tbuckley/cabot-search huggingface dataset:
Sectional Human Anatomy
Authors: Jerry W. Froelich
Journal: JAMA (1986)

The internal anatomy of the human body has fascinated mankind for many centuries, as evidenced by the popularity and number of anatomy textbooks (<i>Gray's Anatomy</i>is in its 30th edition). Even though human dissection continues to play an important role in the initial learning of internal human anatomy, modern imaging techniques such as computed tomography and magnetic resonance imaging serve as a noninvasive looking glass for the internal human anatomy, as was only dreamed about a decade ago. The authors, Han and Kim, in their book<i>Sectional Human Anatomy: Correlation With Computed Tomography and Magnetic Resonance Imaging</i>, attempt to provide the correlation between cadaveric sectional anatomy, computed tomography, and magnetic resonance imaging. The book is divided into four parts: transverse and coronal sections of the head, brain, and neck, correlated with computed tomography; chest anatomy in both the transverse and sagittal planes, correlated with computed tomography; the abdomen and pelvis
Vigorous activation of monocytes in juvenile autoimmune liver disease escapes the control of regulatory T-cells
Authors: Maria Serena Longhi, Ragai R. Mitry, Marianne Samyn, Astrid Scalori, Munther J. Hussain, Alberto Quaglia, Giorgina Mieli-Vergani, Yun Ma, Diego Vergani
Journal: Hepatology (2009)

Abstract Interface hepatitis, the histological lesion typical of autoimmune hepatitis (AIH), is composed of CD4 and CD8 T lymphocytes and of innate immunity cells, particularly monocytes. Studies in AIH have focused on autoreactive CD4 and CD8 T cells and impairment of CD4+CD25+ regulatory T cells (T-regs), whereas little is known about the role of monocytes and their relationship with T-regs. We have investigated 51 patients with autoimmune liver disease (AILD) and 27 healthy subjects, finding that monocytes were higher in number ( P = 0.044), had a more vigorous spontaneous migration ( P &lt; 0.0005 in patients with inactive disease [ID], and P &lt; 0.001 in those with active disease [AD]), displayed a higher tumor necrosis factor alpha (TNF-α) over interleukin (IL)-10 production ( P = 0.07 in ID and P = 0.0005 in AD), and expressed higher levels of Toll-like receptor (TLR) 4 ( P = 0.048 in ID and P = 0.03 in AD). Addition of conventional T-regs (cT-regs) in AILD enhanced monocyte migration ( P = 0.05 in ID and P = 0.08 in AD), magnified TNF-α over IL-10 production ( P = 0.0005 in ID and P = 0.006 in AD), and markedly increased TLR4 expression levels ( P = 0.01 in ID and P = 0.004 in AD), whereas in normal subjects it either restrained or left unchanged monocyte function. Because a CD127-negative subpopulation within CD4+CD25+ T cells exerts the strongest regulatory activity, we performed additional experiments using purified CD4+CD25+CD127− T cells (true T-regs [tT-regs]). Addition of tT-regs to monocytes decreased monocyte migration ( P = 0.03) and promoted IL-10 production ( P = 0.009), leaving unchanged TLR4 expression in healthy subjects, whereas in patients with AILD it induced only a marginal increase in IL-10 production ( P = 0.045 in ID and P = 0.13 in AD). Conclusion: Monocyte overactivation and inability of cT-regs and tT-regs to restrain it may contribute to the loss of immune tolerance and perpetuation of the autoimmune attack in AILD. (Hepatology 2009.)
Abstract A35: The role of Mdm2 cleavage in p53 function and chemotherapy response
Authors: Trudy G. Oliver
Journal: Clinical Cancer Research (2012)

