tbuckley/cabot-search huggingface dataset:
Glucagonlike Peptide 2 Analogue Teduglutide
Authors: Lakshmi S. Chaturvedi, Marc D. Basson
Journal: JAMA Surgery (2013)

<h3>Importance</h3> Short bowel syndrome occurs when a shortened intestine cannot absorb sufficient nutrients or fluids. Teduglutide is a recombinant analogue of human glucagonlike peptide 2 that reduces dependence on parenteral nutrition in patients with short bowel syndrome by promoting enterocytic proliferation, increasing the absorptive surface area. However, enterocyte function depends not only on the number of cells that are present but also on differentiated features that facilitate nutrient absorption and digestion. <h3>Objective</h3> To test the hypothesis that teduglutide impairs human intestinal epithelial differentiation. <h3>Design and Setting</h3> We investigated the effects of teduglutide in the modulation of proliferation and differentiation in human Caco-2 intestinal epithelial cells at a basic science laboratory. This was an in vitro study using Caco-2 cells, a human-derived intestinal epithelial cell line commonly used to model enterocytic biology. <h3>Exposure</h3> Cells were exposed to teduglutide or vehicle control. <h3>Main Outcomes and Measures</h3> We analyzed the cell cycle by bromodeoxyuridine incorporation or propidium iodide staining and flow cytometry and measured cell proliferation by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. We used quantitative reverse transcription–polymerase chain reaction to assay the expression of the enterocytic differentiation markers villin, sucrase-isomaltase, glucose transporter 2 (GLUT2), and dipeptidyl peptidase 4 (DPP-4), as well as that of the putative differentiation signals schlafen 12 (SLFN12) and caudal-related homeobox intestine-specific transcription factor (Cdx2). Villin promoter activity was measured by a luciferase-based assay. <h3>Results</h3> The MTS assay demonstrated that teduglutide increased cell numbers by a mean (SD) of 10% (2%) over untreated controls at a maximal 500nM (n = 6,<i>P</i> &lt; .05). Teduglutide increased bromodeoxyuridine-positive cells vs untreated controls by a mean (SD) of 19.4% (2.3%) vs 12.0% (0.8%) (n = 6,<i>P</i> &lt; .05) and increased the S-phase fraction by flow cytometric analysis. Teduglutide reduced the mean (SD) expression of villin by 29% (6%), Cdx2 by 31% (10%), DPP-4 by 15% (6%), GLUT2 by 40% (11%), SLFN12 by 61% (14%), and sucrase-isomaltase by 28% (8%) (n = 6,<i>P</i> &lt; .05 for all). <h3>Conclusions and Relevance</h3> Teduglutide increased Caco-2 proliferation but tended to inhibit intestinal epithelial differentiation. The effects of mitogenic stimulation with teduglutide in patients with short bowel syndrome might be greater if the more numerous teduglutide-treated cells could be stimulated toward a more fully differentiated phenotype.
Judges rule that hospitals have a duty to protect voluntary psychiatric patients
Authors: C. Dyer
Journal: BMJ (2012)

Public institutions, including NHS hospitals, have a positive duty to safeguard the right to life of voluntary psychiatric patients as well as patients who are formally detained, the UK Supreme Court has ruled in a landmark judgment.

Five judges ruled that Pennine Care NHS Trust breached Melanie Rabone’s right to life under article 2 of the European Convention on Human Rights when she was allowed to leave Stepping Hill Hospital in Stockport in April 2005 for two days’ home leave with her parents. She had been admitted to hospital as a voluntary patient after a second suicide …
Acetylcholinesterase blocks cleavage of APP by γ-secretase in 293 cells and mouse brain
Authors: Xin Niu, Xuejin Zhang, Jing Xie, Xuejun Zhang
Journal: Molecular Neurodegeneration (2012)

