tbuckley/cabot-search huggingface dataset:
Release of carcinoembryonic antigen from human colon cancer cells by phosphatidylinositol-specific phospholipase C.
Authors: T L Sack, J R Gum, M G Low, Y S Kim
Journal: Journal of Clinical Investigation (1988)

Carcinoembryonic antigen (CEA) is released from colon cancer cells into the circulation where it is monitored clinically as an indicator of the recurrence or progression of cancer. We have studied the mechanism of CEA membrane attachment and release using the human colonic adenocarcinoma cell line LS-174T, specimens of human colon cancers, and serum from colon cancer patients. CEA release by cells in vitro and in vivo is associated with the conversion of CEA from a membrane-bound, hydrophobic molecule to a soluble, hydrophilic form with no apparent decrease in molecular mass. When LS-174T cell membranes were incubated with various buffers, proteases, and phospholipases, the only agents that released CEA and converted it to the hydrophilic form were preparations of phosphatidylinositol-specific phospholipase C (PI-PLC). Both [3H]ethanolamine and [3H]palmitate could be incorporated metabolically into CEA but only palmitate was released by treatment with PI-PLC, consistent with the presence of a glycosyl-phosphatidylinositol linkage. PI-PLC treatment also release significant quantities of CEA from living monolayers and from seven human colon cancer specimens. These experiments suggest that cellular CEA is anchored to membranes by a covalent linkage to a membrane phosphatidylinositol molecule, and that an endogenous phospholipase may be important for releasing CEA in vitro and in vivo.
X-Linked Thrombophilia with a Mutant Factor IX (Factor IX Padua)
Authors: Paolo Simioni, Daniela Tormene, Giulio Tognin, Sabrina Gavasso, Cristiana Bulato, Nicholas P. Iacobelli, Jonathan D. Finn, Luca Spiezia, Claudia Radu, Valder R. Arruda
Journal: New England Journal of Medicine (2009)

We report a case of juvenile thrombophilia associated with a substitution of leucine for arginine at position 338 (R338L) in the factor IX gene (factor IX-R338L). The level of the mutant factor IX protein in plasma was normal, but the clotting activity of factor IX from the proband was approximately eight times the normal level. In vitro, recombinant factor IX-R338L had a specific activity that was 5 to 10 times as high as that in the recombinant wild-type factor IX. The R338 substitution causes a gain-of-function mutation, resulting in factor IX that is hyperfunctional.
Internalization of constitutive desmogleins with the subsequent induction of desmoglein 2 in pemphigus lesions
Authors: None IWATSUKI, None HAN, None FUKUTI, None OHTSUKA, None KIKUCHI, None AKIBA, None KANEKO
Journal: British Journal of Dermatology (1999)

Acantholytic blisters in pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are caused by a dissociation of desmosomes mediated by autoantibodies against desmoglein (Dsg) 3 and Dsg 1, respectively. The blistering occurs at the suprabasilar level in PV and at the subcorneal level in PF, which corresponds to the distribution of target antigens in the epidermis: there is a more prominent expression of Dsg 1 in the upper layer, whereas Dsg 3 is more prominent in the lower layer. To elucidate the histogenesis of acantholysis, we studied the alterations of the desmosomal components and the expression pattern of Dsg isoforms in the lesional and perilesional epidermis of pemphigus patients. The results demonstrated an internalization of the desmosomes in the lower epidermis of PV, PF and pemphigus vegetans. A similar phenomenon was induced in monolayers of keratinocytes cultured with PV sera. However, little change was observed in E-cadherin expression until acantholysis became manifest. This internalization occurred prior to overt acantholysis, and was frequently associated with the induction of Dsg 2 expression in the basilar or lower layers of the epidermis. These findings indicate an alteration of Dsg isoform expression in subclinical pemphigus lesions, which might be related to the characteristic acantholytic patterns: the suprabasilar layer in PV and the upper epidermis in PF.
Obscure gastrointestinal bleeding due to Meckel’s diverticulum: unusual capsule endoscopic finding as polyp-like lesion
Authors: E. Sy, M.-D. Chen, Y.-J. Yang, Y.-S. Shan
Journal: Endoscopy (2008)