Abstract Chemotherapy resistance is a major obstacle in cancer treatment, yet the mechanisms of resistance to specific therapies have been largely unexplored in vivo. Employing genetic, genomic, and imaging approaches, we have examined the dynamics of response to a mainstay chemotherapeutic, cisplatin, in multiple mouse models of human non-small cell lung cancer (NSCLC). We show that lung tumors initially respond to cisplatin and exhibit a significant reduction in tumor burden. Prolonged cisplatin treatment promotes the emergence of resistant tumors with enhanced repair capacity that are cross-resistant to platinum analogs, exhibit advanced histopathology, and possess an increased frequency of genomic alterations. Cisplatin-resistant tumors express elevated levels of multiple DNA damage repair and cell cycle arrest-related genes, including p53-inducible protein with a death domain (Pidd). We show that PIDD expression promotes growth arrest and chemotherapy resistance by a mechanism that depends on Caspase-2 and wild-type p53. PIDD-induced Caspase-2 directly cleaves the E3 ubiquitin ligase Mdm2 at Asp 367, leading to loss of the C-terminal RING domain responsible for p53 ubiquitination. As a consequence, N-terminally truncated Mdm2 binds p53 and promotes its stability. Upon DNA damage, p53 induction of the Caspase-2-PIDDosome creates a positive feedback loop that inhibits Mdm2 and reinforces p53 stability and activity, contributing to cell survival and drug resistance. These data establish Mdm2 as a novel cleavage target of Caspase-2 and provide insight into a mechanism of Mdm2 inhibition that impacts p53 dynamics upon genotoxic stress. Our current goals are to: 1) elucidate how cleaved Mdm2 dictates p53 function and 2) create mouse models to manipulate Mdm2 cleavage in vivo in order to interrogate the role of Mdm2 cleavage in lung tumorigenesis and drug response.
Injuries caused by garfish in Papua New Guinea.
Authors: P G Barss
Journal: BMJ (1982)

Garfish, which are found in the Indo-Pacific Ocean areas, have a long, spear-like beak with two marrow jaws and small pointed teeth. They often make sudden leaps while swimming, particularly when attracted by bright lights. In Papua New Guinea people often fish from canoes using a light at night, and serious injuries may be caused by a fish jumping and its beak piercing part of the body. The surface wound may appear deceptively small and innocent, but if the wound is on the chest or abdomen the beak may have penetrated sufficiently deeply to cause internal injuries, and death may result. Patients may have to be admitted to hospital for removal of the beak, which may remain embedded in a limb.
Ia antigens on indeterminate cells of the epidermis: immunoelectronmicroscpic studies of surface antigens
Authors: G. ROWDEN, T.M. PHILLIPS, M. G. LEWIS
Journal: British Journal of Dermatology (1979)

An antiserum against human B-lymphoblastoid cell membrane alloantigens (Ia-like antigens) was used to study the presence of such antigens on dendritic cells in human epidermis. Only Langerhans cells and the majority (85%) of so-called indeterminate cells were positively stained, as shown by immuno-electron microscopy. Fifteen percent of the indeterminate cells were negative and were considered to be immature melanocytes. A relationship exists between the indeterminate cell and the Langerhans cell. A proposal is made concerning emigration of Langerhans cells in response to haptenic stimulation, and the immigration of indeterminate cells to restore the status quo.
Narrative Review: Aspirin Resistance and Its Clinical Implications
Authors: Simon Sanderson, Jon Emery, Trevor Baglin, Ann-Louise Kinmonth
Journal: Annals of Internal Medicine (2005)

Aspirin is currently the most cost-effective drug for the secondary prevention of cardiovascular disease, but treatment failures are relatively common. Several factors have been linked to these recurrent vascular events in patients prescribed aspirin, including smoking, drug interactions, nonadherence, comorbid conditions, and aspirin resistance. The term aspirin resistance has been used to describe not only an absence of the expected pharmacologic effects of aspirin on platelets but also poor clinical outcomes, such as recurrent vascular events, in patients treated with aspirin. Aspirin resistance is perhaps more precisely understood as the phenomenon of measurable, persisting platelet activation that occurs in patients prescribed a therapeutic dose of aspirin and may underlie an unknown proportion of aspirin treatment failures. Key challenges for future research are to standardize a definition of aspirin resistance and to compare whether different measures of platelet activation, either alone or in combination, independently predict cardiovascular events. These challenges must be met before researchers conduct studies to assess the clinical utility of testing on patient outcomes and cost-effective prescribing.
Predicting Lower-Extremity Injuries in High School Football Players
Authors: John L. Clark
Journal: JAMA (1971)

