tbuckley/cabot-search huggingface dataset:
Mannose receptor interacts with Fc receptors and is critical for the development of crescentic glomerulonephritis in mice
Authors: Konstantia-Maria Chavele, Luisa Martinez-Pomares, Jan Domin, Samantha Pemberton, Stuart M. Haslam, Anne Dell, H. Terence Cook, Charles D. Pusey, Siamon Gordon, Alan D. Salama
Journal: Journal of Clinical Investigation (2010)

Crescentic glomerulonephritis (CGN), which frequently results in acute and chronic kidney disease, is characterized by and dependent on glomerular infiltration by macrophages. The mannose receptor (MR) is a pattern recognition receptor implicated in the uptake of endogenous and microbial ligands by macrophages, mesangial cells (MCs), and selected endothelial cells. It is upregulated on alternatively activated macrophages (i.e., macrophages associated with tissue repair and humoral immunity) and involved in antigen presentation to T cells. We used the mouse model of nephrotoxic nephritis to investigate the role of MR in CGN. Our results demonstrate what we believe to be a novel role for MR in the promotion of CGN that is independent of adaptive immune responses. MR-deficient (Mr-/-) mice were protected from CGN despite generating humoral and T cell responses similar to those of WT mice, but they demonstrated diminished macrophage and MC Fc receptor-mediated (FcR-mediated) functions, including phagocytosis and Fc-mediated oxygen burst activity. Mr-/- MCs demonstrated augmented apoptosis compared with WT cells, and this was associated with diminished Akt phosphorylation. Macrophage interaction with apoptotic MCs induced a noninflammatory phenotype that was more marked in Mr-/- macrophages than in WT macrophages. Our results demonstrate that MR augments Fc-mediated function and promotes MC survival. We suggest that targeting MR may provide an alternative therapeutic approach in CGN while minimizing the impact on adaptive immune responses, which are affected by conventional immunosuppressive approaches.
CONGENITAL CYSTIC KIDNEY.
Authors: F. B. LUND
Journal: JAMA (1906)

Congenital cvstic disease of the kidney is a rare affection and one which so far appears to have interested the pathologists far more than clinical observers. The pathology of the disease presents an abundance of controversial literature, for the reason, perhaps, that the condition has been hard to explain and has afforded abundant opportunity for discussion and theorizing, but we, as practitioners of surgery, must not forget that the disease is of eminent practical and surgical importance, and that, although we may not meet with it on the operating table many times in a long surgical career, it is well worth while, when those times come, to be prepared by a previous consideration of its clinical history, prognosis and surgical treatment. It is a disease which frequently runs its course without a diagnosis being made during life, death occurring from uremia or cerebral hemorrhage, due to kidney insufficiency. The real
Differential Effects of Immunosuppressants on Lymphocyte Function
Authors: Alan Winkelstein
Journal: Journal of Clinical Investigation (1973)

In vitro and in vivo parameters of T lymphocyte function were evaluated in guinea pigs following treatment with the “cycle-active” drugs, 6-mercaptopurine (6MP) and methotrexate, and the “non-cycle-active” alkylating agent, cyclophosphamide. Commencing at the time of sensitization to tuberculin protein, animals were treated with an 8 day course of one of the cytotoxic drugs. This regimen either reduced or abolished the cutaneous response to PPD. The two cycle-active drugs inhibited the in vitro lymphoproliferative response to PPD and suppressed the elaboration of migration inhibition factor (MIF) by lymph node cells. However, these agents did not reduce blood lymphocytes, deplete the cellularity of the thymic dependent areas of peripheral tissues, or alter the in vitro response of lymph node cells to the nonspecific mitogen PHA. In contrast, treatment with cyclophosphamide was associated with a reduction in peripheral blood and tissue lymphocytes and impaired responses to PHA by residual lymph node cells. In vitro proliferative responses to PPD were inhibited but the capacity of lymph node cells to elaborate MIF was not suppressed. In addition to their effects on antigen-reactive lymphocytes, all three drugs significantly reduced the number of macrophages in induced peritoneal exudates. With respect to immunosuppressive activities, results of these investigations suggest that the noncycle-active agents affect both intermitotic and dividing T lymphocytes without impairing certain intermitotic functions of residual cells. The cycle-active drugs have a more restricted toxicity limited to those T lymphocytes which have been stimulated to undergo active DNA synthesis by antigenic challenge.
Erysipeloid sporotrichosis in a woman with Cushing’s disease
Authors: Sam Kim, Matthew H. Rusk, William D. James
Journal: Journal of the American Academy of Dermatology (1999)

