tbuckley/cabot-search huggingface dataset:
Molecular targets for antifibrotic therapy in liver disease: using magic bullets for crossfire rather than a one-sided shotgun attack
Authors: Claus Hellerbrand
Journal: Gut (2013)

The c-Jun-N-terminal kinase (JNK) is a member of the mitogen-activated protein kinase (MAPK) family. Upon activation, JNK regulates various cellular responses, such as differentiation, proliferation, migration, the immune reaction and cell death.1 JNK activation is also involved in multiple pathways in liver physiology and disease pathogenesis.2 

There are three isoforms of JNK in mammals. Whereas JNK3 is mainly expressed in the brain, heart and testis, JNK1 and JNK2 are expressed in most cells, including hepatic parenchymal and non-parenchymal cells. JNK1 and JNK2 have typically been considered to have overlapping or redundant functions. However, it is becoming more and more evident that the JNK isoforms exhibit diverse effects in various cell types, depending on the magnitude and duration of activation.1 

Hepatic fibrosis is a complex and tightly regulated process that involves various cell types and pathomechanisms. It can be considered as a dysregulated wound healing response to chronic hepatic injury. Activated hepatic stellate cells (HSCs) are the primary effector cells responsible for the extensive extracellular matrix accumulation and scar formation. However, the situation is more complex, as several additional cell types, including parenchymal, non-parenchymal, immune infiltrating and bone marrow cells, play an important role in both the pathogenesis and resolution of liver fibrosis.3 Furthermore, hepatocellular proliferation and apoptosis are critical for tissue regeneration and repair, but when dysregulated, these processes contribute to the malignant transformation of hepatocytes and the development of hepatocellular carcinoma (HCC).3 ,4 

Therefore, it is critical to understand the function of distinct JNK isoforms during the various phases and in the various cell types involved in hepatic fibrosis. Examining jnk1 and jnk2 …
Methotrexate-Induced Pulmonary Non-Hodgkin Lymphoma
Authors: Gavin C. Mackie, Judith M. Pohlen
Journal: Clinical Nuclear Medicine (2006)

A 70-year-old woman with a long history of rheumatoid arthritis presented with a history of cough and wheezing. Chest radiography demonstrated pulmonary masses, including a large left lower lobe mass, which exhibited significant F-18 FDG activity on subsequent F-18 FDG PET imaging. Biopsy of the pulmonary mass demonstrated a large B-cell lymphoma. The patient stopped methotrexate and follow-up studies demonstrated considerable reduction in size and metabolic activity of the mass without further intervention.
Tc-99m Sestamibi SPECT Imaging of a Retroesophageal Parathyriod Adenoma
Authors: &NA; D. NGUYEN, BENNETT B. CHIN, ANTONIO J. IMPERIAL
Journal: Clinical Nuclear Medicine (1996)

An 81-year-old woman had a retroesophageal parathyroid adenoma, assessed by Tc-99m sestamibi scintigraphy. SPECT imaging with three-dimensional reconstruction was helpful in the preoperative detection of the ectopic parathyroid tumor and it contributed to successful surgical intervention.
Esophageal capsule endoscopy for screening and surveillance of esophageal varices in patients with portal hypertension
Authors: Roberto de Franchis, Glenn M. Eisen, Loren Laine, Inaki Fernandez-Urien, Juan Manuel Herrerias, Russell D. Brown, Laurel Fisher, Hugo E. Vargas, John Vargo, Julie Thompson, Rami Eliakim
Journal: Hepatology (2008)

Bleeding from esophageal varices (EV) is a serious consequence of portal hypertension. Current guidelines recommend screening patients with cirrhosis with esophagogastroduodenoscopy (EGD) to detect varices. However, the unpleasantness and need for sedation of EGD may limit adherence to screening programs. Pilot studies have shown good performance of esophageal capsule endoscopy in detecting varices. This multicenter trial was designed to assess the diagnostic performance of capsule endoscopy in comparison with EGD. Patients undergoing EGD for screening or surveillance of EV underwent a capsule study previously. The study was designed as an equivalence study, assuming that a difference of <or=10% between capsule endoscopy and EGD in diagnosing EV would demonstrate equivalence. Two hundred eighty-eight patients were enrolled. Endoscopy was for screening in 195 patients and for surveillance of known EV in 93. Overall agreement for detecting EV between EGD and capsule endoscopy was 85.8%; the kappa score was 0.73. Capsule endoscopy had a sensitivity, specificity, positive predictive value, and negative predictive value of 84%, 88%, 92%, and 77%, respectively. The difference in diagnosing EV was 15.6% in favor of EGD. There was complete agreement on variceal grade in 227 of 288 cases (79%). In differentiating between medium/large varices requiring treatment and small/absent varices requiring surveillance, the sensitivity, specificity, positive predictive value, and negative predictive value for capsule endoscopy were 78%, 96%, 87%, and 92%, respectively. Overall agreement on treatment decisions based on EV size was substantial at 91% (kappa = 0.77).We recommend that EGD be used to screen patients with cirrhosis for large EV. However, the minimal invasiveness, good tolerance, and good agreement of capsule endoscopy with EGD might increase adherence to screening programs. Whether this is the case needs to be determined.
Mechanisms Mediating Bradycardia during Coronary Arteriography
Authors: Dwain L. Eckberg, Carl W. White, Michael Kioschos, Francois M. Abboud
Journal: Journal of Clinical Investigation (1974)