<h3>To the Editor.—</h3> A relationship has been shown in professional football players between ligamentous laxity and knee ligament ruptures requiring surgical correction (<b>212</b>:2236, 1970). A study was conducted with 462 highschool players on 15 teams comprising two leagues to ascertain if a similar relationship held between ligamentous laxity and knee and ankle injuries to such players. Four measures of joint mobility were obtained for each player: (1) the ability to flex the spine with feet together and knees locked, measured on a 10-point scale; (2) the amount of recurvatum of the knee, measured with a goniometer; (3) the angle formed by the two second toes with heels together back to back and feet externally rotated as far as possible, measured to the nearest 5 degrees; and (4) the distance of the knees from the floor while forced down by the seated player's thigh muscles with heels pulled back and
Hyperkalemic Distal Renal Tubular Acidosis Associated with Obstructive Uropathy
Authors: Daniel C. Batlle, Jose A. L. Arruda, Neil A. Kurtzman
Journal: New England Journal of Medicine (1981)

We studied renal function in 13 patients with obstructive uropathy and hyperkalemic metabolic acidosis to characterize the pathogenesis of this disorder. Base-line fractional potassium excretion was lower in all patients than in controls with similar glomerular filtration rates. Acetazolamide was given to 11 patients but failed to increase fractional potassium excretion to normal. In five patients, impaired potassium excretion was associated with decreased ammonium excretion, a urinary pH below 5.5 (5.18±0.07, mean ±S.E.M.), and aldosterone deficiency. In the remaining eight patients, the urinary pH did not fall below 5.5 (6.4±0.2) with acidosis, and we failed to lower the urinary pH and increase fractional potassium excretion to normal by administering a mineralocorticoid and sodium sulfate. A syndrome of hyperkalemic distal renal tubular acidosis may occur in patients with obstructive uropathy. In some patients, this syndrome results from a defect in hydrogen and potassium secretion in the distal nephron rather than from aldosterone deficiency. Obstructive uropathy should be included in the differential diagnosis of hyperkalemic acidosis and renal insufficiency. (N Engl J Med. 1981; 304:373–80.)
Radionuclide Computerized Ventilation Studies
Authors: B MOYSES, E WEITZENBLUM, G METHLIN
Journal: Clinical Nuclear Medicine (1979)

Studies of regional lung function have developed rapidly in the last few years. Xenon-133 is the most frequently used isotope because of its physicochemical and biologic properties. Fixed counters are being replaced by the scintillation camera interfaced to a computer allowing easy acquisition and interpretation of results and numerical data. The use of isotopes other than 133Xe, such as 81 mKr, is less widespread. In this article, a method is described for studying regional ventilation in which the isotope used is 133Xe, the radioactivity is recorded by a scintillation camera, interfaced to a computer and six (or 12) regions for both lungs are selected and investigated. The regional ventilation is expressed as an absolute value in ml/min/ml of ventilated volume as well as the relative contribution in percent of each zone to the total ventilation and volume. To illustrate this method, the results are reported for healthy subjects and for patients with chronic bronchitis and emphysema. Scintigraphs of individual cases are presented. Certain theoretic problems related to calculation of regional ventilation are discussed.
FIRST DEMONSTRATION BY IMMUNO-ELECTRON MICROSCOPY THAT BOTH HEPATIC AND INTESTINAL LIPOPROTEINS CONTRIBUTE TO HUMAN ATHEROSCLEROSIS
Authors: Jesus Gustavo Vazquez Figueroa, Sarah Rinehart, Laura Murrieta, Patrick Battey, Tamio Teramoto, Teruhiko Matsushima, Zhen Qian, Idean B Marvasty, Szilard Voros
Journal: Journal of the American College of Cardiology (2010)
Instinct and Functioning in Health and Disease
Authors: P. MacDonald
Journal: BMJ (1926)

I HAvE within recent years beeni profoundly impressed by a new vista which seems to me to have been opened up by thae workand writings of a laynman-F.Matthias Alexander -with definite bearings upoIl tho science and art of medicine.As Alexander's activities are almost unknown to the profession, although an appreciative review of his book, Constru.ctiveConscious Control of the Individual, appeared in thie BRITISH MEDICAL JOURNAL of May 24th, 1924, and as I. have oome to the conclusioni that there is a primafacie case that his work is of first-class importance, and as, if this be so, investigation by the medical profession is imperative, I decided to make' use of this occasion to attract the attention of some members of the profession to it, i'i the hope that some person or persons better qualified than I am to make such investigations may have their interest aroused.Perlhaps I can start best bv telling you how Alexander began his own investigationis.He is an Australian, anid as a youing man was a reciter, anid had in Australia a great reputation as such, and as a Shakespearian actor.He lost hia3svoice, having contracted what is sometimes called "elergyman's sore throat," presumably a chronic or sub- acute laryngitis.He did what any other man in like
Accuracy of Serial National Institutes of Health Stroke Scale Scores to Identify Artery Status in Acute Ischemic Stroke
Authors: Robert Mikulik, Marc Ribo, Michael D. Hill, James C. Grotta, Marc Malkoff, Carlos Molina, Marta Rubiera, Raquel Delgado-Mederos, Jose Alvarez-Sabin, Andrei V. Alexandrov
Journal: Circulation (2007)