A woman presented with a swollen red leg of 2 weeks’ duration. Culture of the skin biopsy specimen confirmed this to be an infection caused by Sporothrix schenckii. Systemic evaluation led to the diagnosis of Cushing’s disease and explained the unusual morphology. Treatment-related complications are also discussed. (J Am Acad Dermatol 1999;40:272-4.)
Using functional near infrared spectroscopy to measure moral decision-making: effects of agency, emotional value, and monetary incentive
Authors: Megan Strait, Matthias Scheutz
Journal: Brain-Computer Interfaces (2014)

AbstractThe prefrontal cortex (PFC) has been investigated extensively with functional magnetic resonance imaging (fMRI) and identified as a neural substrate central to emotion regulation and decision-making, particularly in the context of utilitarian moral dilemmas. However, there are two important limitations to prior work: (1) fMRI imposes strict constraints on the physical environment of the participant and (2) experimental manipulations have yet to consider the role of agency and personal incentive on both brain-based and behavioral correlates. To address the first limitation, we investigated functional near infrared spectroscopy (NIRS), which showed it was a potential alternative to fMRI for observing the decision-making processes in a less-constrained environment [Citation1]. To address the second, we examined the role of agency in deciding moral and non-moral dilemmas and whether the influences can be further modulated by way of monetary incentives. Our findings show that all three factors exert influences on both behavioral and neural metrics. In particular, emotional value increases, whereas incentive decreases, prefrontal hemodynamic activity. Moreover, agency interacts with both emotional value and incentive, further polarizing the behavioral and neural metrics with regard to human patients.Keywords: functional near infrared spectroscopy (NIRS)decision-makingmoral dilemmaagencyincentive
Planning for closure: the role of special administrators in reducing NHS hospital services in England
Authors: A. M. Pollock, D. Price, E. Kondilis, A. Freitag, L. Harding-Edgar
Journal: BMJ (2013)

A proposed amendment to the law will give special administrators powers to reconfigure health services well beyond those provided by the trusts they are administering. <b>Allyson Pollock and colleagues</b> argue that this will undermine equal access to care in England
Management of cystic pancreatic lesions found incidentally
Authors: M. Barthet, B. Napoléon, L. Palazzo, M. Chemali, J.-C. Letard, R. Laugier, J.-P. Arpurt, J. Boyer, C. Boustière, J.-M. Canard, J. Cassigneul, P.-A. Dalbiès, J. Escourrou, G. Gay, T. Ponchon, B. Richard-Molard, D. Sautereau, G. Tucat, B. Vedrenne
Journal: Endoscopy (2007)

Solid and cystic pancreatic lesions are increasingly being found incidentally, owing to improved pancreatic imaging techniques, with ultrasonography, multidetector computed tomography (CT) scanning and magnetic resonance imaging (MRI), and a better knowledge of the characteristics and incidence of these lesions. One in every 5000 screening ultrasonographies reveals a potentially malignant cystic tumor of the pancreas [1]. Similarly to intraductal papillary mucin-producing tumors (IPMTs), more than 10 % of pancreatic cystic tumors are identified incidentally [2]. Malignant cystic tumors are frequently symptomatic and it is therefore highly probable that a cystic tumor which is discovered accidentally will be benign [2] [3]. The proportion of cystic tumors that are incidentally identified is increasing in France and the USA, rising from 8.8 % in the 1980s to 11.9 % in the 1990s [2].
One third of diagnoses of asthma in Canada are wrong, study finds
Authors: D. Spurgeon
Journal: BMJ (2008)

Almost a third of people diagnosed as having asthma in Canada did not have the condition when retested using clinical guidelines, a study has found ( CMAJ 2008;179:1121-31, doi:10.1503/cmaj.081665).

The study shows “a major problem in our system of asthma care: rather than just being overdiagnosed, asthma is misdiagnosed,” said Matthew Stanbrook, deputy editor of CMAJ , the journal of the Canadian Medical Association, and Alan Kaplan, chairman of the Family Physician Airways Group of Canada, in an accompanying editorial ( CMAJ 2008;179:1099-100, doi:10.1503/cmaj.081665).

