a tent which is especially useful where it is dsirable to employ tents for invalids.It is double, with 6 in.between the outer and inner tent, thus making it warm in winter andL cool in ~summe-r, and allowing of ventilation with- Ottt draught.The special point about the tent, however, is Mji' invention whereby the canvasg. is kept taut'and a centre pole obviated by the employment of stretchers ad cross stays.It thus, we are assured,-remains'firm without the zi666ssity of constant attention to ~tightening and slackin'g .. ,which the ordinary tent demands.-PATHOLOGICAL SOIEY FLONDON.-At the laboratory V.eeting of this Society, held at King's College, on Tuesday, NOVember 17th, Pro.fessor R. T. HEWLETT 4n the chair the fol- i,.i4Bg-.-eommtimieations-were made :-
Recognising and responding to acute illness in adults in hospital: summary of NICE guidance
Authors: Mary Armitage, Jane Eddleston, Tim Stokes
Journal: BMJ (2007)

Patients in hospital are at risk of becoming acutely ill due to their underlying diagnosis, associated comorbidities, and increasing age and the increasing complexity of care delivered in our hospitals. The recognition of deteriorating health by clinical staff is often delayed or managed inappropriately, resulting in late referral to critical care, avoidable intensive care admissions, and many unnecessary patient deaths.1 This article summarises the most recent guidance from the National Institute for Health and Clinical Excellence (NICE) on improving the recognition and response to acute illness in adults in hospital.2 NICE recommendations are based on systematic reviews of best available evidence. When minimal evidence is available, a range of consensus techniques is used to develop recommendations. In this summary, recommendations derived primarily from consensus techniques are indicated with an asterisk (*). ### Initial assessment Adult patients in acute hospital settings, including patients in the emergency department for whom a clinical decision to admit has been made, should have: Staff undertaking these procedures should be trained to record these observations, understand their clinical relevance, and act upon them.* As a minimum, the following physiological observations should be recorded at the initial assessment and as part of routine monitoring:* ### Routine monitoring
The Waist-to-Hip Ratio as an Index of Central Obesity
Authors: Henry S. Kahn
Journal: JAMA (1996)

<h3>To the Editor.</h3> —Drs Young and Gelskey<sup>1</sup>have offered persuasive evidence that the waist-to-hip ratio (WHR), a traditional index of central obesity, is a weak predictor of metabolic risk. However, it does not necessarily follow that noncentral obesity is a strong predictor of cardiovascular disease. Despite its historical role in focusing attention on abdominal (central) adipose tissue, the WHR may not be an effective anthropometric method for defining central obesity. Cross-sectional studies<sup>2-4</sup>have repeatedly demonstrated that alternative indexes of central obesity (eg, waist-to-thigh ratio, waist circumference alone, sagittal abdominal diameter) are more strongly associated than the WHR with blood pressure and metabolic variables. Beyond correlations with cardiovascular risk factors, it remains to be seen which index of central obesity best predicts cardiovascular disease outcomes.<sup>5</sup> Young and Gelskey have struggled possibly with a straw man of WHR, but they did not confront newer ways of looking at central
Tc-99m Human Serum Albumin Lymphoscintigraphy With SPECT/CT in Chylothorax
Authors: Daiki Kayano, Junichi Taki, Hiroshi Wakabayashi, Seigo Kinuya
Journal: Clinical Nuclear Medicine (2011)

A 45-year-old man who had refractory right chylothorax after esophagectomy for esophageal cancer, underwent lymphoscintigraphy with Tc-99m human serum albumin. Focal abnormal uptake was seen in the mid-abdomen on planar image 30 minutes after the tracer injection. SPECT/CT delineated the extent of the accumulation between the anastomotic site and the right pleural effusion area. SPECT/CT effectively detected the site of lymphatic leakage.
Tracheostomy and the Spanish Civil War
Authors: R. Simo
Journal: Journal of the Royal Society of Medicine (2002)

