tbuckley/cabot-search huggingface dataset:
Characterization of the complement sensitivity of paroxysmal nocturnal hemoglobinuria erythrocytes.
Authors: C J Parker, T Wiedmer, P J Sims, W F Rosse
Journal: Journal of Clinical Investigation (1985)

The affected erythrocytes of paroxysmal nocturnal hemoglobinuria (PNH II and PNH III cells) are abnormally sensitive to complement-mediated lysis. Normal human erythrocytes chemically modified by treatment with 2-amino-ethylisothiouronium bromide (AET) have been used as models for PNH cells inasmuch as they also exhibit an enhanced susceptibility to complement. To investigate the bases for the greater sensitivity of these abnormal cells to complement-mediated lysis, we compared binding of C3 and constituents of the membrane attack complex to normal, PNH II, PNH III, and AET-treated cells after classical pathway activation by antibody and fluid-phase activation by cobra venom factor complexes. When whole serum complement was activated by antibody, there was increased binding of C3 and C9 to PNH II, PNH III, and AET-treated cells, although the binding of these complement components to PNH II and PNH III cells was considerably greater than their binding to the AET-treated cells. In addition, all of the abnormal cell types showed a greater degree of lysis per C9 bound than did the normal erythrocytes. PNH III and AET-treated cells were readily lysed by fluid-phase activation of complement, whereas normal and PNH II erythrocytes were not susceptible to bystander lysis. The greater hemolysis of PNH III and AET-treated cells in this reactive lysis system was due to a quantitative increase in binding of constituents of the membrane attack complex. This more efficient binding of the terminal components after fluid-phase activation of whole serum complement was not mediated by cell-bound C3 fragments. These investigations demonstrate that the molecular events that characterize the enhanced susceptibility of PNH II, PNH III, and AET-treated erythrocytes to complement-mediated lysis are heterogeneous.
Is the Risk of Diabetic Retinopathy Greater in Non-Hispanic Blacks and Mexican Americans Than in Non-Hispanic Whites With Type 2 Diabetes?: A U.S. population study
Authors: Maureen I Harris, Ronald Klein, Catherine C Cowie, Michael Rowland, Danita D Byrd-Holt
Journal: Diabetes Care (1998)

OBJECTIVE To compare the risk for diabetic retinopathy in non-Hispanic white, non-Hispanic black, and Mexican-American adults with type 2 diabetes in the U.S. population. RESEARCH DESIGN AND METHODS Representative population-based samples of people aged ≥ 40 years in each of the three racial/ethnic groups were studied in the 1988–1994. Third National Health and Nutrition Examination Survey (NHANES III). Diagnosed diabetes was ascertained by medical history interview, and undiagnosed diabetes by measurement of fasting plasma glucose. A fundus photograph of a single eye was taken with a nonmydriatic camera, and a standardized protocol was used to grade diabetic retinopathy. Information on risk factors for retinopathy was obtained by interview and standard laboratory procedures. RESULTS Prevalence of any lesions of diabetic retinopathy in people with diagnosed diabetes was 46% higher in non-Hispanic blacks and 84% higher in Mexican Americans, compared with non-Hispanic whites. Blacks and Mexican Americans also had higher rates of moderate and severe retinopathy and higher levels of many putative risk factors for retinopathy. Blacks had lower retinopathy prevalence among those with undiagnosed diabetes. In logistic regression, retinopathy in people with diagnosed diabetes was associated only with measures of diabetes severity (duration of diabetes, HbA1c, level, treatment with insulin and oral agents) and systolic blood pressure. After adjustment for these factors, the risk of retinopathy in Mexican Americans was twice that of non-Hispanic whites, but non-Hispanic blacks were not at higher risk for retinopathy. These risks were similar when people with undiagnosed diabetes were included in the logistic regression models. CONCLUSIONS The prevalence and severity of diabetic retinopathy is greater in non-Hispanic blacks and Mexican Americans with type 2 diabetes in the U.S. population than in non-Hispanic whites. For blacks, this can be attributed to their higher levels of risk factors for retinopathy, but the excess risk in Mexican Americans is unexplained.
Use of breath hydrogen and methane as markers of colonic fermentation in epidemiologic studies: circadian patterns of excretion.
Authors: L Le Marchand, L R Wilkens, P Harwood, R V Cooney
Journal: Environmental Health Perspectives (1992)