Lower gastrointestinal bleeding is a common complication of Meckel’s diverticulum. Its location within the small bowel, usually 2 feet (60 cm) from the ileocecal valve, makes it difficult to study and not easily accessible with a traditional endoscope. The use of multiple diagnostic modalities may give a false negative result, and capsule endoscopy can be an alternative procedure. In young children, who are not able to swallow the capsule, the capsule can be delivered via gastroscopy with an overtube, with the patient under intravenous anesthesia [1]. Reported complication rates of capsule endoscopy (retention of capsule in stomach and intestine) have ranged from 0.3 % to 20 % [1] [2]. Retention may necessitate endoscopic retrieval or surgical removal [1], or observation may suffice so long as the patient is asymptomatic. Endoscopy may showed the presence of a false lumen [3], a diverticular-like orifice [4], or a blood-filled structure [5]. We report the case of a 15-year-old male patient referred to our department with recurrent lower gastrointestinal bleeding with a hemoglobin concentration of 5 gm/L. He had several diagnostic examinations including computed tomography and magnetic resonance imaging of the abdomen, colonoscopy, Meckel’s scan (technetium 99 m pertechnetate) and red blood cell scan which detected no relevant abnormality. A wireless video capsule endoscopy study revealed a polyp-like lesion, secondary to everted diverticular mucosa, protruding from a false lumen presenting as a dark halo zone in the mid portion of the small bowel ([Fig. 1 a]), 4.5 hours after capsule introduction, with oozing of blood on a picture taken a few minutes later ([Fig. 1 b]). An exploratory laparotomy was performed and a Meckel’s diverticulum with a palpable mass ([Fig. 1 c]) was found. Segmental resection of the bowel was performed. Examination of the specimen revealed everted diverticular mucosa ([Fig. 1 d]), which is compatible with the capsule endoscopic finding ([Fig. 1 a]). An intraoperative finding of Meckel’s diverticulum with early examination of the surgical specimen can avoid further unnecessary palpatory and endoscopic exploration of the entire small bowel.
The Cunningham Case And Blood Usage
Authors: Takashi Okuno
Journal: JAMA (1972)

<h3>To the Editor.—</h3> Court decisions of medicolegal cases, in general, have resulted in a great influence on the quality of a patient's care. In the field of blood banking, an impact by a medicolegal case has been no exception to this. In the Cunningham case in October 1970, a hospital was held strictly liable to a patient who allegedly contracted hepatitis after a blood transfusion. This has had national repercussions. The impact has been especially great on our hospital, a 675-bed general hospital, located within 20 miles of the hospital in which the case took place. In view of this, a study was made to evaluate the scope and extent of the effects of the case on blood usage in our hospital. The study included assessment of 341 charts of patients who received single-unit transfusions in the past three years. In addition, data were collected from the records of the
Analysis of trends in premature mortality by Labour voting in the 1997 general election
Authors: D. Dorling
Journal: BMJ (2001)

increase (11.5%) was seen in Edinburgh and the largest decrease (5.5%) in Aberdeen.Because maternal age has increased, from a mean of 26 in 1990 to 29 in 1998, 5 we corrected for this variable.Breastfeeding rates were calculated in one year steps of maternal age for 1997-8.The maternal age distribution for 1990-1 was taken from the annual report of the registrar general, and breastfeeding rates for maternal age for 1997-8 were substituted into the maternal age distribution for 1990-1.The breastfeeding rate for Scotland would have been 39.4% in 1997-8 if the maternal age distribution had been the same as in 1990-1.Therefore, 2.6% of the observed 6.4% rise in breast feeding can be explained by increase in maternal age.
What Wasn't Taught
Authors: Grace Farris
Journal: Annals of Internal Medicine (2014)