Background g-Secretase cleaves amyloid precursor protein (APP) to produce Ab peptide, and the secretase is a critical factor in the pathogenesis of Alzheimer’s Disease (AD), whereas acetylcholinesterase (AChE) is a key factor for maintaining normal nerve impulses. However, there has been no published research that focuses on the relationship between these two factors. g-Secretase cleaves various substrates, and loss of function of g-secretase is lethal. Thus, the mechanism by which g-secretase cleaves APP is a key factor in AD pathogenesis. AChE is one of the main targets in the treatment of AD, and AChE inhibitors are commonly used for AD. Currently there is agreement that AChE inhibitors stabilizes acetylcholine (ACh) levels in the brain, which ensures ACh transport among neurons. However, the actual effect is limited. It has been reported that AChE interacts with PS1 and affects its glycosylation. This result suggests a link between AChE and g-secretase. Here, we have tested the effects of AChE on cleavage of APP by g-secretase.
Prognostic Factors in the Treatment of Malignant Pleural Mesothelioma at a Large Tertiary Referral Center
Authors: Raja M. Flores, Maureen Zakowski, Ennapadam Venkatraman, Lee Krug, Kenneth Rosenzweig, Joseph Dycoco, Catherine Lee, Cindy Yeoh, Manjit Bains, Valerie Rusch
Journal: Journal of Thoracic Oncology (2007)
Lung Deposition and Efficiency of Nebulized Amikacin during<i>Escherichia coli</i>Pneumonia in Ventilated Piglets
Authors: Ivan Goldstein, Frederic Wallet, Armelle Nicolas-Robin, Fabio Ferrari, Charles-Hugo Marquette, Jean-Jacques Rouby
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Lung tissue deposition and antibacterial efficiency of nebulized and intravenous amikacin (AMK) were compared in anesthetized and ventilated piglets suffering from a bronchopneumonia produced by the intrabronchial inoculation of Escherichia coli. AMK was administered 24 hours after the inoculation either through an ultrasonic nebulizer (45 mg · kg−1, n = 10) or by intravenous infusion (15 mg · kg−1, n = 8). Piglets were killed 1 hour after a second AMK administration performed 24 hours after the first one, and lung tissue concentrations of AMK and lung bacterial burden were assessed on multiple lung specimens. The amount of nebulized AMK reaching the tracheobronchial tree represented 38 ± 6% of the initial nebulizer AMK charge. After nebulization, AMK lung tissue concentrations were 3- to 30-fold higher than after intravenous administration and were influenced by the severity of lung lesions: 188 ± 175 μg · g−1 in lung segments with mild bronchopneumonia versus 40 ± 65 μg · g−1 in lung segments with severe bronchopneumonia (p < 0.01). Lung bacterial burden was significantly lower in the aerosol group than in the intravenous group (median = 0 colony forming units · g−1 versus median = 5 · 102 colony forming units · g−1, p < 0.001). In conclusion, the deposition of AMK in infected lung parenchyma and the efficiency of bacterial killing were greater after nebulization than after intravenous administration.
ON THE EARLY DIAGNOSIS OF CANCER OF THE TONGUE, AND ON THE RESULTS OF OPERATIONS IN SUCH CASES
Authors: H. T. Butlin
Journal: BMJ (1909)

FEB. 20 IgOI a large increase of lecithin' as compared with the normal.He finds also an increase of lecithin in the faeces in tabes and general paralysis, and a great decrease in the bone marrow.He considers that tabes and paralysis are asso- ciated with a progressive impoverishment of the body in lecithin.It is more probable that there is an impoverishment of lipoids.
BMA angered by below inflation pay offer
Authors: Lynn Eaton
Journal: BMJ (2008)