Fermentation in the large bowel has been postulated to play a protective role against colon cancer. Hydrogen and methane are end products of this fermentation process and are absorbed into the bloodstream and excreted via expired air in the breath. Breath levels of hydrogen and, to a lesser extent, methane correlate strongly with colonic fermentation and may serve as useful biomarkers for this process. In a preliminary study to assess the usefulness of these two markers in epidemiologic studies, we followed the hourly excretion of the two gases in expired alveolar air for 48 hr in 20 healthy subjects, using a Quintron gas chromatograph equipped with a solid-state detector specific for reducing gases. All subjects excreted hydrogen, but 71% did not excrete methane. Possible atmospheric contamination of the samples was corrected for on the basis of breath carbon dioxide levels. A clear circadian pattern of excretion was observed for breath hydrogen, with a decrease during the early morning followed by a progressive increase during the rest of the day. Methane excretion was constant throughout the day. This study shows that four samples collected at convenient times (0600, 1300, 1800, and 2200 hr) are optimal to characterize individuals by their breath excretions of hydrogen and methane during a 24-hr period.
Teaching within the Hospital — The Role of Full-Time and Part-Time Faculty
Authors: Robert H. Ebert
Journal: New England Journal of Medicine (1964)

IT is difficult to define the role of full-time and part-time faculty in the teaching of house staff within the hospital without first examining the nature and purpose of that educational process. This in turn requires a brief look at medical education in the United States because to examine house-officer training intelligently, one must know how it relates to the education of the medical student.Relation of Medical-School Education to Postgraduate EducationThe fact that a medical school requires hospitals and clinics for its "classrooms" and "laboratories" places it in a curious relation to other university schools. It is hard . . .
312 Evaluation of angiotensinogen -6G&gt;A and M235T single nucleotide polymorphisms as inherited risk factors for the progression of chronic liver disease of different etiologies
Authors: J. Halangk, T. Berg, G. Puhl, T. Muller, O. Landt, B. Wiedenmann, P. Neuhaus, W. Luck, H. Witt
Journal: Journal of Hepatology (2004)
The amelioration of cartilage degeneration by ADAMTS-5 inhibitor delivered in a hyaluronic acid hydrogel
Authors: Pengfei Chen, Shouan Zhu, Yanyan Wang, Qin Mu, Yan Wu, Qingqing Xia, Xiaolei Zhang, Heng Sun, Jiadong Tao, Hu Hu, Ping Lu, Hongwei Ouyang
Journal: Biomaterials (2014)
Constraining Ligand-Binding Site Stoichiometry Suggests that a Cyclic Nucleotide–Gated Channel Is Composed of Two Functional Dimers
Authors: David T. Liu, Gareth R. Tibbs, Pierre Paoletti, Steven A. Siegelbaum
Journal: Neuron (1998)

Cyclic nucleotide-gated ion channels are composed of four pore-forming subunits. Binding of cyclic nucleotide to a site in the intracellular carboxyl terminus of each subunit leads to channel activation. Since there are four subunits, four binding events are possible. In this study, we investigate the effects of individual binding events on activation by studying channels containing one, two, three, or four functional binding sites. The binding of a single ligand significantly increases opening, although four ligands are required for full activation. The data are inconsistent with models in which the four subunits activate in a single concerted step (Monod-Wyman-Changeux model) or in four independent steps (Hodgkin-Huxley model). Instead, the four subunits may associate and activate as two independent dimers.
Response to Open Peer Commentaries on “Gunther von Hagens’ BODY WORLDS: Selling Beautiful Education”: Signed, Sealed, Delivered
Authors: Lawrence Burns
Journal: The American Journal of Bioethics (2007)

Click to increase image sizeClick to decrease image size Notes 1Gunther von Hagens, "Two Cold War Symbols in New Bond Film" (http://www.bodyworlds.com/en/prelude/james_bond.html; accessed 8 February 2007). 2One notable exception is Myers (2007), who reads the signature as an affirmation of the "heterotropic gaps" in public education.
Fiberendoscopic Foreign Body Removal from the Upper Gastrointestinal Tract
Authors: W. Rösch, M. Classen
Journal: Endoscopy (1972)

Report on fiberendoscopic foreign body removal from esophagus, stomach and duodenum in children, mentally handicapped patients and normal adults. Using forceps or snare many foreign bodies, even major items, can be extracted. A trial of operative fiberendoscopy should be given to all patients with ingested foreign bodies which stay for a longer period of time in the stomach thereby saving the patient gastrotomy.
Citrate compared to low molecular weight heparin anticoagulation in chronic hemodialysis patients
Authors: Martien J.F.M. Janssen, Jeroen K. Deegens, Theodoor H. Kapinga, Johan R. Beukhof, Peter C. Huijgens, Arie C. van Loenen, Jan van der Meulen
Journal: Kidney International (1996)
New scheme for staff shortages
Authors: P. N. Trewby
Journal: BMJ (2010)

Rather than use locums,1 hospital trusts could establish “trust posts” and use the Medical Training Initiative (MTI) scheme to fill them.2 The savings on locum costs would more than fund the salaries of the additional doctors.

