tbuckley/cabot-search huggingface dataset:
Crucial residues in the carboxy-terminal end of C1 inhibitor revealed by pathogenic mutants impaired in secretion or function.
Authors: E Verpy, E Couture-Tosi, E Eldering, M Lopez-Trascasa, P Späth, T Meo, M Tosi
Journal: Journal of Clinical Investigation (1995)

The last exon of the C1-1NH gene was screened for point mutations in 36 unrelated hereditary angioedema patients. Mutations were found in eight patients, predicting changes in the short COOH-terminal region which anchors the reactive site loop on its COOH-terminal side. The effects of each of these mutations were examined in transiently transfected Cos-7 cells. Complete intracellular retention or degradation was observed with substitutions in the COOH-terminal strands 4B or 5B: Leu459-->Pro, Leu459-->Arg, and Pro467-->Arg were all blocked at early stages of intracellular transport, but differences in the immunofluorescence patterns indicated that a significant fraction of the Leu459-->Pro and of the Pro467-->Arg proteins reached a compartment distinct from the endoplasmic reticulum. In line with previous findings with alpha 1-antitrypsin, chain termination within strand 5B resulted in rapid degradation. Mutant Val451-->Met, in strand 1C, and mutant Pro476-->Ser, replacing the invariant proline near the COOH terminus, yielded reduced secretion, but these extracellular proteins were unable to bind the target protease C1s. Presence of low levels of both dysfunctional proteins in patient plasmas defies the conventional classification of C1 inhibitor deficiencies as type I or type II. These data point to a key role of certain residues in the conserved COOH-terminal region of serpins in determining the protein foldings compatible with transport and proper exposure of the reactive site loop.
Suicide Over the Life Cycle: Risk Factors, Assessment, and Treatment of Suicidal Patients
Authors: L. D. Hankoff
Journal: JAMA (1991)

While there is no dearth of new books on suicide, the present volume is outstanding as a textbook for its rigor and comprehensiveness. As a health care issue, suicide remains, along with other behaviorally based health care issues, largely unaltered by the remarkable advances in the area of scientific psychiatry and medicine. Suicide rates persist, reflective of forces outside direct medical care and unaltered by the enormous attention given the subject.  The very title of the present volume moves squarely to the basic issue, often overlooked, that the problem of suicide comprises not one but many human presentations. The manifestations of suicidal behavior, both fatal and attempted, may represent quite different phenomena and clinical challenges over the life cycle. Suicide among adolescents differs markedly from suicide among the elderly. Similarly, suicide in different subpopulations reflects different factors and descriptive elements.  Blumenthal and Kupfer have provided a volume that goes beyond
IMPROVED METHODS FOR THE GUAIAC TEST FOR BLOOD AND THE OXIDATION TEST FOR INDICAN.
Authors: JAMES W. HOLLAND
Journal: JAMA (1907)

The usual method for the guaiac test calls for an old sample of turpentine which has dissolved active oxygen from the air, or in lieu of it a fresh bottle of hydrogen dioxid. The turpentine of ripe age is not always at hand and, like the hydrogen dioxid that has been used through the summer, is of uncertain oxidizing power. An oxidizer of constant strength in any climate is much to be desired. In the usual process liquid reagents are employed in the test tube, which means a larger volume of the blood material than can always be obtained and a response not sensitive enough for small quantities. Sometimes a few threads of blood-stained linen are all that can be had. <h3>THE MODIFIED GUAIAC TEST.</h3> To meet this difficulty the following modification is proposed: The oxidizing agent is sodium perborate as made by Schering from sodium dioxid and boric acid.
Effect of the Medicare Part D Coverage Gap on Medication Use Among Patients With Hypertension and Hyperlipidemia
Authors: Pengxiang Li, Sean McElligott, Henry Bergquist, J. Sanford Schwartz, Jalpa A. Doshi
Journal: Annals of Internal Medicine (2012)