On Being a Doctor16 December 2014What Wasn't TaughtGrace Farris, MDGrace Farris, MDFrom Beth Israel Deaconess Medical Center, Boston, Massachusetts.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M14-1657 Audio Reading - “What Wasn't Taught” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "What Wasn't Taught," by G. Farris. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail “Please do not enter before 11:00 a.m.” The sign, posted on the outer door of the negative pressure room, was held up with the tape typically used for bandages. I looked at the clock on the wall: 6:00 a.m. on a summer day during my intern year.A drop of sweat formed on my brow as I peered through the glazed windows of the door, trying and failing to make out the figure sleeping inside, breathing “private air,” who did not want to be disturbed. I turned my attention to the vital signs chart and medication record that were resting ... Author, Article, and Disclosure InformationAffiliations: From Beth Israel Deaconess Medical Center, Boston, Massachusetts.Corresponding Author: Grace Farris, MD, Beth Israel Deaconess Medical, 330 Brookline Avenue, Boston, MA 02215; e-mail, [email protected]harvard.edu. PreviousarticleNextarticle Advertisement Audio Reading - “What Wasn't Taught” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "What Wasn't Taught," by G. Farris. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 16 December 2014Volume 161, Issue 12Page: 921-922KeywordsBlood sugarFeversFoodHemoglobinHospitalizationsInfectious diseasesInsulinSputumStomachSweat ePublished: 16 December 2014 Issue Published: 16 December 2014 Copyright & PermissionsCopyright © 2014 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
CD40 Ligand Increases Complement C3 Secretion by Proximal Tubular Epithelial Cells
Authors: Giuseppe Castellano, Valentina Cappiello, Nicoletta Fiore, Paola Pontrelli, Loreto Gesualdo, F. Paolo Schena, Vincenzo Montinaro
Journal: Journal of the American Society of Nephrology (2005)

Interstitial leukocyte infiltration is a major finding in tubulointerstitial damage (TID). Infiltrating lymphocytes interact with proximal tubular epithelial cells (PTEC) by means of secreted soluble factors and/or cell contact mechanisms. CD40 expressed onto PTEC can be engaged by CD40L present on T cells. PTEC are able to locally secrete complement C3, which may most likely promote TID. The aim of the study was to investigate the putative action of CD40 ligation on enhancement of C3 secretion by PTEC. Primary human PTEC and stabilized HK-2 cells were used in culture experiments. Cells were stimulated by soluble factors IL-1beta, IFN-gamma, and/or CD40L-expressing murine fibroblast L cells. Analysis of C3 gene expression was evaluated by reverse-transcription PCR and Northern blot. Secreted C3 was assayed by ELISA and a functional hemolytic test on supernatants. Intracellular events were explored by the NF-kappaB-specific inhibitor caffeic acid phenetyl ester (CAPE). Among soluble factors, IL-1beta and IFN-gamma increased C3 gene expression and secretion (two-fold to three-fold versus basal) on both HK-2 and PTEC. CD40 engagement by CD40L upregulated HK-2 C3 secretion by four-fold. IL-1beta did not further increase CD40-induced C3 secretion, whereas IFN-gamma associated with CD40L was the strongest stimulus (30-fold increase). Inhibition of NF-kappaB offset CD40L-induced C3 secretion by 70%. CD40 ligation is able to enhance C3 secretion by PTEC. This cell contact mechanism is in synergism with a T cell-derived soluble factor (IFN-gamma). C3 secretion induced by CD40L may represent a mechanism of amplification of TID associated with lymphocyte infiltration.
THE DISEASE RESISTING POWERS OF THE BODY.A REVIEW OF THE FOUNDATIONS OF NUCLEIN AND SERUM THERAPY.
Authors: CHAS. T. McCLINTOCK
Journal: JAMA (1895)

When it was shown that bacteria were the cause of certain diseases, it was believed for a time, that if these bacteria by any means found an entrance into the body, disease must follow. Until quite recently, popular writers on these questions left this impression with their readers. Pasteur noticed that in case an animal recovered from a germ-caused disease, the germs disappeared from the blood and tissues. He also observed that, in some cases at least, after an animal had recovered from the attack it was more or less immune or insusceptible to the same disease. That this immunity following one attack was true for many of the contagious diseases was indeed a matter of common knowledge. Early in his investigations Pasteur noticed that some animals were readily affected by his microbes, while others were entirely immune; again, that in some cases, a young animal could be infected but
PWE-109 A Metabolomic Profiling Study Of A Chemically-induced Mouse Model Of Intestinal Inflammation
Authors: S Reade, CA Duckworth, T Khalid, A Mayor, R Aggio, DM Pritchard, CS Probert
Journal: Gut (2014)