Cardiac slowing occurring during diagnostic coronary arteriography was studied in 78 patients. Comparable degrees of slowing occurred with injections into the right and into the left coronary arteries into the contralateral artery, and with injections into the coronary artery giving rise to the sinus node artery and into the contralateral artery. Rapid intracoronary injections of isosmotic dextrose solution produced significantly less slowing than comparable injections of contrast medium. Slow injections of contrast medium produced cardiac slowing comparable to that caused by rapid injections of contrast medium. However, the cardiac slowing was significantly greater than that produced by rapid injections of dextrose solution. Inhalation of 100% oxygen did not alter the heart rate response to injections of contrast medium. Atropine produced dose-related attenuation of cardiac slowing. Bradycardia persisting after cholinergic blockade was significantly greater after injections into the coronary artery supplying the sinus node than it was after injections into the contralateral artery. Coronary arteriography produced transient, occasionally profound, arterial hypotension in 38 of 41 patients in whom arterial pressures were recorded. Arterial pressure did not change in three patients.
Familial Occurrence of Metastasizing Carcinoid Tumors
Authors: C. G. Moertel, M. B. Dockerty
Journal: Annals of Internal Medicine (1973)

Three cases of multicentric and metastasizing carcinoid tumors originating in the terminal ileum were observed in two generations of a single pedigree. This kindred has been characterized by an overall frequency of malignant disease, multiple primary malignant neoplasms, and cancer developing at an early age. In rare cases the carcinoid tumor seems to present as a familial trait.
Straight Arteriovenous Shunt for Long-Term Hemodialysis
Authors: Arthur Shimizu
Journal: JAMA (1971)

Over a 35-month period straight silicone rubber shunts for long-term hemodialysis have been used at St. Joseph's Hospital, Hamilton, Ontario in 30 patients. The average survival time of the arterial cannula varied with the time the patient had been in treatment with the long-term dialysis program: 24.5 months if the patient was admitted to the program in 1967, 14 months if he was admitted to the program in 1968, and 6.6 months if he was admitted to the program in 1969. The main advantage with this type of shunt was that declotting was readily achieved. The average venous-cannula survival time for the present cannula was six months.
Intrahepatic T Cells in Hepatitis B
Authors: Barbara Rehermann
Journal: The Journal of Experimental Medicine (2000)

Clearance of the hepatitis B virus (HBV), a noncytopathic double-stranded DNA virus, requires the coordinated response of innate and adaptive, humoral and cellular immune systems. In more than 90% of immunocompetent adults who become infected, this immune response is quite vigorous, resulting in
Ammonia production by individual segments of the rat nephron.
Authors: D W Good, M B Burg
Journal: Journal of Clinical Investigation (1984)

Ammonia production was measured directly in 10 segments of the rat nephron to determine the relative importance of the segments as sites of renal ammonia production. Tubules were microdissected from normal rats and rats drinking 0.28 M NH4Cl or 0.28 M NaHCO3 for 3-8 d. The segments were incubated in vitro with and without 2 mM glutamine. Ammonia concentrations in the incubation fluid were measured by microfluorometry to determine ammonia production rates. All segments produced ammonia from glutamine. In normal rats, production with glutamine was highest (greater than 5 pmol/min per mm) in the proximal convoluted (S-1), proximal straight (S-3), and distal convoluted tubules, and lowest (less than or equal to 2) in cortical and medullary collecting ducts and thin descending limbs. Metabolic acidosis increased production by 60% in the S-1 segment of the proximal convoluted tubule and by 150% in the S-2 segment of the proximal straight tubule without significant effect in any other segment. Bicarbonate loading decreased production by S-1 but had no effect on S-2 or S-3. Thus, acid-base changes altered production only in specific segments of the proximal tubule. We infer that the bulk of ammonia production occurs in the proximal tubules and that production by collecting ducts can account for only a few percent of renal ammonia production and excretion in the rat.
Herbal Medicine: High-Test Mothers’ Milk
Authors: Cynthia Washam
Journal: Environmental Health Perspectives (2006)

