tbuckley/cabot-search huggingface dataset:
Multiple tissues express alpha 1-antitrypsin in transgenic mice and man.
Authors: J A Carlson, B B Rogers, R N Sifers, H K Hawkins, M J Finegold, S L Woo
Journal: Journal of Clinical Investigation (1988)

Hepatocytes are considered to be the predominant source of alpha 1-antitrypsin (AAT), the major antiprotease in human plasma. The development of emphysema in the hereditary PiZ AAT deficiency state suggests that inhibition of leukocyte elastase in the lung is a major function of this protein. In addition, patients with AAT deficiency are at increased risk for developing cholestasis in infancy and chronic liver disease as adults. The mechanism for hepatic cell injury, however, is not understood. Transgenic mice that express the normal human AAT gene demonstrate abundant AAT in hepatocytes and specific cell types of numerous nonhepatic tissues. Immunoperoxidase techniques have previously disclosed AAT in many of the cell types seen in transgenic mice; however, the issue of local synthesis vs. endocytosis in these cell types has remained unresolved. In this study, AAT mRNA was seen in a variety of tissues in the transgenic mouse. Immunoelectron microscopy of renal tubular and small intestinal epithelial cells in the transgenic mice demonstrated AAT within the cisternae of the rough endoplasmic reticulum, as in hepatocytes. These findings support the possibility of local synthesis in the various cell types. The results suggest that in addition to maintaining tissue integrity in the lung, the protease/antiprotease balance may have physiological functions in other organs as well.
Drug Concentrations and Overdosage
Authors: Stanton G. Axline, Harold J. Simon
Journal: JAMA (1964)

<h3>To the Editor:—</h3> Studies on the clinical pharmacology of drugs in newborn infants have uncovered a problem of overdosage which may be more common than is generally appreciated. Several medicaments are available only in a limited number of highly concentrated formulations. The requirements of premature and full-term newborn infants for very small total dosages necessitate very careful measurement of minute quantities of drug. Overdosage can easily occur. Specifically, kanamycin sulfate is available in only two formulations for injection, containing, respectively, 250 and 333 mg/ml. The dosage of this agent for newborn infants is approximately 8 mg per kilogram of body weight every 12 hours. The injection mass for a premature infant weighing 1 kg (2.204 lb) should therefore consist of 0.024 ml of the 333 mg/ml formulation, or 0.032 ml of the 250 mg/ml formulation. Clearly, these quantities are impossible to measure accurately in a syringe unless a prior dilution
Electrophoretic Method for Characterizing Thyroid Function
Authors: Sheldon Berger, M. S. Goldstein, Boyd E. Metzger
Journal: New England Journal of Medicine (1962)

VIRTUALLY all the thyroxine (T4) in plasma circulates in association with various carrier proteins.1 2 3 4 The electrophoretic identity of these proteins depends upon experimental conditions, however, and herein lay the basis of a controversy that has surrounded efforts to characterize the "physiologic" carrier proteins. An inter-alpha globulin (the thyroxine-binding globulin, or TBG) is generally conceded to be the major thyroxine carrier; the albumin fraction shows a lesser but consistent role in thyroxine transport. The demonstration of a prealbumin carrier by Ingbar5 (thyroxine-binding prealbumin, or TBPA) has generated some discussion3 , 6 , 7 since this fraction shows no affinity for thyroxine when a . . .
The AMA and the Physicians Committee for Responsible Medicine
Authors: Neal D. Barnard
Journal: JAMA (1992)