As a Catalan and having a special interest in the subject, I agree with Dr Coni (March 2002 JRSM1) that most of the medical advances were made by the Republicans rather than the Nationalists. As he says, this was partly because of the more liberal atmosphere of the big Republican cities. Also the looser organization of their Medical Corps may have been more conducive to the development of new ideas. One topic not specifically mentioned by Dr Coni is management of the compromised airway and the performance of emergency tracheostomies. Last summer, I got hold of an excellent book entitled Memories d'un Cirurgia (Memoirs of a Surgeon)2, written by the retired Catalan surgeon Moises Broggi who served in the International Brigades in one of the mobile hospitals. Before the Civil War he was one of the most promising young surgeons in Catalunya; afterwards he decided to stay in Spain but was denied all privileges in one of the university hospitals in Barcelona and could only practise privately for the rest of his professional career. His book, written in a very plain and simple style, became one of the best-sellers in the Catalan language in 2001. In it he describes his experience as a surgeon from 1936 to 1939 with the International Brigades from Brunete to Guadarrama, Belchite, Teruel and finally to the Battle of the Ebro. During the Battle of Belchite they noticed that casualties with severe facial injuries and fractures were dying shortly after triage, whilst waiting on the stretcher for definitive treatment. The deaths were usually due to aspiration of blood into the airway, so they decided to change their practice and perform emergency tracheostomies as initial action. This gave them the opportunity to suction the airway contents and rapidly restore respiration. After that, they stopped the haemorrhage and stabilized the patient, who could then wait to have his fractures reduced and debridement performed. This simple management sequence, resembling current methods of resuscitation, saved many lives during the subsequent battles of the Civil War and was adopted by Allied surgeons during the Second World War. It is said that, for various reasons, we had to wait more than 60 years before the medical heroes in Spain received proper recognition.
T-cell receptor gene rearrangement analysis: Cutaneous T cell lymphoma, peripheral T cell lymphoma, and premalignant and benign cutaneous lymphoproliferative disorders
Authors: Brian D. Zelickson, Margot S. Peters, Sigfrid A. Muller, Stephen N. Thibodeau, John A. Lust, Lynn M. Quam, Mark R. Pittelkow
Journal: Journal of the American Academy of Dermatology (1991)
Amebiasis: Epidemiologic Studies in the United States, 1971-1974
Authors: Donald J. Krogstad, Harrison C. Spencer, George R. Healy, Neva N. Gleason, Daniel J. Sexton, Charles A. Herron
Journal: Annals of Internal Medicine (1978)

Seven investigations of suspected foci of amebiasis between October 1971 and June 1974 lead to three conclusions. [1] A number of laboratories have vastly overdiagnosed amebiasis and have reported leukocytes in stools as Entamoeba histolytica. Two laboratories found to be in error were in community hospitals, and one was at a teaching hospital associated with a medical school and a school of public health. These three laboratories had been diagnosing more than 1200 cases of amebiasis a year for 20 years. [2] When amebiasis does occur, it is likely to be misdiagnosed. In one outbreak with four cases and three deaths, amebiasis was not diagnosed until two patients had died and another was critically ill. Sporadic cases may be mistakenly diagnosed as ulcerative colitis and inappropriately treated with steroids. [3] Foci of endemic amebiasis continue to exist in the United States, both in institutions and in noninstitutional settings.
GPs and charity draw up plan to improve cancer diagnosis in primary care
Authors: I. Torjesen
Journal: BMJ (2012)

The Royal College of General Practitioners and the charity Cancer Research UK have entered into a five year clinical partnership to try to improve the diagnosis and management of cancer in primary care.

Greg Rubin, professor of general practice and primary care at Durham University, will lead the partnership, which will aim to inform, improve, and innovate the care of patients with cancer in general practice.