High-Test Mothers' MilkA lack of regulation means that herbal remedies can be ineffective or, conversely, far more potent than users may suspect.Researchers in Taiwan have found a new reason for consumers to be wary of certain herbal remedies: some herbs used in traditional Chinese medicine contain lead, which mothers can pass to their infants through breast milk.The study, published in the 1 February 2006 issue of Science of the Total Environment, adds to the growing evidence that infants can be exposed to potentially dangerous lead levels in utero and through breast milk.Bans on leaded paint and gasoline have caused lead exposure during childhood to plummet.Now scientists are focusing more attention on perinatal exposure to lead via maternal circulating blood levels and breast milk.The neurotoxicant is associated with behavioral problems and diminished intelligence.Although lead has declined in the environment in a number of countries, it may still persist in soil, dust, and water in many parts of the world.Maternal bone lead accumulated during earlier exposure is released during pregnancy and lactation as the body redistributes its calcium stores.Principal investigator Bor-Cheng Han and colleagues originally recruited 72 pregnant women, but only 16 completed the study.The women were interviewed during pregnancy and lactation to collect information on residential and occupational lead exposures, sociodemographic characteristics, and consumption of nutritional supplements, traditional Chinese herbs, alcohol, and tobacco.The women provided breast milk samples weekly from 1 to 60 days postpartum.Nine of the women took traditional herbs, while seven did not.The researchers purchased samples of herbs that the mothers reported taking regularly-Angelicae sinensis radix, Lycii fructus, Zizyphi fructus, and a preparation known as
Abstract 1818: The Aurora B inhibitor ABT-348 is not susceptible to known resistance mechanisms of other Aurora B inhibitors
Authors: Jun Guo, Michael L. Curtin, Robin Heyman, Mark G. Anderson, Patrick A. Marcotte, Paul Tapang, Joann Palma, Luis E. Rodriguez, Amanda Niquette, Jennifer J. Bouska, Daniel H. Albert, Cherrie K. Donawho, Robin R. Frey, Michael Michaelides, Chris Tse, Keith B. Glaser, Omar J. Shah
Journal: Cancer Research (2012)

Abstract The Aurora kinases (Aurora A, B, and C) play essential roles in regulating cell division in mammalian cells and their over-expression in diverse tumor types makes them appealing oncology targets. ABT-348 is a novel, ATP-competitive, multi-targeted kinase inhibitor that exhibits potent activity in multiple solid tumor-derived and leukemia cell lines. ABT-348 is active against Aurora B (IC50 7 nM) and Aurora C (IC50 1 nM), Aurora A (IC50 120 nM). The activity against Aurora B is demonstrated by inhibition of histone H3 phosphorylation and induction of polyploidy. ABT-348 is also active against Aurora-B Y156H, a mutant resistant to other Aurora-B inhibitors. In addition, ABT-348 potently inhibits most members of the VEGFR and PDGFR family of receptor tyrosine kinases, which play a critical role in stromal angiogenesis. In contrast to other Aurora kinase inhibitors, the cellular efficacy of ABT-348 is retained in cells over-expressing P-glycoprotein (Pgp) or breast cancer resistant protein (BCRP), indicating that ABT-348 is not a substrate for these commonly upregulated ATP-binding cassette drug transporters. Consistent with these in vitro studies, ABT-348 was broadly efficacious as a single agent against a wide range of tumor types in vivo, including 3 multi-drug resistant xenograft models. In summary, the potent activity and unique kinase selectivity of ABT-348 against the Aurora kinases and VEGF and PDGF receptor tyrosine kinases, engender its ability to block multiple mechanisms of tumor progression. In addition, our data provide evidence that ABT-348 may be active in tumors resistant to other well-characterized inhibitors targeting Aurora-B. ABT-348 is presently under clinical evaluation in adult patients with advanced solid and hematological neoplasms. 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 1818. doi:1538-7445.AM2012-1818
S25 The Effects of maintenance schedules following pulmonary rehabilitation in patients with chronic obstructive pulmonary disease
Authors: P Browne, S Olive, L Staunton, A Clark, E Wilson, P Galey, E Knights, H Woodhouse, S Robinson, AM Wilson
Journal: Thorax (2013)