UK paediatricians will debate a motion of no confidence in the General Medical Council's handling of disciplinary cases involving child protection work, at their professional association's forthcoming meeting.The motion has been put forward by 32 members of the Royal College of Paediatrics and Child Health and will be tabled at the college's annual spring meeting, to be held at York University from 14 April.Many but not all of the motion's signatories are members of Professionals Against Child Abuse, a group formed last year in response to high profile GMC cases against paediatricians.The motion argues that paediatricians are more harshly treated than other specialties, citing cases in which other doctors escaped removal from the register after convictions for assaulting children and viewing child pornography.The motion also accuses the GMC of giving too much weight to serial and vexatious complaints by campaigners and of failing to consider previous investigations that have exonerated paediatricians when starting proceedings against them.This constitutes double jeopardy, the paediatricians argue.Paul Davis, a consultant paediatrician in Cardiff and one of the signatories, said the fear of being struck off was a "powerful deterrent" in discouraging professionals from giving expert testimony and from making child protection referrals."The numbers on the child protection register have declined sharply," he said.A spokesperson for the GMC said, "It is extremely rare for a paediatrician to appear before a panel in connection with child protection work.Since 2004 panels have considered more than 600 cases.Only two could reasonably be said to have been about paediatricians involved in child protection work.Our critics are trying to create the impression that the GMC is intent on unfairly persecuting paediatricians involved in child protection work.Nothing could be further from the truth." Paediatricians debate a motion of no confidence in GMCUK NEWS Review shows growing trend for trials of new cancer drugs to stop early, p 793 WoRld NEWS Germany "has two tier health service" p 796 bmj.comCompany's decision to lengthen lipid lowering trial causes controversy
Nonthrombocytopenic Purpura Due to Miltown (2-Methyl-2-N-Propyl-1,3 Propanediol Dicarbamate)
Authors: W. J. Carmel, T. Dannenberg
Journal: New England Journal of Medicine (1956)

RECENTLY several new drugs have come into widespread use for their sedative or tranquilizing effects. The most widely publicized of these drugs is marketed under the trade names of Miltown and Equanil (2-methyl-2-n-propyl-1,3 propanediol dicarbamate).The pharmacology of this compound, which is related to mephenesin, has been studied by Berger1 and Hendley, Lynes and Berger.2 Its clinical use was reviewed by Selling3 and Borrus.4 The former reported 3 allergic reactions involving fever, urticaria and angioneurotic edema, among 187 patients; the latter observed no hematologic changes in 104 patients and did not mention allergic reactions.The object of this paper is . . .
Molecular mechanism of hypoxia-induced chondrogenesis and its application in in vivo cartilage tissue engineering
Authors: Elise Duval, Catherine Baugé, Rina Andriamanalijaona, Hervé Bénateau, Sylvain Leclercq, Soizic Dutoit, Laurent Poulain, Philippe Galéra, Karim Boumédiene
Journal: Biomaterials (2012)
Journal reverses decision on publishing editorial previously rejected by marketing department
Authors: Owen Dyer
Journal: BMJ (2004)

A journal that refused to print a guest editorial after its marketing department objected has reversed its decision, but the author now refuses to resubmit the article for publication.

The California based journal Dialysis and Transplantation rejected the article after it passed peer review. In a letter to the author, Dennis Cotter, the journal's executive editor, Joseph Herman, said: “Publication of your editorial would, in fact, not be accepted in some quarters … and apparently …
THE ETIOLOGY OF TINEA CRURIS IN KARACHI
Authors: K. A. KHAN, A. A. ANWAR
Journal: British Journal of Dermatology (1969)

Journal Article THE ETIOLOGY OF TINEA CRURIS IN KARACHI Get access K. A. KHAN, K. A. KHAN Department of Microbiology, University of Karachi, Karachi‐32, West Pakistan Search for other works by this author on: Oxford Academic Google Scholar A. A. ANWAR A. A. ANWAR Department of Microbiology, University of Karachi, Karachi‐32, West Pakistan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 81, Issue 11, 1 November 1969, Pages 858–860, https://doi.org/10.1111/j.1365-2133.1969.tb15957.x Published: 01 November 1969 Article history Accepted: 01 March 1969 Published: 01 November 1969
THE LIMIT OF HUMAN LIFE, AND HOW TO LIVE LONG.
Authors: R. H. DALTON
Journal: JAMA (1893)

By common consent, human life has been limited to three score years and ten since the time of King Solomon, with a small minority surpassing that limit and a few who have lived a hundred years or more; and with conditions of life unchanged the period would doubtless remain the same. The conditions of life, however, have already changed. The influence of hygiene and measures of sanitation practiced since the beginning of the last half century, together with the wonderful discoveries and inventions employed for the comfort and protection of mankind generally, have unquestionably raised the lifetime of a generation several years. Moreover, this rising average must continue while popular education of the masses is becoming a uniyersal policy, and the laws of health laid open to the people by the secular press everywhere; and now even the octogenarian may hope to spin out a few more years. To man,
A Stereoscopic Atlas of Human Anatomy. Section V: The Abdomen
Authors: William T. Kabisch
Journal: JAMA (1961)