<h3>To the Editor.</h3> —Let me correct a statement in the December 25,1991, issue ofTHE Journal<sup>1</sup>in which Dr Loeb stated that the Physicians Committee for Responsible Medicine (PCRM) had been "officially censured." Censure is used by the American Medical Association (AMA) for specific purposes, and PCRM has never been the subject of any such proceeding. The AMA and PCRM have had strong differences. In 1989, the AMA released its Animal Research Action Plan and has devoted substantial expenditures to pushing animal experimentation. Because PCRM has successfully promoted inquiry into and alternatives to animal experimentation, the AMA is increasingly sniping at PCRM. In 1990, the AMA House of Delegates considered a resolution brought by the California delegation that objected to PCRM for "implying that physicians who support the use of animals in biomedical research are irresponsible, for misrepresenting the critical role animals play in research and teaching, and for
THE CLINICAL RECOGNITION OF MALIGNANCY IN TUMORS.Read in the Section on Surgery and Anatomy, at the Forty-fifth Annual Meeting of the American Medical Association, held at San Francisco, June 5-8,1894.
Authors: CHARLES A. WHEATON
Journal: JAMA (1894)

This subject has invited the attention of some of the brightest minds of our generation. To attempt a delineation of the specific outlines of a clinical picture of malignant disease is an undertaking of no small dimensions. It is usually easy for the thoroughly trained student of pathology to distinguish between benignancy and malignancy when he has sections of each under his microscope; but it is often a very different matter when the cases are presented clinically, and he has to straighten out the tangled threads of his clinical story that he may advise and act judiciously. The microscopist may be able to tell us all about the histologie character of cancer in its various forms, but it is primarily the surgeon's function to formulate his plan of defense and attack, on gross appearances and the clinical history. Prof. Daniel Lewis, of New York, in his little monograph (edition of
A Case of Dracontiasis
Authors: W. L. M. Perry
Journal: BMJ (1948)

BDICOURNA 107 polycystic spleen is occasionally found post mortem.The solitary false cyst is probably the end-result of a haematoma.Case ReportA spinster aged 50 complained of vague abdominal pain and intermittent attacks of nausea and vomiting.During routine barium-meal examination a shadow was seen; no other
REPORT OF A CASE OF UNUSUAL TERTIARY MANIFESTATIONS.
Authors: G. HUDSON MAKUEN
Journal: JAMA (1901)

The patient, H. H., aged 22, had scarlet fever, followed by a severe attack of Bright's disease, at the age of 3 years. He made a speedy recovery, and was in good health up to September, 1899, when he contracted syphilis, while at school. The disease was recognized by his school physician, and for several months he was kept on the usual anti-syphilitic treatment. Upon his arrival home, however, in the summer of 1900, he decided not to reveal the fact of his infection, even to his family physician, and he gave up all medication. In August he enlisted in the war with Spain, and while in camp contracted intermittent fever. When he returned home in the autumn, he was much debilitated and had several paroxysms of what his family physician, in the absence of a history of specific disease, and, indeed, not suspecting it, on account of his long
Cerebral Venous Thrombosis: With Special Reference to Primary Aseptic Thrombosis
Authors: Martin R. Krigman
Journal: JAMA (1967)

The book is a welcome treatise, since in most texts the discussion of cerebral venous embryology, the histology and pathology, the clinical manifestations of cerebral venous thrombosis, and therapy is cursory.  The initial chapters are devoted to the embryology, anatomy, and histology of the cerebral venous system. A chapter on clinical manifestations of cerebral venous thrombosis emphasizes the complexity of this subject. It also provides an introduction to the 32 well-documented cases which form the substance of the book. These cases are divided into pediatric and adult examples; the clinical and pathological differences between the two groups warrant such a division. In addition, the series is sufficiently large to be further subdivided on the basis of chronicity. A critical analysis of the clinicopathological findings supplements the case reports. The last chapter, devoted to pathology, radiology, therapy, and prognosis of cerebral venous thrombosis, summarizes what has already been stated and presents
Comparison of Cortisone and Aspirin in Treatment of Juvenile Rheumatoid Arthritis
Authors: B. M. Ansell, E. G. L. Bywaters, I. C. Isdale
Journal: BMJ (1956)