Background: Prior studies of the Medicare Part D coverage gap are limited in generalizability and scope. Objective: To determine the effect of the coverage gap on drugs used for asymptomatic (antihypertensive and lipid-lowering drugs) and symptomatic (pain relievers, acid suppressants, and antidepressants) conditions in elderly patients with hypertension and hyperlipidemia. Design: Quasi-experimental study using pre–post design and contemporaneous control group. Setting: Medicare claims files from 2005 and 2006 for 5% random sample of Medicare beneficiaries. Patients: Part D plan enrollees with hypertension or hyperlipidemia aged 65 years or older who had no coverage, generic-only coverage, or both brand-name and generic coverage during the gap in 2006. Patients who were fully eligible for the low-income subsidy served as the control group. Measurements: Monthly 30-day supply prescriptions available, medication adherence, and continuous medication gaps of 30 days or more for antihypertensive or lipid-lowering drugs; monthly 30-day supply prescriptions available for pain relievers, acid suppressants, or antidepressants before and after coverage gap entry. Results: Patients with no gap coverage had a decrease in monthly antihypertensive and lipid-lowering drug prescriptions during the coverage gap. Nonadherence also increased in this group (antihypertensives: odds ratio [OR], 1.60 [95% CI, 1.50 to 1.71]; lipid-lowering drugs: OR, 1.59 [CI, 1.50 to 1.68]). The proportion of patients with no gap coverage who had continuous medication gaps in lipid-lowering medication use and antihypertensive use increased by an absolute 7.3% (OR, 1.38 [CI, 1.29 to 1.46]) and 3.2% (OR, 1.35 [CI, 1.25 to 1.45]), respectively, because of the coverage gap. Decreases in use were smaller for pain relievers and antidepressants and larger for acid suppressants in patients with no gap coverage. Patients with generic-only coverage had decreased use of cardiovascular medications but no change in use of drugs for symptomatic conditions. No measures changed in the brand-name and generic coverage groups. Results of sensitivity analyses were consistent with the main findings. Limitation: Because this study was nonrandomized, unobserved differences may still exist between study groups. Conclusion: The Part D coverage gap was associated with decreased use of medications for hypertension and hyperlipidemia in patients with no gap coverage and generic-only gap coverage. The proposed phasing out of the gap by 2020 will benefit such patients; however, use of low-value medications may also increase. Primary Funding Source: Penn–Pfizer Alliance and American Heart Association.
Polyion complex micelle MRI contrast agents from poly(ethylene glycol)-b-poly(l-lysine) block copolymers having Gd-DOTA; preparations and their control of T1-relaxivities and blood circulation characteristics
Authors: Kouichi Shiraishi, Kumi Kawano, Yoshie Maitani, Masayuki Yokoyama
Journal: Journal of Controlled Release (2010)
Underprivileged areas: validation and distribution of scores.
Authors: B Jarman
Journal: BMJ (1984)

Underprivileged areas were identified by weighting several census variables that relate to social conditions, by using weights determined by means of a questionnaire sent to one in 10 of the general practitioners in the United Kingdom. The weighted variables were added (after statistical manipulation) to give a score for each of the 9265 electoral wards in England and Wales. Blank ward maps were sent to general practitioners in five family practitioner committee areas and they were asked to shade the wards according to the degree to which the population increased their workload or the pressure on their services. Maps of these same areas were then prepared by using the calculated scores with the cut off points between the worst, the intermediate, and the best areas as on those used by the general practitioners. The two sets of maps were then compared to determine how well the maps that were based on scores agreed with the general practitioners9 maps showing their assessment of the variation of workload in their areas. Overall, 6.3% of the wards differed in shading in any way between the two sets of maps. In the three areas where the general practitioners shaded complete wards and did not report having difficulties with shading only 1.2% of the wards differed. It may be possible to use these "underprivileged area" scores to indicate where problems occur for general practitioners and to extend this work to other primary health care workers.
Cancer Incidence among Pesticide Applicators Exposed to Dicamba in the Agricultural Health Study
Authors: Claudine Samanic, Jennifer Rusiecki, Mustafa Dosemeci, Lifang Hou, Jane A. Hoppin, Dale P. Sandler, Jay Lubin, Aaron Blair, Michael C.R. Alavanja
Journal: Environmental Health Perspectives (2006)

Dicamba is an herbicide commonly applied to crops in the United States and abroad. We evaluated cancer incidence among pesticide applicators exposed to dicamba in the Agricultural Health Study, a prospective cohort of licensed pesticide applicators in North Carolina and Iowa.
Geographic Differences in US Health Care Spending
Authors: Michael Kitchell
Journal: JAMA (2014)

In their Viewpoint regarding the Institute of Medicine (IOM) report on geographic variation in health care spending, Drs Newhouse and Garber1 indicated the spending data were adjusted for geographically different input prices.