This section on the abdomen, the fifth of a series intended to illustrate the gross anatomy of the human body, consists of 140 stereoscopic kodachrome photographs of cadaver dissections. Previous issues dealt with the central nervous system, head and neck, upper extremity, and thorax. Sections on the pelvis, lower extremity, and back are in preparation.  Within each of the major areas, a general view introduces the series of dissections and is followed by close-up views showing details of the anatomy at higher magnifications. An invaluable part of this volume is the labeled atlas of line drawings made from, and accompanying, each Kodachrome pair. Anatomical nomenclature adopted by the Sixth International Congress of Anatomists, Paris, 1955, is used for the first time in this section.  The View-Master circular reels are well made and can be used in a hand viewer or in a stereoprojector. Special viewing glasses are required for viewing
Hepatic transforming growth factor beta gives rise to tumor-initiating cells and promotes liver cancer development
Authors: Kun Wu, Jin Ding, Cheng Chen, Wen Sun, Bei-Fang Ning, Wen Wen, Lei Huang, Tao Han, Wen Yang, Chao Wang, Zhong Li, Meng-Chao Wu, Gen-Sheng Feng, Wei-Fen Xie, Hong-Yang Wang
Journal: Hepatology (2012)

Liver cirrhosis is a predominant risk factor for hepatocellular carcinoma (HCC). However, the mechanism underlying the progression from cirrhosis to HCC remains unclear. Herein we report the concurrent increase of liver progenitor cells (LPCs) and transforming growth factor-β (TGF-β) in diethylnitrosamine (DEN)-induced rat hepatocarcinogenesis and cirrhotic livers of HCC patients. Using several experimental approaches, including 2-acetylaminofluorene/partial hepatectomy (2-AAF/PHx) and 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-elicited murine liver regeneration, we found that activation of LPCs in the absence of TGF-β induction was insufficient to trigger hepatocarcinogenesis. Moreover, a small fraction of LPCs was detected to coexpress tumor initiating cell (T-IC) markers during rat hepatocarcinogenesis and in human HCCs, and TGF-β levels were positively correlated with T-IC marker expression, which indicates a role of TGF-β in T-IC generation. Rat pluripotent LPC-like WB-F344 cells were exposed to low doses of TGF-β for 18 weeks imitating the enhanced TGF-β expression in cirrhotic liver. Interestingly, long-term treatment of TGF-β on WB-F344 cells impaired their LPC potential but granted them T-IC properties including expression of T-IC markers, increased self-renewal capacity, stronger chemoresistance, and tumorigenicity in NOD-SCID mice. Hyperactivation of Akt but not Notch, signal transducer and activator of transcription 3 (STAT3), or mammalian target of rapamycin (mTOR) was detected in TGF-β-treated WB-F344 cells. Introduction of the dominant-negative mutant of Akt significantly attenuated T-IC properties of those transformed WB-F344 cells, indicating Akt was required in TGF-β-mediated-generation of hepatic T-ICs. We further demonstrate that TGF-β-induced Akt activation and LPC transformation was mediated by microRNA-216a-modulated phosphatase and tensin homolog deleted on chromosome 10 (PTEN) suppression.Hepatoma-initiating cells may derive from hepatic progenitor cells exposed to chronic and constant TGF-β stimulation in cirrhotic liver, and pharmaceutical inhibition of microRNA-216a/PTEN/Akt signaling could be a novel strategy for HCC prevention and therapy targeting hepatic T-ICs.
Macrophages derived from infiltrating monocytes mediate autoimmune myelin destruction
Authors: Michael T. Heneka
Journal: The Journal of Experimental Medicine (2014)