These concerned 61 adult patients aged between 17 and 59 years admitted to six centres in England and Scotland.At the same time the committee started a similar trial in juvenile rheumatoid arthritis (Still's disease), which was defined for this purpose as beginning before the age of 16.Of the 25 patients taken into this trial, 22 came from this centre and 1 each from Edinburgh (Dr.Duthie), Sheffield (Dr.West), and Manchester (Professor Kellgren).They have been treated and followed along the same lines to one year from the start of treatment, at first in hospital and then as out-patients with cortisone (13 patients) or with aspirin (12 patients), their alloca- tion to one or other treatment being determined by a random order list held centrally.The criteria for admission were slightly less exclusive than for the adult trial; the disease had to be present for a period up to nine months, and three cases of less than three months' duration were included when the diagnosis was other- wise clear (one in the cortisone group and two in the
Effects of Iron Overload on Ascorbic Acid Metabolism
Authors: A. A. Wapnick, S. R. Lynch, P. Krawitz, H. C. Seftel, R. W. Charlton, T. H. Bothwell
Journal: BMJ (1968)

Studies of the ascorbic acid status in two subjects with idiopathic haemochromatosis and in 12 with transfusional siderosis showed that all had decreased levels of white cell ascorbic acid. The urinary excretion of ascorbic acid was also diminished in those subjects in whom such measurements were made. The administration of ascorbic acid was followed by only a small rise in the urinary ascorbic acid output, while the oxalic acid levels (measured in two subjects) showed a significant rise. These findings resemble those described in siderotic Bantu, and support the thesis that increased iron stores lead to irreversible oxidation of some of the available ascorbic acid.
Functional Aortic Stenosis
Authors: ANDREW G. MORROW, EUGENE BRAUNWALD
Journal: Circulation (1959)

When the clinical findings of aortic stenosis are present and a pressure gradient is demonstrated between the left ventricle and aorta, a discrete site of obstruction, generally amenable to surgical correction, has been assumed. The fallacy of this widely held concept is emphasized by the operative and hemodynamic findings in 3 patients described.
TREATMENT OF PERNICIOUS ANEMIA BY A SPECIAL DIET
Authors: C. Elders
Journal: JAMA (1926)

<h3>To the Editor:</h3> —In their important article "Treatment of Pernicious Anemia by a Special Diet" (The Journal, August 14), Minot and Murphy honor me by quoting one of my articles in relation to deficiency as a cause of pernicious anemia. The authors, however, misunderstood my work and this wants rectification. Though in the article to which they refer and in other publications I defended the view that pernicious anemia must be caused by deficiency, I never thought or wrote that I thought it was caused by lack of a single known or still unknown vitamin. Pernicious anemia is a complicated symptom complex and therefore it is, in my opinion, caused by a lack of different substances in the food, which are to be found in a diet rich in complete proteins (meat, milk, yellow of eggs) and rich in the known vitamins. This led me to treat pernicious anemia with
STUDIES ON THE SENSITIZATION OF ANIMALS WITH SIMPLE CHEMICAL COMPOUNDS. II
Authors: K. Landsteiner, John Jacobs
Journal: The Journal of Experimental Medicine (1936)

In continuation of previous work sensitization experiments have been made with various substances such as urushiol, benzyl chlorides, and acyl chlorides. In the case of a series of substituted benzenes (Cl, NO2) a connection between sensitizing capacity and lability of the Cl or NO2 groups has been shown, indicating the formation of conjugated antigens in the animal. This led to the study of benzyl and acyl chlorides which, actually, were found to have sensitizing capacity. Most informative as to the relationship between reactions of the skin surface and anaphylaxis were experiments with acyl chlorides. Guinea pigs sensitized with p-chlorobenzoyl chloride showed, on the one hand, the usual surface lesions after application of the substance, and on the other typical anaphylactic shock following intravenous injection of a compound of p-chlorobenzoyl chloride and guinea pig serum; from which it may be inferred that the two types of allergic manifestation are closely related conditions.
SOME PROPERTIES OF AN ESTERASE DERIVED FROM PREPARATIONS OF THE FIRST COMPONENT OF COMPLEMENT
Authors: Oscar D. Ratnoff, Irwin H. Lepow
Journal: The Journal of Experimental Medicine (1957)

