tbuckley/cabot-search huggingface dataset:
A Wnt1 regulated Frizzled-1/β-Cateninsignaling pathway as a candidate regulatory circuit controlling mesencephalic dopaminergic neuron-astrocyte crosstalk: Therapeutical relevance for neuron survival and neuroprotection
Authors: Francesca L'Episcopo, Maria F Serapide, Cataldo Tirolo, Nunzio Testa, Salvatore Caniglia, Maria C Morale, Stefano Pluchino, Bianca Marchetti
Journal: Molecular Neurodegeneration (2011)

Abstract Background Dopamine-synthesizing (dopaminergic, DA) neurons in the ventral midbrain (VM) constitute a pivotal neuronal population controlling motor behaviors, cognitive and affective brain functions, which generation critically relies on the activation of Wingless-type MMTV integration site (Wnt)/β-catenin pathway in their progenitors. In Parkinson's disease, DA cell bodies within the substantia nigra pars compacta (SNpc) progressively degenerate, with causes and mechanisms poorly understood. Emerging evidence suggests that Wnt signaling via Frizzled ( Fzd ) receptors may play a role in different degenerative states, but little is known about Wnt signaling in the adult midbrain. Using in vitro and in vivo model systems of DA degeneration, along with functional studies in both intact and SN lesioned mice, we herein highlight an intrinsic Wnt1/Fzd-1/β-catenin tone critically contributing to the survival and protection of adult midbrain DA neurons. Results In vitro experiments identifie Fzd-1 receptor expression at a mRNA and protein levels in dopamine transporter (DAT) expressing neurons, and demonstrate the ability of exogenous Wnt1 to exert robust neuroprotective effects against Caspase-3 activation, the loss of tyrosine hydroxylase-positive (TH + ) neurons and [ 3 H] dopamine uptake induced by different DA-specific insults, including serum and growth factor deprivation, 6-hydroxydopamine and MPTP/MPP + . Co-culture of DA neurons with midbrain astrocytes phenocopies Wnt1 neuroprotective effects, whereas RNA interference-mediated knockdown of Wnt1 in midbrain astrocytes markedly reduces astrocyte-induced TH + neuroprotection. Likewise, silencing β-catenin mRNA or knocking down Fzd-1 receptor expression in mesencephalic neurons counteract astrocyte-induced TH + neuroprotection. In vivo experiments document Fzd-1 co-localization with TH + neurons within the intact SNpc and blockade of Fzd/β-catenin signaling by unilateral infusion of a Fzd/β-catenin antagonist within the SN induces reactive astrocytosis and acutely inhibits TH + neuron survival in ipsilateral SNpc, an effect efficiently prevented by pharmacological activation of β-catenin signaling within the SNpc. Conclusion These results defining a novel Wnt1/Fzd-1/β-catenin astrocyte-DA autoprotective loop provide a new mechanistic inside into the regulation of pro-survival processes, with potentially relevant consequences for drug design or drug action in Parkinson's disease.
Insulin sensitivity, metabolic flexibility, and serum adiponectin concentration in women with anorexia nervosa
Authors: Monika Karczewska-Kupczewska, Marek Strączkowski, Agnieszka Adamska, Agnieszka Nikołajuk, Elżbieta Otziomek, Maria Górska, Irina Kowalska
Journal: Metabolism (2009)
Livedo, dementia, thrombocytopenia, and endotheliitis without antiphospholipid antibodies: Seronegative antiphospholipid-like syndrome
Authors: Arnaud Duval, Luc Darnige, François Glowacki, Marie-Christine Copin, Elisabeth Martin De Lassalle, Emmanuel Delaporte, Eric Auxenfants
Journal: Journal of the American Academy of Dermatology (2009)
Mass gatherings and respiratory disease
Authors: Talha Khan Burki
Journal: The Lancet Respiratory Medicine (2013)

In mid-October, 2013, about 3·5 million pilgrims are expected to descend on Mecca, Saudi Arabia, to perform Hajj. Under the strictures of Islam, the rite is obligatory for all able-bodied Muslims at least once in their lifetimes. Hajj is the world's largest annual mass gathering; last year saw more than 1·7 million pilgrims arrive from abroad.
Association between Vogt-Koyanagi-Harada Syndrome and HLA-DR1 and -DR4 in Hispanic Patients Living in Southern California
Authors: James M. Weisz, Gary N. Holland, Laurence N. Roer, Min S. Park, A. Joyce Yuge, Ramana S. Moorthy, David J. Forster, Narsing A. Rao, Paul I. Terasaki
Journal: Ophthalmology (1995)
Erythema gyratum repens with pulmonary tuberculosis
Authors: P.V. BARBER, L. DOYLE, D.M. VICKERS, H. HUBBARD
Journal: British Journal of Dermatology (2006)

A 63-year-old man presented with erythema gyratum repens of 7 months'duration. A cavitating mass at the right lung apex was resected and proved to be tuberculous. Following the resection, the skin lesions cleared within a few days. Erythema gyratum repens has not previously been described in association with non-malignant visceral pathology. The pathogenesis remains obscure but cannot be related specifically to a response to tumour cells or their products in view of the association reported here. The condition bears no resemblance to any known tuberculide.
THE SIGNIFICANCE OF REFLEX ACTION IN COLOUR VISION
Authors: F. Allen
Journal: BMJ (1930)