<h3>Introduction</h3> A non-invasive, IBD-specific biomarker would be clinically useful. We have reported the changes in volatile organic metabolites (VOM) in human IBD. Human studies are limited by the variation in diet and the unpredictability of the disease. Animal models have been established to study many aspects of IBD. We report the first study of VOMs in murine DSS-colitis. <h3>Methods</h3> C57BL/6 female mice at 9–10 weeks old were administered 4.25% dextran sulphate sodium (DSS) in their drinking water for 5 days in order to induce colitis. Clinical parameters of body weight loss, stool consistency and presence of rectal bleeding were assessed daily. Mice were culled at days 0 (n = 11), 5 (n = 11), 8 (n = 11) and 11 (n = 8); colonic, caecal, small bowel contents, mid-large bowel and distal small bowel tissue were taken. VOM profiles for each were analysed using SPME with a CAR/PDMS/DVB fibre and gas chromatography-mass spectrometry. Histology of the distal colon confirmed the presence of colitis; this was graded from none to mild or moderate/severe. <h3>Results</h3> Histology confirmed the presence of colitis. VOM profiles for each sample at days 5, 8 and 11 were compared with day 0. The presence/absence data were used as independent variables in a chi-squared statistical test. In the colonic content, 106 compounds were identified across all groups; 13, 22 and 10 significantly varied with presence/absence between day 0 and day 5, 8 and 11, respectively. A t-test was performed on the abundance of compounds present in at least 60% of samples in one condition. A total of 29 compounds were identified; 9, 6 and 7 VOCs were present at significantly different levels between day 0 and day 5, 8 and 11, respectively. Significance levels for both chi-squared and t-tests were set at p &lt; 0.05 and a fold difference of ³2. Principal component analysis (PCA) of the raw data showed clear separation between the different stages of the disease. A PCA biplot revealed that butanal, propanal, methyl propionate, ethyl acetate, ethyl propionate and 2,3-butanedione were responsible for the main separation between day 0 and day 5/8 of colitis. <h3>Conclusion</h3> Typical clinical and histological features of colitis commenced on day 5, were maximal at day 8 and mice showed signs of recovery between days 8 and 11. The VOM results reflect this timescale, suggesting that metabolic disease profiling is able to represent the different stages of colitis. Further investigation of these differences could deepen our understanding of the pathogenesis of IBD. <h3>Disclosure of Interest</h3> None Declared.
Radiology of the Abdomen: Anatomic Basis
Authors: John L. McClenahan
Journal: JAMA (1977)

In this comprehensive atlas, the pictures are clear and the prose uncluttered; the author makes his way through the convolutions of the peritoneum with grace and nonchalance. Whatever repetition one encounters springs less from redundancy than from a consistent aim to consider the viscera in terms of three dimensions. The basis of Whelan's book is a collection of cross-sections of frozen cadavers sliced through the horizontal, coronal, and sagittal planes. He photographed and labeled these in sequence, drew diagrams, and set these beside appropriate roentgenograms of living subjects. The range extends through both normal and pathological anatomy, and the illustrations include plain films, examinations with contrast agents, body-section roentgenography, and ultrasonograms. Several computerized tomograms are included. Here a frugality of scans suggests that this awesome technique made the publisher's deadline by the skin of its teeth. However, this does not detract from the value of the book. Radiologists using either
The enigma of sepsis
Authors: Niels C. Riedemann, Ren-Feng Guo, Peter A. Ward
Journal: Journal of Clinical Investigation (2003)

Sepsis remains a serious cause of morbidity and mortality, and the pathophysiology of the disease is not clear. The definition of the clinical manifestations of sepsis is ever evolving. This review discusses the search for effective therapeutic interventions, hurdles in translational sepsis research, and new therapies in development in current clinical trials.
PERCIVAL'S CODE: A CHAPTER IN THE HISTORICAL DEVELOPMENT OF MEDICAL ETHICS
Authors: CHAUNCEY D. LEAKE
Journal: JAMA (1923)

Praesans imperfectum — perfectum, plusquam perfectum futurum.—Grotius. In tracing the historical development of medical ethics, two main paths of progression are to be noted: The first is concerned with regulations imposed on physicians by outside, and usually civil, authority; and the second with regulations imposed on physicians by physicians themselves. Covering generally the question of fees, and designed to protect at once the interests both of society and of the individual practitioner, the first line of development began with the medical provisions of the celebrated Babylonian Code of Hammurabi (about 2250 B. C.),<sup>1</sup>and culminated with the lengthy fee statutes enacted by the various European municipal authorities<sup>2</sup>and the American colonial assemblies<sup>3</sup>during the seventeenth and first half of the eighteenth centuries. These embodied the principle of the<i>lex talionis</i>as late as the medical portions of the Forum Judicium of the Visigoths (about 650 A. D.),
THE CHLORIDE EXCRETION TEST (CUTLER-WILDER-POWER TEST) IN ASTHENIA
Authors: Karl E. Paschkis, Alison H. Price
Journal: Journal of Clinical Investigation (1944)