Studies on an esterase derived from partially purified preparations of the first component of complement are described. The esterase hydrolyzed certain synthetic amino acid esters, among which N-acetyl-L-tyrosine ethyl ester was most susceptible. This was hydrolyzed maximally between pH 7.5 and 8.2, and at 41 degrees C. The esterase could not be identified with other previously described hydrolytic enzymes. An esterase with similar properties could also be eluted from antigen-antibody aggregates which had been treated with serum. Human serum contained a heat-labile inhibitor of the esterase which could not be identified with any of the known components of complement. The esterase was also inhibited by certain reducing agents. The experiments described support the early hypothesis that complement exerts its action enzymatically, but the physiological role of the esterase derived from preparations of complement is not yet clear.
Adenosine modulates oesophageal sensorimotor function in humans
Authors: J. M. Remes-Troche, P. Chahal, R. Mudipalli, S. S. C. Rao
Journal: Gut (2008)

<h3>Background and aims:</h3> Adenosine mediates somatic and visceral pain, but its effects on gut visceral nociception are unknown. The aim of the present study was to test the hypothesis that adenosine alters oesophageal sensorimotor function. <h3>Methods:</h3> In a double-blind, randomised, placebo-controlled study, 14 healthy volunteers (M/F = 4/10) received either intravenous adenosine 100 μg/kg/min or placebo infusion. Prior to and during infusion, all subjects underwent stepwise graded oesophageal balloon distensions using impedance planimetry. Sensory responses and biomechanical properties were assessed and compared. <h3>Results:</h3> Adenosine significantly lowered thresholds for first perception (median (25th–75th), cm H<sub>2</sub>O; 10 (10–20) vs 30 (20–30), p = 0.007), discomfort (40 (30–40) vs 50 (50–60), p = 0.011) and pain (50 (40–60) vs 70 (60–70), p = 0.007) when compared with placebo. Also, the median threshold pressures required to induce first perception (p = 0.017), discomfort (p = 0.024) and pain (p = 0.026) were lower when compared with baseline. The cross-sectional area of the oesophagus increased (p = 0.032), and the circumferential wall tension/strain relationship shifted to the left (the wall became stiffer) (p = 0.043) after adenosine, when compared with baseline or placebo. <h3>Conclusions:</h3> Adenosine can induce visceral hyperalgesia and decrease oesophageal distensibility in humans. These evoked sensorimotor changes are similar to those described in patients with functional oesophageal (non-cardiac) chest pain. Thus, adenosine modulates oesophageal sensorimotor function and may play a role in the pathogenesis of functional chest pain.
Experienced Laparoscopic Surgeons are Automated to the “Fulcrum Effect”: An Ergonomic Demonstration
Authors: I. R. Crothers, A. G. Gallagher, N. McClure, D. T. D. James, J. McGuigan
Journal: Endoscopy (1999)

Minimal access surgery (MAS) is one of the most exciting advances in contemporary surgical practice. Since its introduction in gynaecology and general surgery it has developed rapidly in both application and complexity, with many forms of abdominal surgery now being performed by this route [1]. Indeed, laparoscopic cholecystectomy, considered an advanced surgical technique when introduced in 1987, now represents the "gold standard" treatment for the removal of the gallbladder, and is the surgical procedure most commonly used to investigate the benefits of MAS to the patient and health care system [2] [3].
Deceleration Trauma to the Heart and Great Vessels after Road-traffic Accidents
Authors: M. J. Goggin, F. D. Thompson, J. W. Jackson
Journal: BMJ (1970)

Four young men involved in high-speed car crashes developed cardiovascular trauma. Two patients had aortic aneurysms, one rupture of the mitral valve, and one ventricular septal defect; successful surgical correction was undertaken in all. The importance of considering the possibility of cardiovascular trauma in these circumstances is emphasized, and <i>x</i>-ray films (repeated if necessary) should be taken even when there are no external signs of trauma.
Adenosine triphosphatase, adenylate kinase, and collagen content of heart myofibrils in experimental aortic insufficiency
Authors: B. SWYNGHEDAUW, V. PIGUET, M. PRETESEILLE
Journal: Cardiovascular Research (1972)