The MTI scheme was established in 2009 to provide well qualified enthusiastic overseas doctors to work and train …
Very Early Noninvasive Detection of Acute Experimental Nonreperfused Myocardial Infarction With <sup>99m</sup> Tc-Labeled Glucarate
Authors: Jagat Narula, Artiom Petrov, Koon-Yan Pak, Bradford C. Lister, Ban-An Khaw
Journal: Circulation (1997)

Background 99m Tc glucarate has recently been reported to be an infarct-avid agent. The feasibility of imaging with 99m Tc glucarate was evaluated for the early diagnosis of nonreperfused and reperfused myocardial infarction and compared with localization of simultaneously administered 111 In anti-myosin. Methods and Results Four groups of six rabbits each were studied. The left anterior descending coronary artery (LAD) was kept persistently occluded (n=6) or reperfused after 40 minutes (n=6) in rabbits. After confirmation of LAD occlusion by 201 Tl scintigraphy, a mixture of 99m Tc glucarate (15.7±1.6 mCi) and 111 In anti-myosin (0.53±0.03 mCi) was administered intravenously. Another group of rabbits (n=6) with 5 or 15 minutes of LAD occlusion were used to assess the affinity of 99m Tc glucarate for the ischemic myocardium. The remaining 6 rabbits with reperfused myocardial infarction were used for the assessment of subcellular localization of 99m Tc glucarate. 99m Tc glucarate cleared rapidly from circulation (elimination t 1/2 , 36 minutes). Infarcts were visualized within 10 minutes in reperfused and within 30 minutes in nonreperfused coronary territories after intravenous administration. 111 In anti-myosin delineated reperfused infarcts within 1 to 3 hours, but no uptake was seen in persistently occluded rabbits. 99m Tc glucarate uptake in reperfused and nonreperfused infarct centers was 28 and 12 times greater, respectively, than that in normal myocardium ( P =.0001). A direct correlation between glucarate and anti-myosin localization ( r =.60 for nonreperfused; 0.76 for reperfused; P &lt;.0001) was observed. Ischemic hearts showed no glucarate uptake. Subcellularly, 99m Tc glucarate localized predominantly in the nuclear fraction of the infarct, with lesser extents in the mitochondrial and cytoplasmic fractions. Conclusions Noninvasive imaging of myocardial infarcts with 99m Tc glucarate is possible within minutes in persistently occluded or reperfused myocardial infarcts. Early detectability results from the rapid blood clearance and high avidity of glucarate for the acutely necrotic myocardial tissue.
AORTIC STIFFNESS, IN ADDITION TO MYOCARDIAL SCARRING AND MITRAL REGURGITATION, INCREMENTALLY PREDICTS OUTCOMES IN SEVERE ISCHEMIC CARDIOMYOPATHY PATIENTS
Authors: Ashley M. Lewis, Deborah H. Kwon, Zoran B. Popovic, Carmel M. Halley, Paul Schoenhagen, Scott D. Flamm, Brian P. Griffin, Randall C. Starling, Milind Y. Desai
Journal: Journal of the American College of Cardiology (2010)
539. Antitumor Activity of an hTERT-Specific, GFP Expressing Oncolytic Adenovirus
Authors: John J. Davis, Li Wang, Lidong Zhang, Wei Guo, Fuminori Teraishi, Kai Xu, Lin Ji, Bingliang Fang
Journal: Molecular Therapy (2005)

