tbuckley/cabot-search huggingface dataset:
Gene Evolution v Special Creation
Authors: Terry W. Bell
Journal: JAMA (1983)

<h3>To the Editor.—</h3> The recent article entitled "Mechanisms of Gene Evolution" by Leder (1982;248:1582) details the remarkable achievements that have been made in molecular genetics. However, the article content is based on the assumption that gene evolution is a fact and not an unprovable theory. Conversely, an elegant and detailed description of gene homologies is also cogent support for a common design fundamental to all forms of life. One of the most widely used methods to support molecular evolution is the classic phylogenetic tree based on amino acid sequences in cytochrome c of various species. Yet, it is usually ignored that the tree supporting an evolutionary interpretation is only one of 40 such trees generated by a computer and that it is chosen because it most closely fits "known phylogeny" or assumed evolutionary history.<sup>1</sup>Even this tree shows serious discrepancies such as the turtle being more closely related to
The "Holiday Heart": Electrophysiologic Studies of Alcohol Effects in Alcoholics
Authors: ARNOLD J. GREENSPON
Journal: Annals of Internal Medicine (1983)

Although the "holiday heart syndrome," highlighted by rhythm disturbances after acute alcohol ingestion, is well known, the potential arrhythmogenic effects of alcohol have not been studied. Fourteen patients (two with congestive cardiomyopathy) with a history of rhythm disturbances and alcohol consumption were studied electrophysiologically. One patient had nonsustained ventricular tachycardia, one had nonsustained atrial fibrillation, one had paired ventricular responses, and the remainder had no response to the extrastimulus technique. After 90 mL of 80-proof whiskey, 10 of the 14 patients developed sustained or nonsustained atrial or ventricular tachyarrhythmias. Significant prolongation of His-ventricular conduction was seen after alcohol intake; this was noteworthy as one of the patients had previously shown Mobitz II atrioventricular block after acute alcohol consumption. Alcohol in modest doses has the potential to produce rhythm disturbances in patients with a history of chronic alcohol consumption and heart disease.
Hepatitis B virus (HBV) sequence variation of cytotoxic T lymphocyte epitopes is not common in patients with chronic HBV infection.
Authors: B Rehermann, C Pasquinelli, S M Mosier, F V Chisari
Journal: Journal of Clinical Investigation (1995)

It has been suggested that immune selection pressure exerted by the cytotoxic T lymphocyte (CTL) response could be responsible for viral persistence during chronic hepatitis B virus infection. To address this question, in the current study we compared the DNA and amino acid sequences of, and the CTL responses to, multiple HLA-A2-restricted CTL epitopes in the hepatitis B virus in several HLA-A2-positive patients with acute and chronic hepatitis. Our results indicate that the CTL response to these epitopes is barely detectable in the majority of patients with chronic hepatitis. Further, we show that the weak CTL response is not secondary in infection by mutant viruses lacking these epitopes, and we show that the CTL response did not select for escape mutants in any of these patients. We conclude that an ineffective hepatitis B virus specific CTL response is the primary determinant of viral persistence in chronic hepatitis and that immune selection of viral variants is not a common event in the majority of patients.
Effects of A1 adenosine receptor overexpression on normoxic and post-ischemic gene expression
Authors: Kevin J Ashton, Kirsty Holmgren, Jason Peart, Amy R Lankford, G Paul Matherne, Sean Grimmond, John P Headrick
Journal: Cardiovascular Research (2003)