Use of a flawed input price–adjustment method leaves many of the IOM report’s conclusions in doubt. The input price adjustment did not use the actual dollars spent on physician work but used geographic practice cost index (GPCI) adjusters to change the spending figures to reflect local differences in input price.2
Tumors of the Head and Neck: Clinical and Pathological Considerations
Authors: John E. Hoopes
Journal: JAMA (1974)

Students of head and neck surgery must add this volume to their personal libraries. Dr. Batsakis is to be commended for providing a single reference source containing virtually every lesion—benign, malignant, and nonneoplastic—that might be encountered superior to the clavicles. With the exception of odontogenic tumors and cysts, which had purposely been omitted, the text provides comprehensive information concerning congenital and acquired lesions, both neoplastic and nonneoplastic. Special mention must be awarded to the section dealing with metastatic lesions to and from the head and neck, to the excellent review of the occult primary with cervical metastasis, and to the section dealing with fibrous lesions of the head and neck. The pathologic discussions provide excellent and thorough presentations of histogenesis, classification, and clinical pathological correlations. The clinical material is excellent in terms of diagnosis, natural history, and survival statistics. Treatment of the various lesions receives scant attention; however, "it is
S1-3: Long-Term Survival Outcomes among Postmenopausal Women with Hormone Receptor-Positive Early Breast Cancer Receiving Adjuvant Letrozole and Zoledronic Acid: 5-Year Follow-Up of ZO-FAST.
Authors: R de Boer, N Bundred, H Eidtmann, P Neven, G von Minckwitz, N Martin, A Modi, R Coleman
Journal: Cancer Research (2011)

Abstract Introduction: Recent clinical trials suggest potential anticancer activity for bisphosphonates combined with adjuvant endocrine therapy in patients with hormone receptor-positive (HR+) early breast cancer (EBC). Data from the interim analysis of AZURE suggest that the benefits of adding zoledronic acid (ZOL) may be greatest in patients with low estrogen levels (Coleman RE, et al. SABCS 2010). In ZO-FAST, we have previously demonstrated that adding ZOL to adjuvant therapy significantly improved bone mineral density (BMD) and prolonged disease-free survival (DFS) vs delayed ZOL (de Boer R, et al. SABCS 2010). We report here the effect of time since menopause at breast cancer diagnosis (ie, baseline menopausal status) on DFS benefits with ZOL. Methods: Postmenopausal women with HR+ EBC receiving letrozole (LET; 2.5 mg qd x 5 yr) with a BMD T-score ≥-2 (N=1065) were randomized to ZOL (4 mg q6mo): immediate (IMZOL) or delayed (DZOL; initiated for postbaseline T-score &amp;lt;-2 or nontraumatic/asymptomatic fracture). Patients were followed for disease recurrence and overall survival (OS) for 5 years. Patients were eligible for the study if they had established menopause at the time of diagnosis, or if they became menopausal because of chemotherapy or ovarian suppression (ie, recently postmenopausal). The effect of baseline menopausal status on DFS was examined in Cox regression analyses. Results: At 60 months’ follow-up in the overall population (N=1065), IMZOL significantly reduced the risk of a DFS event by 34% vs DZOL (hazard ratio [HR]=0.66; 95% confidence interval [CI], 0.44−0.97; P=.034). In exploratory analyses of women who were postmenopausal for &amp;gt;5 years or &amp;gt;60 years old at study entry (n=670), IMZOL improved DFS (HR=0.63; 95% CI, 0.39−1.01; P=.052) and significantly prolonged OS (HR=0.50; 95% CI, 0.27−0.92; P=.022) vs DZOL. Additional subgroup analyses including patterns of breast cancer recurrence will be presented. During 5 years of treatment, osteonecrosis of the jaw (ONJ) was reported in 4/669 patients (0.6%) who received ZOL, and there was no increase in renal adverse events (AEs) in the ZOL-treated patients. Overall, AEs were consistent with the known safety profiles of both study drugs. Conclusions: Long-term follow-up in ZO-FAST confirms the overall survival benefits of adding ZOL (4 mg q6mo) to adjuvant LET therapy for EBC. However, subset analyses suggest that women with established postmenopausal status may benefit from ZOL therapy more than others. These results are consistent with observations in the AZURE trial, and support potentially greater ZOL benefits in a low-estrogen environment. Additional studies are needed to fully define the patient populations most likely to benefit from adjuvant ZOL in this setting. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr S1-3.
FDG Uptake in a Catheter-Related Thrombus Simulating Relapse of Lymphoma
Authors: Anna-Karin Si??steen, Fredrik Celsing, Hans Jacobsson
Journal: Clinical Nuclear Medicine (2005)