<h3>Background</h3> There is good evidence that pulmonary rehabilitation (PR) provides benefit for patients with chronic obstructive pulmonary disease (COPD) in terms of quality of life and daily functioning. However it is generally accepted that the benefits diminish over time. <h3>Methods</h3> We conducted a randomised controlled parallel study of a maintenance programme, following standard PR, consisting of a two hour session of education and strength and endurance training every 3 months versus standard care. Measurements were made, at baseline (prior to a standard PR programme), at randomisation (after successful completion of a PR programme) and after 12 months, of the chronic respiratory questionnaire (CRQ), endurance shuttle walk test (ESWT), EuroQol (EQ5D), hospital anxiety and depression score (HADS) and activity questionnaires. CRQ was also completed every 3 months by post. <h3>Results</h3> 250 (139 male) patients, mean (SD) age of 69.2 (9.2) years, FEV1 41 (16)% predicted, provided informed consent to participate in the study. The mean (95% CI) improvement in CRQ following the initial PR was 0.76 (0.59, 0.93) units. 148 patients entered the randomised part of the study. There remained a significant improvement in CRQ dyspnoea at 12 months compared to baseline for the group as a whole. However, there was no statistically significant differences detected between the intervention and control groups for the CRQ dyspnoea score, which amounted to 0.19 (-0.26, 0.64) units, or other domains of the CRQ. There was no difference in the ESTW distance between the two groups (109.1 (-100.1 to 318.2) metres) or HADS (-0.2 (-2.41,2) units). There was a higher level of self-reported activity, according to the visual analogue score of 16.2/100, in the maintenance group but not the reported metabolic equivalent (MET)-minutes per week. There was no difference in any of the CRQ measures at any of 3 monthly measurements between the intervention and control groups <h3>Conclusion</h3> A maintenance programme of 3monthly 2 hour sessions does not improve outcomes in patients with COPD after 12 months. We cannot recommend that our maintenance programme is adopted. It is likely that a maintenance programme should commence earlier than 3 months and possibly be more intensive.
Mutations in CDMP1 cause autosomal dominant brachydactyly type C
Authors: Alexander Polinkovsky, Nathaniel H. Robin, J. Terrig Thomas, Mira Irons, Audrey Lynn, Frances R. Goodman, William Reardon, Sarina G. Kant, Han G. Brunner, Ineke van der Burgt, David Chitayat, Julie McGaughran, Dian Donnai, Frank P. Luyten, Matthew L. Warman
Journal: Nature Genetics (1997)
The Cause of Appendicitis
Authors: Geo. H. Peake
Journal: BMJ (1911)

system of the ovarian secretion, it is at present impossible -to determine.I believe, with Dr. Ernest Young, that only by careful -clinical notes of these cases carried over several years, together with skiagrams of the joints taken from time to -time, shall we be in a position to say definitely that the -condition we call osteo-arthritis is simply a degenerative process, which may follow in any joint where there has been chronic irritation, be it gouty, infective, rheumatoid, *or due to trauma.-Iam, etc.,
Constitutive β cell expression of IL-12 does not perturb self-tolerance but intensifies established autoimmune diabetes
Authors: Andreas Holz, Kelly Brett, Michael B.A. Oldstone
Journal: Journal of Clinical Investigation (2001)

To analyze the function of the Th1-promoting cytokine IL-12 in vivo, we generated transgenic (tg) mice (RIP-IL12 mice) whose pancreatic β cells constitutively express bioactive IL-12 or one of its components, p35 or p40. In contrast to non-tg littermates or single-tg RIP-p35 and RIP-p40 mice, RIP-IL12 mice developed a marked pancreatic infiltration of lymphocytes and macrophages, mainly around islets. Expression of bioactive IL-12 primarily upregulated transcript levels of IFN-inducible protein-10 (IP-10), RANTES, IFN-γ, and TNF-α in the pancreas. Despite the substantial recruitment of mononuclear cells, no biochemical or clinical disease was evident in the exocrine or endocrine pancreas. Coexpression of lymphocytic choriomeningitis virus (LCMV) proteins with IL-12 in the β cells failed to spontaneously activate or expand antigen-specific anti-self/viral T cells in uninfected tg animals. However, when RIP-IL12 × RIP-LCMV tg mice were infected with LCMV, antigen-specific anti-self/viral T cells were induced, which led to an acceleration in the kinetics and severity of insulin-dependent diabetes mellitus (IDDM). Thus, the ectopic expression of IL-12 does not spontaneously break tolerance and activate antigen-specific T cells in the periphery, but it does worsen ongoing autoimmune disease.
Put down your smartphone and pick up a book
Authors: M. J. Tobin
Journal: BMJ (2014)