Objectives: To identify potential molecular genetic determinants of cardiovascular ischemic tolerance in wild-type and transgenic hearts overexpressing A1 adenosine receptors (A1ARs). Methods: cDNA microarrays were used to explore expression of 1824 genes in wild-type hearts and ischemia-tolerant mouse hearts overexpressing A1ARs. Results: Overexpression of A1ARs reduced post-ischemic contractile dysfunction, limited arrhythmogenesis, and reduced necrosis by ∼80% in hearts subjected to 30 min global ischemia 60 min reperfusion. Cardioprotection was abrogated by acute A1AR antagonism, and only a small number (19) of genes were modified by A1AR overexpression in normoxic hearts. Ischemia-reperfusion significantly altered expression of 75 genes in wild-type hearts (14 induced, 61 down-regulated), including genes for metabolic enzymes, structural/motility proteins, cell signaling proteins, defense/growth proteins, and regulators of transcription and translation. A1AR overexpression reversed the majority of gene down-regulation whereas gene induction was generally unaltered. Additionally, genes involved in cell defence, signaling and gene expression were selectively modified by ischemia in transgenic hearts (33 induced, 10 down-regulated), possibly contributing to the protected phenotype. Real-time PCR verified changes in nine selected genes, revealing concordance with array data. Transcription of the A1AR gene was also modestly reduced post-ischemia, consistent with impaired functional sensitivity to A1AR stimulation Conclusions: Data are presented regarding the early post-ischemic gene profile of intact heart. Reduced A1AR transcription is observed which may contribute to poor outcome from ischemia. A1AR overexpression selectively modifies post-ischemic gene expression, potentially contributing to ischemic-tolerance.
Abstract 3229: Biomarker validation for a rare malignancy in a mouse model
Authors: Elliot L. Servais, Christos Colovos, Kei Suzuki, Luis Rodriguez, Cami Sima, Valerie W. Rusch, Michel Sadelain, Prasad S. Adusumilli
Journal: Cancer Research (2010)

Abstract Purpose: Malignant pleural mesothelioma (MPM) is a rare malignancy often diagnosed at an advanced stage. Clinical validation of a biomarker that would allow for earlier diagnosis as well as detection of recurrence following therapy is limited by the rarity of the tumor. Soluble mesothelin-related peptide (SMRP), which can be detected in patients’ serum, is a cleavage product of mesothelin, a tumor-associated cell surface protein over-expressed in &amp;gt;80% of MPMs. The purpose of this study is to validate the pharmacodynamics of SMRP as a tumor biomarker of prognosis and therapy response using a clinically and pathologically relevant orthotopic xenograft model of MPM. Experimental Design: Orthotopic MPM xenograft mice (athymic nude and SCID-beige) were established by direct pleural injection of human mesothelioma cells (MSTO-211H) retrovirally transduced to stably express mesothelin and the GFP-Firefly Luciferase fusion gene. Quantitative bioluminescence imaging (BLI) and MRI were used to serially monitor tumor burden and progression and were correlated with serum SMRP levels (Mesomark® ELISA assay). Kaplan-Meier survival analyses were performed following xenografting of mesothelin and non-mesothelin expressing tumors. The utility of SMRP as a biomarker of therapeutic response was validated by treating MPM mice with either: (a) Cisplatin (4mg/kg IP weekly), (b) thoracic radiation (20Gy total in 5 fractions), (c) combination chemoradiation, or (d) no treatment and correlating serial SMRP levels to survival and BLI signal. Results: MPM cells secreting SMRP demonstrated increased invasion and migration in vitro as assessed by the modified Boyden Chamber assay compared to cells without SMRP secretion, 124 vs 48 cells per high-powered field (p&amp;lt;0.0001) and 49 vs 32 cells (p=0.017), respectively. In MPM xenograft mice, increasing SMRP levels correlated with tumor progression by quantitative BLI (spearman r=0.89, p=0.04) and decreased survival (p=0.001). SMRP demonstrated improved sensitivity for detecting early MPM tumors compared to MRI. SMRP levels significantly decreased following treatment versus control mice (p=0.03) and were predictive of survival (hazard ratio = 4.5, 95%CI 1.53-13.1). In addition, SMRP detected tumor recurrence following treatment earlier than MRI. Conclusions: We have shown that a serum biomarker of tumor progression and therapy response can be successfully studied in a clinically relevant animal model. To our knowledge, this is the first report utilizing BLI as a reproducible tool, in conjunction with an orthotopic animal model, to quantitatively assess pleural tumor burden and biomarker pharmacodynamics. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3229.
Millions more at risk of arsenic poisoning than previously thought
Authors: S. Kumar
Journal: BMJ (2003)

The number of people at risk of arsenic poisoning from drinking water from sunken wells may be considerably higher than previously thought, a new report from the University of Calcutta has said.

The first cases of arsenic poisoning in the Indian subcontinent were reported in India in 1983, and it has been known for several years that half the population of Bangladesh and many residents of West Bengal state were at risk ( BMJ 2000;320:822). Now the danger is thought to extend beyond these areas.