Background— Early recovery after intravenous thrombolysis can be observed in stroke; however, the utility of measuring clinical improvement to assess artery status has not been established. We sought to determine the accuracy of serial National Institutes of Health Stroke Scale (NIHSS) scores to detect complete early recanalization of the middle cerebral artery. Methods and Results— Data from the CLOTBUST trial (Combined Lysis of Thrombus in Brain Ischemia Using Transcranial Ultrasound and Systemic tPA) were used to determine the most sensitive and specific NIHSS-derived parameter to identify complete recanalization. Then, reproducibility was tested against a separate patient population (Barcelona data set). NIHSS scores were determined before tissue plasminogen activator bolus and at 60 and 120 minutes in both data sets. Receiver operating characteristic curves were used to compare test performance. The accuracy of individual cutoffs was demonstrated by sensitivity, specificity, and positive and negative predictive values. A total of 122 patients in the CLOTBUST data set and 98 in the Barcelona data set received 0.9 mg/kg intravenous tissue plasminogen activator [mean age 69±12 versus 72±12 years, 57% male versus 51% male, median NIHSS 16 versus 17 points, mean time from onset to treatment 140±32 versus 177±59 minutes, and complete recanalization of the middle cerebral artery in 19% versus 17%). For identification of recanalization, an NIHSS score reduction of ≥40% offered the best tradeoff, with sensitivity, specificity, positive predictive value, and negative predictive value of 65%, 85%, 50%, and 91% at 60 minutes and 74%, 80%, 58%, and 89% at 120 minutes, respectively. Test performance was equal in the Barcelona data set. Conclusions— Relative changes in serial NIHSS scores can serve as a simple clinical indicator of arterial status after intravenous thrombolysis. Accuracy parameters are affected by the process of recanalization and its varying clinical significance.
Echography and Phonography of Acute Aortic Regurgitation in Bacterial Endocarditis
Authors: ANTHONY N. DeMARIA
Journal: Annals of Internal Medicine (1975)

Since management of acute aortic regurgitation in bacterial endocarditis is enhanced by early recognition, echocardiography and phonocardiography were evaluated in three such cases documented by catheterization and surgery without positive blood cultures and compared to echophonograms of 34 patients with aortic regurgitation of other origins. Endocarditis manifested distinctive, thickened, irregular aortic leaflet echoes with normal systolic excursion and mitral echopreclosure with anterior leaflet fluttering. Mitral preclosure resulted in mid- or end-diastolic crescendo murmur accompanied by soft first heart sound. Aortic echograms in nonendocarditis showed either widened root, diminished leaflet excursion, absence of irregular valvular thickening, or normal leaflets, all without mitral preclosure. This study shows specific echophonographic findings of aortic regurgitation due to endocarditis that enable diagnosis of this condition in the absence of positive blood cultures.
Salvage of ischaemic myocardium by reperfusion: importance of collateral blood flow and myocardial oxygen demand during occlusion
Authors: K. PRZYKLENK, M. T VIVALDI, F. J SCHOEN, J M. O ARNOLD, R. A KLONER
Journal: Cardiovascular Research (1986)