Such misdiagnosis …
Nondysenteric Intestinal Amebiasis
Authors: Martin S. Wolfe
Journal: JAMA (1973)

Diloxanide furoate, an investigational, amebicidal drug in the United States, was given in a ten-day course of 500 mg three times a day. This therapy led to parasitologic and symptomatic cure in all 12 asymptomatic cyst carriers and in 52 of 65 patients with nondysenteric, symptomatic, intestinal amebiasis who had all contracted<i>Entamoeba histolytica</i>infections while abroad. Criteria for cure were the absence of E histolytica parasites in three complete stool examinations, one and three months following completion of treatment, and complete or marked symptomatic improvement. Excessive flatulence was a common, but the only significant side effect. The high effectiveness (83% cure rate), relative ease of administration, and minimal toxicity of diloxanide furoate indicates that this drug has numerous advantages over other primarily luminal-acting amebicides presently available in this country for the treatment of chronic amebiasis.
Comparative outcome of reduced intensity and myeloablative conditioning regimen in HLA identical sibling allogeneic haematopoietic stem cell transplantation for patients older than 50 years of age with acute myeloblastic leukaemia: a retrospective survey from the Acute Leukemia Working Party (ALWP) of the European group for Blood and Marrow Transplantation (EBMT)
Authors: M Aoudjhane, M Labopin, N C Gorin, A Shimoni, T Ruutu, H-J Kolb, F Frassoni, J M Boiron, J L Yin, J Finke, H Shouten, D Blaise, M Falda, A A Fauser, J Esteve, E Polge, S Slavin, D Niederwieser, A Nagler, V Rocha
Journal: Leukemia (2005)
Gastroenterology services: a regional review.
Authors: C D Holdsworth, M Atkinson
Journal: BMJ (1984)

Gastroenterology has developed on a national scale as a medical specialty only within the past 20 years.The main reason has been the increasing sophistication of diagnostic and therapeutic methods, which has led to a demand for clinicians to provide these skillsin particular a fibreoptic endoscopy service.Recommendations on the manpower, space, and equipment needed to provide an adequate service were published in 1979 in a report of the Gastroenterology Liaison Committee, on which the British Society of Gastroenterology, the Royal College of Physicians, and the Department of Health and Social Security were represented.1 Since then, though a report has been published on the work carried out by an individual unit,2 there has been no attempt to assess the impact of the 1979 report or the adequacy of present services over a wider area.This paper represents the results of a survey of gastroenterology services of one regional health authority in England. SurveyThe Trent Regional Health Authority has 12 districts, of which three (Nottingham, Sheffield, and Leicestershire) are teaching districts, and it has three medical schools.The population of the region is 4 341 000, and the figure shows the distribution in each district.In mid-1982 all physicians in the region with an interest in gastroenterology were circulated with a questionnaire, to which all replied.The results were summarised and recirculated for corrections to be made.
Clinical Ethics: Biomedical Ethics at the Bedside
Authors: Edmund D. Pellegrino
Journal: JAMA (1988)

The articles chosen for this issue of<i>JAMA</i>illustrate various aspects of clinical ethics, the emergent genre of medical ethics that focuses on the process of ethical decision making in its clinical setting. Clinical ethics moves ethics from its place in the classroom and ethicist's study to its origins at the bedside of sick people, where the dilemmas the ethicist contemplates are generated and where ethical discussion ultimately must end in decision and action.<sup>1,2</sup> These articles describe how the move to the bedside is reshaping the way medical ethical decisions are made in the hospital, the clinic, and the physician's office. In democratic, educated, and morally heterogeneous societies like ours, the intuitive and idiosyncratic way of making ethical choices is no longer tenable. Medical ethics has become a public affair. The physician's decisions must now be justified to patients and their families, one's colleagues, and the courts. As a
p53 and NF-κB Coregulate Proinflammatory Gene Responses in Human Macrophages
Authors: Julie M. Lowe, Daniel Menendez, Pierre R. Bushel, Maria Shatz, Erin L. Kirk, Melissa A. Troester, Stavros Garantziotis, Michael B. Fessler, Michael A. Resnick
Journal: Cancer Research (2014)