Oncolytic viruses are designed to selectively replicate and lyse tumor cells by using mutations that restrict the lytic viral cycle to tumorigenic tissue or by using tumor-specific promoters to control essential early viral genes. However, various preclinical and clinical studies with oncolytics suggest that, though tumor specificity and replication are achieved, viral replication alone may not be sufficient to inhibit tumor growth. Also, several reports have indicated that oncolytics expressing additional therapeutic genes may also improve anti-tumor effects. Here we describe the construction and functional characterization of a green fluorescence protein (GFP)-expressing oncolytic adenovirus designated Ad/hTC-GFP-E1, whose transgene, GFP, and viral E1A gene are both under the control of a synthetic promoter (hTC) consisting of fusion sequences from the human telomorase reverse transcriptase (hTERT) promoter and minimal cytomegalovirus early promoter (CMV). hTC is used twice to express viral genes and transgenes separately, at high levels and in a tumor-specific manner, providing tumor restricted viral replication and additional effects mediated by the transgene of choice. Our virus' tumor specificity has been demonstrated by Western blot, fluorescence-activated cell sorting analysis, crystal violet staining, and cell viability assays. In addition, our virus has been shown to replicate and cause the eventual lysis of sensitive cell lines at multiplicities of infection (MOIs) as low as 10 viral particles per cell. In construction, no obvious cytotoxic effect was observed in normal human fibroblasts even at MOIs over 2000. The oncolytic vector, with the inclusion of an hTC-driven fluorescent reporter, GFP, can also be readily visualized in vitro and in vivo, in correlation with viral replication. Our results show that construction of an hTERT-specific, transgene-expressing oncolytic adenovirus is practical and useful for cancer therapy.
Variations in Small-intestinal Villous Shape and Mucosal Dynamics
Authors: B. Creamer
Journal: BMJ (1964)

Nephritis-Summerly and Copeman BRIT 1371 abnormal in individuals with an inborn tendency to psoriasis, thus after an interval of 10 to 15 days producing the lesions of psoriasis (Whyte and Baughman, 1964).An antigen-antibody reaction centred on the dermal capillaries, similar to that which occurs in the glomerular capillaries in acute nephritis, seems unlikely, as fluorescent antibody studies carried out on psoriatic skin have been negative (Raskin, 1964).Pyoderma in patients with seborrhoeic eczema is a very common complication; it is much rarer in atopic eczema, yet 4 out of 492 patients suffering from atopic eczema were found to have glomerulonephritis on presentation (Roth and Kierland, 1964).Impetigo has been reported as a common precursor of glomerulonephritis in the U.S.A. (Blumberg and Feldman, 1962).This could be true in this country: over the past two years in our department half the cultures from 24 patients with impetigo grew beta-haemolytic streptococci.It is interesting that two of our patients (Cases 3 and 6) had acute rheumatism in adolescence-a further manifestation of their streptococcal hypersensitivity. SummaryNephritis may occur with common skin diseases.Examples of various types of nephritis associated with anaphylactoid purpura, erythema muItfwrme, erythema nodosum, acute guttate psoriasis, and infected eczema are given.We are grateful for the help of Drs.H.
Patterns of Red Marrow in the Adult Femur
Authors: Suk Chul Kim, Borys R. Krynyckyi, Josef Machac, Chun K. Kim
Journal: Clinical Nuclear Medicine (2006)

Purpose: Conversion of red marrow (RM) to fatty marrow in the skeleton of the lower extremities begins at the distal end, ie, feet, and progresses proximally with distal bone marrow (ie, tibia) being converted more rapidly than proximal bone marrow (ie, femur). However, in an individual long bone, conversion begins in the diaphysis and progresses both distally and proximally (more rapidly toward the distal side). In a normal adult’s femur, RM is present in the proximal one third or less. Reconversion of fatty marrow to RM is reported to occur in the reverse order of conversion. We assessed the frequency of various patterns of RM in the adult femur on In-111 leukocyte scans for a better understanding of the bone marrow regeneration process in individual long bones. Methods: The patterns of marrow activity in the femur shown on In-111 leukocyte scans performed in 354 adults were divided into a) RM limited to the proximal one third or less, b) to the proximal two thirds, c) to the proximal one third and distal one third with no activity in the middle shaft, and d) in the entire femur. Results: There were 207 patients with pattern A, 91 pattern B, 14 pattern C, and 42 pattern D. Conclusions: A considerably higher number of adults showed pattern B than pattern C. This suggests that regeneration of diaphyseal marrow precedes that of the distal marrow in an individual long bone or possibly that conversion of the latter precedes the former, which is different from that proposed in the literature.
Pacemaker selectivity: influence on rabbit atria of ionic environment and of alinidine, a possible anion antagonist
Authors: J S MILLAR, E M V. WILLIAMS
Journal: Cardiovascular Research (1981)