The clinical picture of Addison's disease is well recognized and understood.It is very likely, from analogy with other diseases or deficiencies, that milder cases occur which, for the most part, are not recognized as such.However, the diagnosis of "mild hypoadrenia" made by a number of authors (1 to 5) rests on clinical impression and on the therapeutic effect of substitution therapy alone.These criteria for diagnosis are insufficient and the procedure of treatment is costly.It was therefore decided to investigate the adrenal cor- tical function in asthenic patients. MATERIAL AND METHODSFifty patients have been studied.Of these, 27 com- plained of varying degrees of asthenia.Carbohydrate metabolism was studied by means of the glucose tolerance test, 100 grams of glucose being given orally.Blood sugar determinations were done by Benedict's method.The values reported are therefore "true sugar values."All patients were given a standard mixed diet for at least 5 days prior to testing the glucose tolerance.Orthostatic blood pressure regulation was tested in the majority of cases.As a test for adrenal insufficiency, the chloride con- centration in urine, following a test diet poor in Na, rich in K, has been employed (Cutler, Power, and Wilder (6) ).This test will be referred to as the Cutler test. OBSERVATIONS AND RESULTSSince in Addison's disease there is a high con- centration of Cl in the urine under the conditions of the Cutler test (225 mgm.per cent and above), it was thought that less pronounced adrenal in- sufficiency, or "mild hypoadrenia," might be rec- ognized through a Cl concentration at or above the upper limit of normal.Our findings are tabulated in Table I.As will be discussed later in this paper, the-Cutler test was performed repeatedly in some of the cases.Each case is listed only once in this table, under the highest excretion observed.
Monocyte-mediated Serum-independent Damage to Hyphal and Pseudohyphal Forms of Candida albicans In Vitro
Authors: Richard D. Diamond, Christian C. Haudenschild
Journal: Journal of Clinical Investigation (1981)

Human peripheral blood monocytes attached to Candida albicans hyphae in the absence of serum and damaged the hyphae without completely ingesting them. Attachment and damage was not augmented by the addition of serum. Damage to hyphae was quantitated by a previously developed metabolic assay that measured leukocyte-induced reduction in uptake of [(14)C]cytosine by the hyphae. Use of cells from patients with hereditary disorders of leukocyte function, chronic granulomatous disease, and myeloperoxidase deficiency indicated that myeloperoxidase-independent and nonoxidative mechanisms could sometimes damage hyphae where oxidative mechanisms were impaired. Damage to hyphae by normal monocytes was inhibited by concentrations of sodium azide and sodium cyanide that primarily affect myeloperoxidase activity, as well as by halide-free conditions, catalase, and putative antagonists of hypochlorous acid or singlet oxygen. Iodination of hyphae, a myeloperoxidase and hydrogen peroxide-dependent process of monocytes, was similarly inhibited by sodium azide, sodium cyanide, and catalase. Under anaerobic conditions, damage to hyphae was reduced by 64.0-68.4%. In contrast, inhibitors of potential nonoxidative antifungal mechanisms, iron salts to saturate iron chelators, and polyanionic amino acid polymers to neutralize cationic proteins did not block damage to hyphae by monocytes. Preparations rich in lysosomal granules from fractionated normal monocytes also did not damage hyphae. Overall, it appeared that oxidative mechanisms were most important for damage to hyphae by normal monocytes. Electron microscopy confirmed that Candida hyphae were damaged and probably killed by monocytes, but monocytes appeared to sustain significant damage in the process. In the absence of serum, monocyte cell membranes became closely approximated to Candida cell walls. It appeared that some Candida could escape this partial engulfment, as they were seen floating free with vesicular trilaminar membrane remnants covering hyphal surfaces. In general, monocytes appeared to be damaged by interactions with Candida hyphae more than neutrophils had been in previous studies.