The Journal of Experimental Medicine < I D > j e m . 2 1 1 8 i n s i g h t 1 f i g 1 .j p e g < / I D > Macrophages mediate myelin destruction in multiple sclerosis (MS), but the origin of these cells (whether derived from tissue-resident microglial cells or infiltrating monocytes) has been widely debated.Now, Yamasaki and colleagues distinguish these cells in a mouse model of MS and show that monocyte-derived macrophages (MDMs) mediate myelin destruction, whereas microglia-derived macrophages (MiDMs) clear up the debris.Previous attempts to decipher the nature and role of cells involved in autoimmune demyelination have proven challenging.Although ontogenetically distinct, it has not been possible to distinguish macrophages derived from tissue-resident or -infiltrating cells based on morphological features (by light microscopy) or surface phenotype.Previous attempts to address this problem include parabiosis and bone marrow transplantation after irradiation, both strategies with substantial technical problems and limitations.< I D > j e m . 2 1 1 8 i n s i g h t 1 f i g 2 .e p s < / I D > Yamasaki et al. studied double chemokine receptor (CCR2-RFP + ; CX3CR1-GFP + ) mice in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS.Inflammatory lesions were filled with both MDMs and MiDMs.Confocal immunohistochemistry, serial block-face scanning electron microscopy (SBF-SEM), and subsequent 3D reconstruction revealed that myelin destruction was initiated by MDMs, often at the nodes of Ranvier, whereas MiDMs were not detected at this site.Disruption of MDM infiltration by CCR2 deficiency completely abolished the presence of macrophages at the nodes of Ranvier.Gene expression profiling of both cell types at disease onset revealed substantial differences, which correlated well with the observations obtained by SBF-SEM.MDMs expressed genes attributable to effector functions, including those involved in phagocytosis and cell clearance.In contrast, MiMD gene expression patterns at disease onset were characteristic of a repressed metabolic state.This paper sets a new standard for further studies in the field.For the first time, MDMs and MiDMs have been clearly differentiated and their morphological relationship to axoglial structures has been analyzed.The finding that MDMs rather than MiDMs initiate myelin destruction at disease onset should enable this cell population to be targeted more effectively in future.The next stage is to verify these findings in human tissue.Future research should also assess further time points over the entire disease course, in particular to exclude that MiDMs do not join MDMs at the node of Ranvier at later stages of disease.A precise distinction between local and infiltrating cell populations may also contribute to a better understanding of pathogenesis in other CNS disorders such as stroke and brain trauma and will hopefully lead to the development of new therapeutic strategies.
Axl receptor activation mediates laminar shear stress anti-apoptotic effects in human endothelial cells
Authors: D DARCANGELO, V AMBROSINO, M GIANNUZZO, C GAETANO, M CAPOGROSSI
Journal: Cardiovascular Research (2006)

Laminar Shear Stress (SS) induces cytosolic acidification and protects endothelial cells (ECs) from apoptosis. Our prior studies showed that acidification protects ECs from serum deprivation-induced apoptosis by a mechanism directly involving Axl-receptor activation. Aim of the present study was to determine whether the anti-apoptotic action of SS involves acidification-dependent Axl activation.Axl mRNA and protein levels were significantly higher (5 and 8 fold, respectively) in ECs exposed to SS (12 dyne/cm2), compared to static culture (ST). This effect was dependent on the presence of bicarbonate ion and blocked by the anion exchangers inhibitors, DIDS and SITS. Moreover, DIDS markedly inhibited the anti-apoptotic action of SS. Notably, after 5 min of SS exposure, Axl-receptor was tyrosine-phosphorylated. The over-expression in human ECs of an Axl-receptor soluble form completely reverted the anti-apoptotic SS effect. Since laminar SS exerts its effects through the activation of integrin-dependent pathways, we examined whether Axl might be associated with the alphavbeta3 integrin complex known to be activated by SS. Co-immunoprecipitation experiments indicate that 5 min of ECs exposure to SS induced Axl-receptor/beta3-integrin complex formation, suggesting their functional association.These results indicate that Axl receptor activation modulates laminar SS anti-apoptotic effects possibly through its association with specific integrin-complexes.
Acute pancreatitis complicating therapy of Hodgkin disease: A case report
Authors: Oliver A. Batson, Richard F. Branda
Journal: American Journal of Hematology (1990)

Abstract Acute pancreatitis developed in a young woman with disseminated Hodgkin disease coincident with cytotoxic treatment. Despite concerns about possible drug‐related causes, chemotherapy was continued without further gastrointestinal consequences. This case indicates that pancreatitis need not necessarily alter therapeutic plans for Hodgkin disease. Causes of pancreatitis in the setting of malignancy are reviewed.