In chronic aortic insufficiency the myofibrillar Ca2+ ATPase is low, whereas the ATPase of a non-purified actomyosin is normal. These results are essentially the same as those previously described for purified actomyosin. The lowered myofibrillar ATPase cannot be attributed to a dilution effect.
Medicine and MBAs
Authors: Aaron Levin
Journal: Annals of Internal Medicine (2000)

Currents20 June 2000Medicine and MBAsAaron LevinAaron LevinSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-132-12-200006200-00103 SectionsAboutFull Text ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Even before he took a new position as interim chairman in obstetrics and gynecology at the University of Maryland in Baltimore earlier this year, Hugh Mighty, MD, realized that “administration means more than signing checks” and enrolled in an executive master of business administration (MBA) program at a nearby college. He is not alone. Increasing numbers of physicians in the middle of their careers are examining the altered health care landscape and deciding—for personal or professional reasons—to become involved in both business and medicine.Some physicians believe that advanced training in management is necessary if their profession is to maintain ... Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByCritical Leadership and Management Skills for Pathology PracticeTraining in Laboratory Management and the MBA/MD in Laboratory MedicineOutcomes of a Program in Business Education for Physicians and Other Health Care Professionals 20 June 2000Volume 132, Issue 12Page: 1015KeywordsGraduate medical educationHealth careHealth maintenance organizationsMedical educationOutpatient clinicsPatientsPrevention, policy, and public healthQuality improvementResidencySoaps Issue Published: 20 June 2000 CopyrightCopyright © 2000 by American College of Physicians. All Rights Reserved.Loading ...
A Phase I First-in-Human Trial of Bardoxolone Methyl in Patients with Advanced Solid Tumors and Lymphomas
Authors: David S. Hong, Razelle Kurzrock, Jeffrey G. Supko, Xiaoying He, Aung Naing, Jennifer Wheler, Donald Lawrence, Joseph Paul Eder, Colin J. Meyer, Deborah A. Ferguson, James Mier, Marina Konopleva, Sergej Konoplev, Michael Andreeff, Donald Kufe, Hillard Lazarus, Geoffrey I. Shapiro, Bruce J. Dezube
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Bardoxolone methyl, a novel synthetic triterpenoid and antioxidant inflammation modulator, potently induces Nrf2 and inhibits NF-κB and Janus-activated kinase/STAT signaling. This first-in-human phase I clinical trial aimed to determine the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), and appropriate dose for phase II studies; characterize pharmacokinetic and pharmacodynamic parameters; and assess antitumor activity. Experimental Design: Bardoxolone methyl was administered orally once daily for 21 days of a 28-day cycle. An accelerated titration design was employed until a grade 2–related adverse event occurred. A standard 3 + 3 dose escalation was then employed until the MTD was reached. Single dose and steady-state plasma pharmacokinetics of the drug were characterized. Assessment of Nrf2 activation was examined in peripheral blood mononuclear cells (PBMC) by measuring NAD(P)H:quinone oxidoreductase (NQO1) mRNA levels. Immunohistochemical assessment of markers of inflammation, cell cycle, and apoptosis was carried out on tumor biopsies. Results: The DLTs were grade 3 reversible liver transaminase elevations. The MTD was established as 900 mg/d. A complete tumor response occurred in a mantle cell lymphoma patient, and a partial response was observed in an anaplastic thyroid carcinoma patient. NQO1 mRNA levels increased in PBMCs, and NF-κB and cyclin D1 levels decreased in tumor biopsies. Estimated glomerular filtration rate (eGFR) was also increased. Conclusions: Bardoxolone methyl was well tolerated with an MTD of 900 mg/d. The increase in eGFR suggests that bardoxolone methyl might be beneficial in chronic kidney disease. Objective tumor responses and pharmacodynamic effects were observed, supporting continued development of other synthetic triterpenoids in cancer. Clin Cancer Res; 18(12); 3396–406. ©2012 AACR.
Can we halt sudden cardiac death?
Authors: W. A. Check
Journal: JAMA (1981)

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