Rubin said that primary care had become a much more important part of cancer care in England in recent years as a result of the …
Abstract 3238: Synthesis and evaluation of 17-oximino-estrone derivatives as potential anti-breast cancer agents
Authors: Patrick Joseph, John S. Cooperwood, Zhongliang Wan
Journal: Cancer Research (2011)

Abstract The selective estrogen receptor modulator (SERM) tamoxifen (TAM) is the gold standard used in the treatment of estrogen-dependent breast cancer. Although it significantly benefited women with breast cancer, time-dependent tumor resistance and the risk of endometrium cancer are associated with it. Consequently, there is an urgent need for alternative treatments. PURPOSE: Incorporating the oxime moiety in conjunction with various basic side chains associated with the pharmacophore of the SERMs into estrone may yield various estrone derivatives with antiestrogenic activity. The estrone derivatives were compared to 4-hydroxy-tamoxifen (4-OH-TAM) and raloxifene (RAL). METHODS: The estrone derivatives were synthesized using established chemical procedures. The Southern Research Institute in Birmingham, Alabama carried out the cytotoxicity studies in MCF-7, MDA-MB-231 and Ishikawa cancer cells. They tested different concentrations of the six different estrone derivatives ranging from .01 nM to 100,000 nM on 5000 MCF-7 cells/well, on 5000 MDA-MB-231 cells/well and on 5000 Ishikawa cells/well. Cells pre-treated with the various estrone derivatives were incubated at 37°C for 3 days followed by MTS assay. Their IC50 values were generated using GraphPad Prism 5.0. RESULTS: Our compounds demonstrated anti-proliferative activity in MCF-7 cells but they were not as potent as 4-OH-TAM(2µM) or RAL (3µM). Compounds 2, 3, 4, 6, and 7 (31µM, 29µM, 30µM, 30µM, and 29µM respectively) were comparable in potency to RAL (28µM) in MDA-MB-231 cells but all were not as potent as 4-OH-TAM (22µM). Compounds 3, 6, and 7 (20µM, 20µM, and 17µM respectively) were comparable or greater in potency to 4-OH-TAM (20µM) in Ishikawa cells and compounds 2, 3, 6, and 7 (24µM, 20µM, 20µM, and 17µM respectively) were comparable or greater in potency to RAL (23µM). CONCLUSION: Applying the oxime moiety in conjunction with the pharmacophore of the SERMs to estrone produced agents with antiproliferative activity. They also showed antiproliferative activity in estrogen-receptor negative MDA-MB-231 cells. These results suggest that several of the estrone derivatives show promise as potential anti-breast cancer agents. 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 3238. doi:10.1158/1538-7445.AM2011-3238
How Cloning Could Change Medicine
Authors: Jennifer Fisher Wilson
Journal: Annals of Internal Medicine (2003)

Current Clinical Issues16 September 2003How Cloning Could Change MedicineJennifer Fisher WilsonJennifer Fisher WilsonSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-139-6-200309160-00036 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail When most people hear the word cloning, it conjures images of Dolly the sheep. Dolly, born in 1996, was the world's first clone of a mammal. This event ignited ethical debates because it raised the possibility that a similar process would someday be used for humans. Dolly died earlier this year, and by then the controversy over human cloning was largely decidedmost people, including most scientists and politicians, have agreed that it is neither feasible nor desirable, let alone ethical. But a related debate about therapeutic cloningthe use of somatic cell nuclear transfer to produce embryonic stem cells (see Glossary ... Author, Article, and Disclosure InformationAuthors: Jennifer Fisher Wilson PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAdministrative and research policies required to bring cellular therapies from the research laboratory to the patient's bedside 16 September 2003Volume 139, Issue 6Page: 535-538KeywordsAdult stem cellsCell culturesCloningEmbryonic stem cellsEmbryosForecastingRegenerative medicineScientistsStem cell linesStem cells ePublished: 16 September 2003 Issue Published: 16 September 2003 Copyright & PermissionsCopyright © 2003 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...