“Almost 330 million people may be at risk in India and Bangladesh compared to 150 million as believed earlier,” says Dipankar Chakraborti of the School of Environmental Sciences, Jadavpur University, …
The Hemolytic-Uremic Syndrome Is a Syndrome
Authors: Bernard S. Kaplan, Keith N. Drummond
Journal: New England Journal of Medicine (1978)

The article in this week's issue of the Journal by Koster and his colleagues raises important questions not only about the pathogenesis of the hemolytic-uremic syndrome but, perhaps more importantly, about the clinical conditions that can reasonably be included under this rubric.Since the description some 20 years ago by Gasser and his associates of a syndrome comprising acute hemolytic anemia, thrombocytopenia and renal insufficiency, ample evidence has been adduced from clinical, epidemiologic, histopathological and ultra-structural studies to permit the conclusion that this constellation of findings may occur in a number of distinctly different situations and in all likelihood is . . .
IgE and IgE-rheumatoid factors in circulating immune complexes in rheumatoid arthritis.
Authors: K Meretey, A Falus, C C Erhardt, R N Maini
Journal: Annals of the Rheumatic Diseases (1982)

The sera of 21 patients with rheumatoid arthritis (RA), 11 patients with systemic lupus erythematosus (SLE), and 20 healthy subjects were analysed for the presence of IgE in immune complex fractions. These fractions were isolated by polyethylene glycol precipitation and gel filtration. Thirteen sera from RA patients contained IgE immune complexes (IC) and 11 of these were from patients with extra-articular manifestations. One SLE and none of the control sera contained such material. The serum IgE level did not correlate with IgE content of the IC fractions. Higher mean serum IgE levels were found in RA patients with extra-articular complications than in controls or RA patients with joint disease only, but the differences did not reach statistical significance. IgE anti-rabbit IgG (IgE rheumatoid factors) could be demonstrated in some IgE positive IC fractions. Antibodies to IgE, in 2 instances characterised as belonging to IgG class, were also found in ICs. This suggests the presence of anti IgE complexes. It is suggested that IgE, including some with rheumatoid factor activity, is contained in complexes which may be involved in some extra-articular manifestations of RA.
THE EXTERNAL TREATMENT OF ACUTE VESICULAR ECZEMA.Read in the Section of Dermatology and Syphilography, at the Forty-third Annual Meeting of the American Medical Association, held at Detroit, Mich., June, 1892.
Authors: LOUIS A. DUHRING
Journal: JAMA (1893)

There is no cutaneous disease in the acute stage that the general practitioner is called upon to treat more frequently than eczema. In one variety or another in its earliest manifestations he is continually meeting with it, inasmuch as it falls to his lot rather than to that of the specialist. The latter, in private practice at least, seldom has the opportunity of observing the disease in the first stage, and rarely until some application, soothing or irritating, has been employed. Frequently it is the latter kind of remedy that has been applied, thus augmenting the already actively inflamed cutaneous surface, increasing cell proliferation and exudation, serous or plastic, as the case maybe. Such examples of acute eczema, undoubtedly aggravated by the application used, injudicious as to the remedy itself, or, as is often the case, as to the strength, frequently find their way to the specialist. It is with
RADIATION IN THE TREATMENT OF CARCINOMA OF THE BODY OF THE UTERUS
Authors: A. N. ARNESON
Journal: JAMA (1941)

Analysis of clinical results obtained in carcinoma of the body of the uterus has revealed two factors of fundamental importance in the treatment of operable cases. The first is that hysterectomy alone is inadequate treatment for certain types of clinically operable patients. The second point is that average results can be improved by combining radiation with surgery. Several authors have demonstrated a close relationship between microscopic appearance of tumor and end results. Collected statistics for hysterectomy alone given in an earlier publication show a greater percentage of five year cures among the well differentiated lesions than in the more anaplastic varieties.<sup>1</sup>More recent data presented by Scheffey and Thudium,<sup>2</sup>Ward and Sackett,<sup>3</sup>Healy and Brown<sup>4</sup>and others illustrate the importance of combining radiation with surgery in the attempt to improve clinical results, particularly among lesions of histologic types known to have a less favorable prognosis. For
Serum aminoterminal propeptide of type III procollagen in psoriasis and psoriatic arthritis: Relation to liver fibrosis and arthritis
Authors: Hugh Zachariae, Hafiz Muhammad Aslam, Peter Bjerring, Helmer Søgaard, Eva Zachariae, Lene Heickendorff
Journal: Journal of the American Academy of Dermatology (1991)
Abstract 4107: Possible role of autophagy inhibition in hypoxia-induced chemoresistance of pancreatic cancer cells
Authors: Yoon Ho Ko, Hye Sung Won, Eun Kyoung Jeon, Young Seon Hong, Young-Seok Cho
Journal: Cancer Research (2012)