FDG-PET imaging was performed because of suspected recurrence of lymphoma of the chest. There was an area of increased activity posterior to the left sternoclavicular joint, suspected of being a relapse. Workup showed a thrombus at the tip of a central venous line corresponding to the FDG uptake. This is explained by the inflammatory process involving and surrounding chronic thrombus. Focal activity in relation to the tip of a venous catheter is very likely to have a benign etiology. It is important to recognize this not to overdiagnose a malignancy. For a correct interpretation, it is necessary to know the patient's history and having access to current radiologic examinations.
Temporal Changes in Interpapillary Muscle Dynamics as an Active Indicator of Mitral Valve and Left Ventricular Interaction in Ischemic Mitral Regurgitation
Authors: Kanika Kalra, Qian Wang, Bryant V. McIver, Weiwei Shi, Robert A. Guyton, Wei Sun, Eric L. Sarin, Vinod H. Thourani, Muralidhar Padala
Journal: Journal of the American College of Cardiology (2014)
Spinal Phlebography: Lumbar and Cervical Techniques
Authors: M. I. V. Jayson
Journal: Annals of the Rheumatic Diseases (1980)

Book reviews followed by chapters on the examination of individual joints, including the cricoarytenoid joint.At the beginning of each chapter there is a valuable section on essential anatomy followed by sections on inspection, palpation, movement and range of motion, muscle testing, and finally any special tests, The British reader might have wished for a wider discussion on the assessment of disease activity and spinal movement and there is no mention of the Richie index.This book should be read by all rheuma- tologists in training and it should be available for reference in every department.1. D. L. BREWIS
Abstract 3266: Interaction of MCM7 and RACK1 for activation of MCM7 and cell growth
Authors: Jian-Hua Luo, Xi-Yue Zhang, Yan Ping Yu
Journal: Cancer Research (2012)

Abstract MCM7 is one of the pivotal DNA replication licensing factors in controlling DNA synthesis and cell entry into S phase. Its expression and DNA copy number are some of the most predictive factors for the growth and behavior of human malignancies. In this study, we identified that MCM7 interacts with receptor for activated protein kinase C 1 (RACK1), a protein kinase C (PKC) adaptor in vivo and in vitro. The RACK1 binding motif in MCM7 is located at the amino acid 221-248. Knocking down of RACK1 significantly reduced MCM7 chromatin association, DNA synthesis and cell cycle entry into S phase. Activation of PKC by 12-O-tetradecanoylphorbol-13-acetate dramatically decreased MCM7 DNA replication licensing and induced cell growth arrest. Activation of PKC induced redistribution of RACK1 from nucleus to cytoplasm, and decreased RACK1-chromatin association. MCM7 mutant that does not bind RACK1 has no DNA replication licensing nor oncogenic transformation activity. As a result, this study demonstrates a novel signaling mechanism that critically controls DNA synthesis and cell cycle progression. 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 3266. doi:1538-7445.AM2012-3266
Book Review Type 2 Diabetes, Pre-Diabetes, and the Metabolic Syndrome: The Primary Care Guide to Diagnosis and Management (Current Clinical Practice.) By Ronald A. Codario. 247 pp. Totowa, N.J., Humana Press, 2005. $89.50. 1-58829-471-4
Authors: David R. Hadden
Journal: New England Journal of Medicine (2006)
THROMBO-ANGIITIS OBLITERANS
Authors: C. Dickson
Journal: BMJ (1925)