Early reperfusion after coronary artery occlusion is used to treat acute myocardial infarction, but the factors that determine whether salvage of ischaemic myocardium actually occurs remain poorly defined. Differences in collateral blood flow to the region at risk, and haemodynamic variables during occlusion, may contribute to uncertainty as to the time beyond which reperfusion no longer reduces infarct size. To clarify this issue, open chest anaesthetised dogs underwent 1,2,3,4, or 6 hours of left anterior descending coronary artery occlusion followed by reperfusion or permanent occlusion (n=8 per group). Microspheres were injected before occlusion and 15 minutes after occlusion for regional myocardial blood flow determination, and heart rate and arterial blood pressure were measured before occlusion and 10 minutes and 30 minutes after occlusion. At 96 hours after occlusion haemodynamic variables were again measured; the animals were then killed, and occluded bed size was determined by in vitro dye perfusion. The area of necrosis was quantified from histological sections and expressed as a percentage of occluded bed size (AN/OB). If duration of occlusion is considered alone, reperfusion beyond two hours did not salvage ischaemic myocardium in this model. If the results for occlusion equal to and greater than two hours are combined, the mean area of necrosis (27(2)%) was significantly greater than that produced by one hour of occlusion followed by reperfusion (10(4)%). For the animals undergoing occlusion for two or more hours or permanent occlusion, collateral blood flow significantly influenced the area of necrosis. When epicardial flow during occlusion was high (>0.30 ml·min−1 ·g−1 tissue) 13 out of 14 dogs undergoing occlusion for two or more hours or permanent occlusion developed small (AN/OB<27%) infarcts (mean AN/OB 17(2)%). In contrast, when epicardial collateral flow was low (<0.30 ml·min−1·g−1) 14 out of 23 animals had large (AN/OB >27%) infarcts (mean AN/OB 34(3)%). For the 23 dogs in which epicardial flow was low, heart rate during occlusion significantly influenced infarct size: the 14 dogs that developed large infarcts (AN/OB>27%) had a higher mean heart rate (152(6) beats·min−1) than the nine that developed small infarcts (AN/OB <27%) (130(5) beats·min−1; p<0.025). Thus reperfusion at one hour after occlusion salvaged ischaemic myocardium. For occlusions equal to or longer than two hours, infarct size was small when collateral flow to the occluded bed was high; when collateral flow was low, heart rate during occlusion acted together with flow to influence infarct size.
Evidence for renal kinins as mediators of amino acid-induced hyperperfusion and hyperfiltration in the rat.
Authors: A A Jaffa, C P Vio, R H Silva, R J Vavrek, J M Stewart, P F Rust, R K Mayfield
Journal: Journal of Clinical Investigation (1992)

This study examined the role of tissue kallikrein and kinins in renal vasodilation produced by infusion of amino acids (AA). In rats fed a 9% protein diet for 2 wk, intravenous infusion of a 10% AA solution over 60-90 min reduced total renal vascular resistance and increased glomerular filtration rate (GFR) by 25-40% and renal plasma flow (RPF) by 23-30% from baseline. This was associated with a two- to threefold increase in urinary kinin excretion rate. Acute treatment of rats with aprotinin, a kallikrein inhibitor, resulted in deposition of immunoreactive aprotinin in kallikrein-containing connecting tubule cells and inhibited renal kallikrein activity by 90%. A protinin pretreatment abolished the rise in urinary kinins and prevented significant increases in GFR and RPF in response to AA. In a second group of rats pretreated with a B2 kinin receptor antagonist, [DArg Hyp3, Thi5,8 D Phe7]bradykinin, AA infusion raised urinary kinins identically as in untreated controls, but GFR and RPF responses were absent. Aprotinin or the kinin antagonist produced no consistent change in renal function in rats that were not infused with AA.AA-induced increases in kinins were not associated with an increase in renal kallikrein activity. Notably, tissue active kallikrein level fell 50% in AA-infused rats. These studies provide evidence that kinins generated in the kidney participate in mediating renal vasodilation during acute infusion of AA.
Gene therapy for hepatic fibrosis?bringing treatment into the new millennium
Authors: Don C. Rockey
Journal: Hepatology (1999)

We eliminated type beta transforming growth factor (TGF-beta) signaling by adenovirus-mediated local expression of a dominant-negative type II TGF-beta receptor (AdCATbeta-TR) in the liver of rats treated with dimethylnitrosamine, a model of persistent liver fibrosis.In rats that received a single application of AdCATbeta-TR via the portal vein, liver fibrosis as assessed by histology and hydroxyproline content was markedly attenuated.All Ad-CATbeta-TR-treated rats remained alive, and their serum levels of hyaluronic acid and transaminases remained at low levels, whereas all the AdCATbeta-TR-untreated rats died of liver dysfunction.The results demonstrate that TGF-beta does play a central role in liver fibrogenesis and indicate clearly in a persistent fibrosis model that prevention of fibrosis by anti-TGF-beta intervention could be therapeutically useful.