Abstract BACKGROUND: Autophagy is a catabolic process and provides metabolic support for the cell by degradation of intracellular macromolecules. Various types of stress, including hypoxia, activate autophagy. Recent studies have suggested that hypoxia has been shown to associate with resistance to chemotherapy and radiotherapy and hence poor prognosis in pancreatic cancer. This study investigated the role of autophagy in the treatment of pancreatic cancer with gemcitabine under hypoxic condition. METHODS: To evaluate the role of autophagy inhibition in hypoxia-induced chemoresistance, BxPC-3 human pancreatic cancer cell line was used under normoxic and hypoxic conditions. We evaluated the extent of LC3-II, as an autophagosome marker, by Western blotting to measure the hypoxia- or chemotherapy-induced autophagy. We then examined the effects of gemcitabine on induction of apoptosis under normoxic and hypoxic conditions. Finally, to determine the effect of 3-MA, a known inhibitor of autophagy, on overcoming hypoxia-induced chemoresistance, the MTS assay and flow cytometry were performed.RESULTS: Compared with normoxia, gemcitabine-induced cell death was significantly decreased under hypoxia, as a result of the reduced apoptosis. Western blotting analysis demonstrated that LC3-II was increased under hypoxia, compared with normoxia. However, we found that 3-MA can enhance the growth inhibition and apoptotic effect of gemcitabine, even under hypoxia. These findings mean that autophagy mediates the chemoresistance under hypoxia. Conclusions: Activated autophagy plays a role in hypoxia-induced chemoresistance of pancreatic cancer cells. These findings may have important implications for future therapeutic strategies using gemcitabine against pancreatic cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4107. doi:1538-7445.AM2012-4107
Drug induced Parkinson's disease.
Authors: J Williamson
Journal: BMJ (1984)

Disorders, and Pain in the Neck.These are free and can be sent in bulk to general practitioners and hospital doctors or individually to patients.Special booklets for the parents and teachers of children with juvenile arthritis, When Your Child Has Arthritis and When A Young Person Has Arthritis, have also been produced.Other booklets-Your Home and Your Rheumatism, Marriage, Sex and Arthritis, and Are You Sitting Comfortably?-are available at a modest cost.
ADHD, comorbidity, synaptic gates and re-entrant circuits
Authors: Florence Levy
Journal: Behavioral and Brain Sciences (2005)

the “dynamic developmental” theory of attention-deficit/hyperactivity disorder (adhd) has come full circle from wender's (1971) reinforcement hypothesis. by specifying the principle of time constraints on reinforcement and extinction, the present theory allows for empirical validation. however, the theory implies, but does not discuss, implications for the neurophysiology of comorbidity in adhd. the authors' attribution of comorbid oppositional behavior to parental and societal reinforcement leaves out biological factors.
Regional Results of Acute Appendicitis Care
Authors: Don E. Detmer
Journal: JAMA (1981)

In 1978, acute appendicitis care was reviewed by studying 2,375 cases from 74% of all hospitals in Wisconsin outside the greater Milwaukee area. The mortality was 0.17% and the wound complication rate was 5.3%. A normal appendix report was noted in 14% of all cases; female patients accounted for 60% of these cases, and only 44.5% of the total study population. The rupture or perforation rate was 13.4%; 62% of these problems occurred in male patients. The mean hospital stay was 5.4 days; for perforated cases, it was 10.2 days. An analysis that compared hospitals by their individual ratios of normal appendices to perforations favors the conclusion that a small but real decrease in negative appendectomy rates could be achieved without producing more ruptures or perforations.
Role of antiretroviral therapies in mucocutaneous manifestations in HIV-infected children over a period of two decades
Authors: E. Seoane Reula, J.M. Bellon, D. Gurbindo, M.A. Munoz-Fernandez
Journal: British Journal of Dermatology (2005)