r~~~~~~~~~~~~~~~~(1;m~I MEDICAL JOUMEAS The effect was remarkable.I was called away, but returned in three hours to find the clhild's appearance woniderfully improved.A feed had been taken, anid the depressioni of the fonitanelle, which had been very marked, had vanished, and the patient's appearance was nio loniger that of a dyinjg clhild.A second transfusion was performed a few lhours later in the hiope of intensifying this evidenitly beneficial effect; 25 c.cm. of citrated blood were easily introduced, usinig the samne syrinige and needle all the time, and necessitating three introductions of tlle ieedle inlto the mothier's veini and three inito the child's vein.Unfortunately twenty-four hours later the chlild went into con- vulsionis and died, but I do niot associate this with the transfusion in any way, for there were maniy pus cells in the urine, and there was probably a general blood infection.There was no difficulty in passing the needle into the same wound in each veiin each time, and tllere was not the slightest reflux of blood alonigside the nieedle from the baby's veini; ior, wlhen the nieedle was removed, was there aniy escape of blood so lonig as the peripheral enid of tlle vein was kept raised by the aneurysm needle.Giving anitimony intravenously in a stout subject with small veins whein dissection was necessary I lhave founid such reflux alonigside the needle troublesome, but blood is a more viscid flutid.Assumning the total blood weight to be one-thirteentlh the body weiglht, it seemed inadvisable to introduce more than 25 c.cm. of blood, and this could easily have been donie liad it beeni desirable.Certaini poinlts of detail perhaps call for comiiment.The
Book Review Color Atlas of Hematological Cytology Third edition. By F.G.J. Hayhoe and R.J. Flemans. 384 pp., illustrated. St. Louis, Mosby-Year Book, 1992. $125. 0-8151-4218-8 Blood: Atlas and Sourcebook of Hematology Second edition. By Carola T. Kapff and James H. Jandl. 158 pp., illustrated. Boston, Little, Brown, 1991. $95. 0-316-48274-9
Authors: W.J. Mitus
Journal: New England Journal of Medicine (1993)
Using the Nicotine Patch to Stop Smoking
Authors: William L. Toffler
Journal: JAMA (1995)

<h3>To the Editor.</h3> —We read with interest the meta-analysis of nicotine patch studies by Dr Fiore and colleagues.<sup>1</sup>Their article is a major contribution to the literature and provides important information about several issues regarding the use of nicotine patches. However, we are concerned with their suggestion that "the nicotine patch might be offered first with minimal assistance" and, if this failed, move on to using the patch with an "intermediate-intensity adjuvant," such as support and followup provided via telephone or using the approach detailed in the National Cancer Institute's manual for physicians.<sup>2</sup>Many readers may conclude that the patch is effective when used alone. We believe that such a conclusion is premature and is not adequately supported by available research. At a minimum, all of the studies analyzed by the authors provided instructions on use of the patch, some brief advice, and at least several follow-up contacts.
FEDERAL CAUSTIC POISON LAW
Authors: Chevalier Jackson
Journal: JAMA (1952)

To the Editor:  —It seems to me that the altruistic work of the American Medical Association that resulted in the extremely successful, lifesaving piece of public health legislation known as the Federal Caustic Poison Law is of such general interest as to justify publication of the final report of the Committee on Lye Legislation. This report, read at the June, 1952, meeting of the Section on Laryngology, Otology and Rhinology, follows.  As you all know, the Federal Caustic Poison Law, with whose enactment your Committee on Lye Legislation was concerned, was enacted in 1927. During the 25 years that have elapsed since that time, your Committee has been observing the working of the Law to determine whether or not any supplementary legislation could increase its protective efficiency.  After the enactment of the Federal Caustic Poison Law its enforcement was assigned to the Department of Agriculture. The Secretary of Agriculture, the
1217 MECHANISM OF HCV REPLICÓN RESISTANCE TO PSI-352938, A CYCLIC MONOPHOSPHATE PRODRUG OF 2'-α-F-2'-β-C-METHYLGUANOSINE
Authors: A.M. Lam, C. Espíritu, S. Bansal, H.M. Micolochick Steuer, V. Zennou, M.J. Otto, P.A. Furman
Journal: Journal of Hepatology (2011)
Internal redistribution of tissue protein synthesis in uremia
Authors: Leroy Shear
Journal: Journal of Clinical Investigation (1969)

Tissue composition and in vivo tissue protein synthesis were altered by acute uremia, induced in rats by bilateral nephrectomy. Net protein synthesis (anabolism minus catabolism) was increased in liver and heart and decreased in skeletal muscle, as judged from changes in total organ weight, ratios of protein: DNA and RNA: DNA, and leucine-(14)C incorporation into trichloroacetic acid (TCA)-insoluble, nucleic acid-free material. Concentration of free lysine, a major constituent of histones and ribonucleoproteins, also was increased in liver and decreased in skeletal muscle, a finding suggesting lysine shifted from muscle to liver in association with the changes in protein synthesis. Acute uremia also altered tissue levels of other amino acids. Hepatic concentrations and liver:blood concentration ratios tended to be increased for the essential, but not for the nonessential amino acids. Moreover, the phenylalanine:tyrosine concentration ratio, which reflects activity of the enzyme phenylalanine hydroxylase, was increased in blood, muscle, and liver. These findings indicate uremia selectively alters tissue composition and protein synthesis in different organs and may modify intermediary metabolism of some individual amino acids.