Abstract Macrophages are sentinel immune cells that survey the tissue microenvironment, releasing cytokines in response to both exogenous insults and endogenous events such as tumorigenesis. Macrophages mediate tumor surveillance and therapy-induced tumor regression; however, tumor-associated macrophages (TAM) and their products may also promote tumor progression. Whereas NF-κB is prominent in macrophage-initiated inflammatory responses, little is known about the role of p53 in macrophage responses to environmental challenge, including chemotherapy or in TAMs. Here, we report that NF-κB and p53, which generally have opposing effects in cancer cells, coregulate induction of proinflammatory genes in primary human monocytes and macrophages. Using Nutlin-3 as a tool, we demonstrate that p53 and NF-κB rapidly and highly induce interleukin (IL)-6 by binding to its promoter. Transcriptome analysis revealed global p53/NF-κB co-regulation of immune response genes, including several chemokines, which effectively induced human neutrophil migration. In addition, we show that p53, activated by tumor cell paracrine factors, induces high basal levels of macrophage IL-6 in a TAM model system [tumor-conditioned macrophages (TCM)]. Compared with normal macrophages, TCMs exhibited higher p53 levels, enhanced p53 binding to the IL-6 promoter, and reduced IL-6 levels upon p53 inhibition. Taken together, we describe a mechanism by which human macrophages integrate signals through p53 and NF-κB to drive proinflammatory cytokine induction. Our results implicate a novel role for macrophage p53 in conditioning the tumor microenvironment and suggest a potential mechanism by which p53-activating chemotherapeutics, acting upon p53-sufficient macrophages and precursor monocytes, may indirectly impact tumors lacking functional p53. Cancer Res; 74(8); 2182–92. ©2014 AACR.
Novel recurrent genetic imbalances in human hepatocellular carcinoma cell lines identified by comparative genomic hybridization
Authors: Drazen B. Zimonjic, Catherine L. Keck, Snorri S. Thorgeirsson, Nicholas C. Popescu
Journal: Hepatology (1999)

To search for recurrent and specific genomic alterations in human hepatocellular carcinoma (HCC), we examined 18 cell lines by comparative genomic hybridization (CGH), a molecular cytogenetic approach that allows positional identification of gains and losses of DNA sequences of the entire tumor genome. We report here a distinct pattern of multiple recurrent DNA copy-number gains and losses that include alterations frequently seen in other neoplasias as well as changes potentially specific for HCC. The most frequent gains were localized on 1p34.3-35, 1p33-34.1, 1q21-23, 1q31-32, 6p11-12, 7p21, 7q11.2, 8q24.1-24.2, 11q11-13, 12q11-13, 12q23, 17q11. 2-21, 17q23-24, and 20p11.1-q13.2. Recurrent losses were mapped on 3p12-14, 3q25, 4p12-14, 4q13-34, 5q21, 6q25-26, 8p11.2-23, 9p12-24, 11q23-24, 13q12-33, 14q12-13, 15q25-26, 18q11.2-22.2, and 21q21-22. Seventeen genomic imbalances are novel in HCC, thus extending significantly the map of genetic changes and providing a starting point for the isolation of new genes relevant in pathogenesis of liver neoplasia, as well as providing molecular probes for both diagnosis and monitoring treatment of the disease.
Acute Oxaliplatin-Induced Peripheral Nerve Hyperexcitability
Authors: Richard H. Wilson, Tanya Lehky, Rebecca R. Thomas, Mary G. Quinn, Mary Kay Floeter, Jean L. Grem
Journal: Journal of Clinical Oncology (2002)

PURPOSE: Oxaliplatin is a novel platinum compound with clinical activity in several malignancies. Neurotoxicity is dose-limiting and occurs in two distinct forms, an acute neurologic symptom complex that occurs within hours or days of therapy and a chronic, cumulative sensory neuropathy. PATIENTS AND METHODS: Patients were treated in a phase I study designed to establish the maximum-tolerated dose of capecitabine given with oxaliplatin. Because of the unusual neurosensory toxicity of oxaliplatin, detailed neurologic examination, needle electromyography (EMG), and nerve conduction studies (NCS) were performed before and the day after oxaliplatin in a subset of 13 patients. Carbamazepine therapy was tried in 12 additional patients to determine whether the neurologic effects might be relieved. RESULTS: All patients experienced acute, reversible neurotoxicities with oxaliplatin. Symptoms included paresthesias, dysesthesias, cold hypersensitivity, jaw pain, eye pain, pain in the arm used for drug infusion, ptosis, leg cramps, and visual and voice changes. Serial EMG and NCS revealed striking signs of hyperexcitability in motor nerves after oxaliplatin. In patients who achieved therapeutic levels, carbamazepine did not alter the clinical or electromyographic abnormalities. CONCLUSION: The acute neurotoxicity seen with oxaliplatin is characterized by peripheral-nerve hyperexcitability, and the findings are similar to the clinical manifestations of neuromyotonia. Carbamezepine, which provides symptomatic relief in acquired neuromytonia, did not seem to be beneficial. Efforts to identify a successful neuroprotectant strategy would have a major impact on improving patient quality of life and the ability to deliver full doses of oxaliplatin.
Families with Autosomal Dominant Brachydactyly Type E, Short Stature, and Severe Hypertension
Authors: Hakan R. Toka
Journal: Annals of Internal Medicine (1998)