Good clinical decision making requires in depth knowledge that comes from reading information in books rather than on screens, writes Martin J Tobin 

Bertrand Russell grumbled in 1924 that “it is impossible to read in America, except on a train, because of the telephone.”1 He continued, “Everyone has a telephone, and it rings all day and most of the night.” Given the ubiquity of distractions today, a landline seems almost Arcadian. 

As we ponder a difficult passage while reading online, our mind wanders to check our email, or the news, or to buy something new. Rather than being deeply engaged with the written word, we are seduced by the false promise of multitasking. For the first time, distractions have become an integral part of the experience of reading.

Online reading involves a different form of literacy than that of the printed page. The eyes bounce and flicker as they dart promiscuously, searching for nuggets of information and quick wins. It is almost as if people go online to avoid reading in the traditional sense.2 The instant presentation of expansive information threatens the more demanding task of the formation …
A comparison of osteoprotegerin with adiponectin and high-sensitivity C-reactive protein (hsCRP) as a marker for insulin resistance
Authors: Eoin P. O'Sullivan, David T. Ashley, Colin Davenport, Lakshmi Penugonda, Grainne Kelleher, Niamh Devlin, Rachel Crowley, Paula O'Shea, Amar Agha, Chris J. Thompson, Donal J. O'Gorman, Diarmuid Smith
Journal: Metabolism (2012)
Management of a Subcapital Fracture and a Shaft Fracture in the Same Femur
Authors: Otto E. Au franc
Journal: JAMA (1961)

Dr. S. Adler*: This 83-year-old woman was brought to the emergency ward of the Massachusetts General Hospital 20 minutes after having been in an automobile accident. She had been a passenger in the back seat. She was complaining of severe pain in the left hip region and the left thigh, moderate pain in the medial portion of the right knee, and tenderness in the right flank. The patient had not lost consciousness. She gave no history of past illnesses important to treatment of her present injury. General examination of the patient showed that her heart was enlarged to the left anterior axillary line. Her blood pressure was 220/110 mm. Hg. There was tenderness but no rebound tenderness in the right flank; otherwise, examination of the abdomen was negative. There was tenderness in the region of the left hip and the left thigh. Motion of the left lower extremity caused pain
Hypertensive-Ischemic Ulcer
Authors: Kenneth R. Woolling
Journal: JAMA (1964)

Three cases of hypertensive-ischemic ulcer of the leg exemplified the unusual situation of infarction of a proximal region of the leg compatible with survival of the distal portion of the limb. This rare type of ischemic necrosis is a complication of the hypertensive state, due to hypertensive occlusive arteriolar disease of the dermal circulation. In most cases complete functional recovery of the extremity occurs eventually. It is important to distinguish the lesion from ischemic ulceration due primarily to arteriosclerosis obliterans, which is often associated with substantial generalized limb ischemia and not infrequently requires amputation.
New and emerging infectious diseases
Authors: Dirk M. Elston
Journal: Journal of the American Academy of Dermatology (2005)

New and emerging diseases present a constant challenge. Globalization of business, international adoption, immigration, and tourism have contributed to the rapid spread of diseases, such as severe acute respiratory syndrome (SARS). Infectious diseases that emerge in Africa or Asia may arrive on US shores within days. This article reviews the new and emerging pathogens important to dermatologists.
Alteration of BIRC3 and multiple other NF-κB pathway genes in splenic marginal zone lymphoma
Authors: Davide Rossi, Silvia Deaglio, David Dominguez-Sola, Silvia Rasi, Tiziana Vaisitti, Claudio Agostinelli, Valeria Spina, Alessio Bruscaggin, Sara Monti, Michaela Cerri, Stefania Cresta, Marco Fangazio, Luca Arcaini, Marco Lucioni, Roberto Marasca, Catherine Thieblemont, Daniela Capello, Fabio Facchetti, Ivo Kwee, Stefano A. Pileri, Robin Foà, Francesco Bertoni, Riccardo Dalla-Favera, Laura Pasqualucci, Gianluca Gaidano
Journal: Blood (2011)