Human immunodeficiency virus (HIV) infection causes a severe cellular immunodeficiency, which results in a greater susceptibility to infectious, inflammatory and malignant conditions. Among these, pathologies of the skin seem to be those most frequently observed in HIV+ patients. However, there are few reports on how antiretroviral therapy affects skin disorders in HIV-infected children.To study the incidence and prevalence of skin disorders in a cohort of HIV-infected children, in relation to the antiviral therapy [nontreated, monotherapy, combined therapy and highly active antiretroviral therapy (HAART)] received, and their impact on immunological and virological markers. The treatments were those available in different calendar periods in the history of antiviral treatment.A retrospective, observational study in a cohort of 210 HIV-infected children was carried out. These children were followed up every 3 months throughout 22 years. The viral load (HIV RNA copies mL(-1)) was quantified using reverse transcriptase-polymerase chain reaction and the viral phenotype of HIV-1 isolates was determined by in vitro culture. T-lymphocyte subsets in peripheral blood were quantified by flow cytometry.Mucocutaneous manifestations were diagnosed in 17% of the untreated infected children. Of the treated children in different treatment periods, 22% in the monotherapy period, 25% in the combined therapy period but only 10% on HAART had some type of mucocutaneous manifestation, concordant with a higher number of CD4+ T cells, a lower viral load and less cytopathic virus in the last group. Mucocutaneous manifestations of infectious aetiology were most frequently observed; they were detected in 13% of the children during the first calendar period (untreated children), 16% during the second and third periods (monotherapy and combined therapy) and only 5% in the last period (HAART). Interestingly, syncytium-inducing virus was present in 69% of all children with mucocutaneous manifestations of infectious aetiology.Only in the last calendar period (HAART) was a significant decrease observed in the prevalence of mucocutaneous manifestations with HIV infection associated with an increase in CD4+ T cells. In addition, we found a strong association between children who had mucocutaneous manifestations with an infectious aetiology and a more cytopathic (X4/SI) viral phenotype.
DIAPHRAGMATIC HERNIA OF FUNDUS OF STOMACH THROUGH THE ESOPHAGEAL HIATUS
Authors: L. B. MORRISON
Journal: JAMA (1925)

Literature is replete with articles on the subject of diaphragmatic hernia, giving minute details as to its embryologic anatomy and differential diagnosis. Richards<sup>1</sup>recently discussed it from the point of view of embryology, and Morrison,<sup>2</sup>from that of the differential diagnosis. I shall refrain from discussing these points. and take up the subject principally from the roentgenologic point of view. Several years ago, my associate, Dr. T. R. Healy, and I made a careful roentgen-ray study of the fundus of the stomach, hoping to determine some method whereby malignancy could be earlier diagnosed. My attention was attracted to the varying shapes of the fundus in the upright, prone, supine, lateral and oblique positions, when filled with the barium meal. The position of the esophageal opening into the stomach was noted, as well as the position and movements of the diaphragm, the behavior of the heart and lungs, and
Warning letter not seen by relevant body, Bristol inquiry told
Authors: C. Dyer
Journal: BMJ (1999)

A letter sent in July 1992 to the Royal College of Surgeons of England raising serious concerns about death rates for babies undergoing heart surgery in Bristol was not passed on to the NHS body responsible for deciding whether hospitals should keep their designation as specialist units, the public inquiry into the deaths of children who had had heart surgery at Bristol Royal Infirmary heard last week.

The letter from Dr John Zorab, medical director of the Frenchay Hospital in Bristol, was sent to Sir Terence English, who had just finished his term as president of the royal college.

Sir Terence was a member of the supraregional services advisory group, which designated …
GMC proposes radical changes to registration
Authors: R. MacDonald
Journal: BMJ (2003)

“Limited registration should be abolished and replaced with a single licensing system covering all doctors, irrespective of whether they have qualified in the UK, EEA [European Economic Area] or overseas,” proposes a recent consultation document from the General Medical Council.

This is one of several radical proposals resulting from the GMC's fundamental review of its registration arrangements, which currently number six different types. Limited registration is presently granted to non-EEA doctors at the discretion of the GMC.

The document states: “Changes in [the GMC's] regulatory framework and …