Background: Rare, monogenic forms of hypertension may give insight into novel mechanisms relevant to essential hypertension. Autosomal dominant hypertension with brachydactyly has been documented in a single Turkish kindred; the gene was mapped to chromosome 12p. Objective: To describe the molecular genetics of additional families with autosomal dominant hypertension and brachydactyly. Design: Case series. Setting: Tertiary care medical centers. Patients: An 11-member Canadian family and a 7-member U.S. family, neither of Turkish background, with autosomal dominant hypertension and type E brachydactyly. Measurements: Clinical evaluation, genotyping, and haplotype analyses. Results: The mode of inheritance, the type E brachydactyly, and the propensity for stroke were consistent with autosomal dominant hypertension with brachydactyly. The same markers on chromosome 12p cosegregated with the phenotype in the families. A haplotype analysis strongly supported the conclusion that these families have a molecular defect in the same gene. Conclusions: The syndrome of autosomal dominant hypertension and brachydactyly is not confined to patients of Turkish origin. All persons with brachydactyly should have their blood pressure measured, and the syndrome should be considered if hypertension is found.
Androstenedione Is the Preferred Androgen Source in Hormone Refractory Prostate Cancer—Response
Authors: Christopher M. Hovens, Matthew K.H. Hong, Niall M. Corcoran
Journal: Clinical Cancer Research (2014)

We would like to thank Drs. Sharifi and Auchus for their interest in our study, and appreciate the opportunity to address the issues they have raised ([1][1]). Their main point of contention concerns our ability to make informed comment on the contribution of the “5α-dione” pathway to DHT
The myth of the abortion trauma syndrome revisited
Authors: K. Dowling
Journal: JAMA (1993)

To the Editor.  —Dr Stotland contends that the abortion trauma syndrome is a myth 1 and states as her reason for this conclusion that she could find no references to this syndrome  the scientific   Having seen this entity in my own inner-city practice on several occasions, I was motivated to examine the literature. My brief research indicated that postabortion dysphoria is a documented entity in the medical and sociological literature, and is not confined, as Stotland would have it, to religious tracts and antiabortion publications.  Tamburrino et al 2 published an article that explored psychosocial factors, especially religion, in women identified as dysphoric 1 to 15 years after abortion. Another article 3 cites close to 100 references, including Psychiatric Sequelae of Therapeutic  4 and Postpartum and Postabortion Psychotic Reactions 5 among others.  Abortion is usually a significant life event. Regardless of where one stands on the ethics
BLOOD REACTION IN ETHYLENE AND NITROUS OXID ANESTHESIA
Authors: CHAUNCEY D. LEAKE
Journal: JAMA (1924)

The most noteworthy recent event in the development of anesthesia has been the revival of interest in ethylene as an anesthetic agent. This has occurred as a result of the experiments undertaken by Luckhardt and Carter,<sup>1</sup>which were independently confirmed by Brown,<sup>2</sup>and through the favorable clinical reports of the gas as a general anesthetic when used with oxygen, as noted by Luckhardt and Carter,<sup>3</sup>Luckhardt and Lewis,<sup>4</sup>and Lundy.<sup>5</sup> In comparing ethylene with ether as a general anesthetic, one is immediately struck with the more favorable postanesthetic condition under ethylene. Luckhardt and Lewis<sup>4</sup>report prompt recovery in every instance under ethylene-oxygen, and postoperative vomiting in only 30.2 per cent, of a large series of cases; while, in a comparable series under ether, the postoperative vomiting followed in 76.6 per cent, of the patients. So far, no untoward effects following ethylene have been reported.
Survey of distressing symptoms in dying patients and their families in hospital and the response to a symptom control team
Authors: J. M Hockley, R. Dunlop, R. J Davies
Journal: BMJ (1988)

The care given to 26 dying patients, and their families, being nursed in a hospital where there was no specific terminal care facility was studied. These patients were dying from both malignant and non-malignant disease. Anorexia, sleeplessness, coated or infected mouths, pain, and pressure sores were seen in half of the patients. Fear about caring for the patient at home and lack of information were the problems most frequently identified by the relatives. As a result of this study a multidisciplinary team specialising in symptom control and supportive care has been established. On average half of the total number of patients dying from cancer in the hospital are supported by the team. The number of complaints from relatives of dying patients has been drastically reduced since the team was formed.