Alinidine, a new compound which reduces heart rate in man and animals, has a selective action on the sinus node. The dose-response relation between alinidine and frequency is not altered by atropine, and alinidine does not block the positive chronotropic action of isoprenaline. Alinidine has no negative inotropic action and has no effect on the linear relation between extracellular Ca and force of myocardial contraction. Alinidine did not alter the slope of the relation between frequency and external calcium concentration. Intracellular recordings showed that alinidine had no effect on the maximum rate of depolarisation or overshoot potential of rabbit atrial muscle, nor was conduction velocity, electrical threshold or maximum follow frequency affected. It was concluded that alinidine did not restrict current through fast inward channels. Alinidine did not increase resting potential or accelerate repolarisation, suggesting that potassium conductance was not increased. The effect of alinidine on frequency was not increased in 14 mmol . litre-1 KCl, or decreased in 2.24 mmol . litre-1 KCl, suggesting that the attachment of alinidine to receptors was not voltage-dependent. Spontaneous frequency was higher when NaCl was replaced by NaBr, and the bradycardic effect of alinidine was increased. Conversely, frequency was lower in NaCH3SO4 and the slope of the dose-response curve decreased. Intracellular recordings from sinus node cells showed that alinidine decreased the slope of the slow diastolic depolarisation and increased action potential duration, without altering the overshoot, the maximum diastolic potential, or the "take-off" potential. A possible explanation for these results is that alinidine restricts current through anion-selective channels. If so, the high potency of alinidine suggests that anionic current normally carries a substantial fraction of the current causing slow diastolic depolarisation.
THE ACTION OF ALCOHOL ON THE NORMAL INTACT UNANESTHETIZED ANIMAL
Authors: CLYDE BROOKS
Journal: JAMA (1910)

INTRODUCTION  Heretofore, on account of the objectionable methods employed, so far as I know no adequate direct observations have been recorded on the action of alcohol on the general blood-pressure of the intact animal. One objectionable feature is that these methods have as a rule involved the employment of a general anesthetic, such as chloroform or ether; and it is not easy to distinguish the normal action of alcohol when administered to an animal already far under the influence of a very closely related drug of the same group. For example, how could one distinguish the normal action of alcohol on the general blood-pressure of an animal when its vasomotor reflexes were already greatly depressed by ether or chloroform? One of the means employed to avoid the use of anesthetics is to remove the cerebral hemispheres. 1 But this is a poor makeshift, for an animal with its cerebral hemispheres mutilated
Immunologic Thrombocytopenic Purpura after Heterosexual Transmission of Human Immunodeficiency Virus (HIV)
Authors: Simon Karpatkin
Journal: Annals of Internal Medicine (1988)

We report four cases of immunologic thrombocytopenic purpura related to human immunodeficiency virus (HIV) transmitted through heterosexual contact in persons who were not homosexual, addicted to intravenous narcotic drugs, or hemophilic. Each transmission occurred in a different setting. A 23-year-old white woman had immunologic thrombocytopenic purpura in July 1985, with a platelet count of 11 X 10(9)/L. In January 1987, she had prominent submandibular and posterior cervical adenopathy. A careful social-sexual history revealed several sexual contacts with a male narcotic addict before July 1985. A 27-year-old heterosexual white man had a platelet count of 8 X 10(9)/L in December 1986. A social-sexual history revealed that his fiancée had been an intravenous narcotic addict 6 years ago. A 64-year-old white woman had a platelet count of 75 X 10(9)/L in May 1986, approximately 2 years after she had resumed having sexual intercourse with her husband who had had a triple coronary bypass in October 1983. The husband had received HIV-seropositive blood. A 42-year-old white man had a platelet count of 45 X 10(9)/L, which was associated with a cutaneous eruption refractory to antibiotics and antifungal agents. He had had sexual contacts with several women, who, to the best of his knowledge, were neither prostitutes nor intravenous narcotic addicts. He denied homosexuality or drug abuse. All four patients were HIV-seropositive and had circulating immune complexes and platelet-associated IgG, C3C4, and IgM values that were considerably higher than those usually measured in patients with classic autoimmune thrombocytopenia, averaging 2.4-, 2.2-, 6.5- and 5.2-fold higher, respectively. Thus, HIV-related immunologic thrombocytopenic purpura can be heterosexually spread and should become part of the differential diagnosis of unexplained thrombocytopenia. Obtaining a careful social-sexual history is mandatory in such patients.