_~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~E IA ORA relroperitoneal, bulging forwards on the mesial aspect of the descending colon; the transverse colon and the splenic flexure were above it.The great omentum was adherent across the front of it to the desceniding colon.The liver, spleen, and otlher viscera were niormial.A vertical incision was made through tlle peri- toneum on the outer side of the descending colon, and the tumour was shelled out and removed.It contained five pints of clear, watery liquid, and was the cvstic remains of the kidney.There was no recognizable renal tissue in it, butt the ureter issued from Its inner aspect at tlle lower point of trisection.The condition was one of valve ureter; there was no constriction by any abnormal vessel.The ureter itself was small in size.Three large renal vessels had to be tied and divided.The other kidniey was larger than usual, buit otlherwise normal.The paticnt made a good recovery.CASE V.-Hydronephrosis due to Valve Ureter; Urctcroplcisty; Recovery.A very stout married woman, aged 64, was admitted to Guy's Hospital on January 24th, 1928.In 1906 hysterectomy for fibroids was performed.Sinice 1914 slhe had had nutimerous attacks of severe pain in the right flank, below the costal margin, passing throuighl to the back, below the last rib.For years these attacks were thouglht to be due to gall-stonies.There was no history of jaunidice, or of anything wrong with the urine or urination.In October, 1927, a bad attack developed, with hiah fever annd " a swelling filling up nearly all the rigi-ht flank, which was evidently a hydronephrosis."Tlle symptoms graduially abated,
Primary gastric lymphoma in clinical practice 1973-1992.
Authors: A F Muller, A Maloney, D Jenkins, F Dowling, P Smith, E M Bessell, P J Toghill
Journal: Gut (1995)

This study assessed the presentation, treatment, and prognosis of primary gastric lymphoma in general hospital practice and its relation to infection with Helicobacter pylori. The number of patients that would on the current recommendations have been suitable for H pylori eradication therapy was also examined. All lymphomas were graded according to a standard classification of gut lymphoma into high and low grade disease. Forty five patients (mean age 65 years) were identified. The overall five year survival was 40% with a trend in favour of an improved prognosis for low grade and stage I disease. H pylori was present in 80%. Only one of 18 patients with a low grade mucosa associated lymphoid tissue tumour had mucosal disease alone, which responded to omeprazole and amoxycillin. All other patients had bulk disease. These patients were treated by surgery, chemotherapy or radiotherapy or a combination of these treatments. In district hospital practice, most cases of primary gastric lymphoma have bulk disease at presentation. Even in patients with low grade gastric lymphoma on histological examination, many on the current evidence would not be suitable for anti-H pylori therapy alone.
Modern Multidisciplinary Perioperative Management of Rectal Cancer
Authors: Mariana Berho, Rahul Narang, Julie Ann M. Van Koughnett, Steven D. Wexner
Journal: JAMA Surgery (2015)

<h3>Importance</h3> The management of care for rectal cancer has undergone many changes and improvements in recent decades. A multidisciplinary approach to this complex disease is essential to ensure high-quality treatment and outcomes. <h3>Objective</h3> To present a current, evidence-based approach to the multidisciplinary team management of rectal cancer with a review of the diagnosis, staging, and treatment of the disease by radiologists, oncologists, surgeons, and pathologists. <h3>Evidence Review</h3> The literature review was conducted through online searches of MEDLINE and PubMed. Articles published between January 1, 2000, and June 2014 and pertaining to staging modalities, surgical approaches, pathologic assessment, and medical treatments of rectal cancer were considered. All studies were reviewed, with preferential inclusion of larger or randomized trials. The review focused on changing paradigms and current controversies in rectal cancer management. <h3>Findings</h3> A multidisciplinary approach to the patient with rectal cancer includes many health care professionals. Although treatments continue to evolve and improve, clear evidence-based principles have been well studied. The important roles of various specialists must be acknowledged and utilized. Within each role, new and emerging treatment approaches require critical review by experts in their fields. <h3>Conclusions and Relevance</h3> Many new technologies and treatment options will continue to advance the treatment of rectal cancer, further emphasizing the need for a multidisciplinary approach to achieve optimal care.
Gastroscopic follow up of pernicious anaemia patients.
Authors: S M Sjoblom, P Sipponen, H Jarvinen
Journal: Gut (1993)

To assess the value of gastroscopic cancer surveillance of patients with pernicious anaemia, 56 patients were re-endoscoped and biopsied after three years. In addition, changes in the density of fundic mucosal endocrine cells were evaluated morphometrically. Two cases (3.6%) of early gastric cancer and two cases of small gastric carcinoid tumours (3.6%) were detected in addition to the five carcinoids that had been found at the initial endoscopic screening. Nodular argyrophil cell hyperplasia and morphometric density of argyrophil cells were not stable phenomena: nodular hyperplasias regressed in five patients, remained similar in six, and progressed to a small carcinoid tumour in one. Serum gastrin concentrations did not correlate well with changes in the endocrine cell density. Regular endoscopic surveillance for gastric cancer may be beneficial and realistic in young patients with pernicious anaemia while the importance of fundic endocrine cell hyperplasia and that of small gastric carcinoids need further study.
Psychiatric Treatment Strategies for Patients at Risk of Dying Suddenly
Authors: Brian Baker, Paul Dorian, Nadia Woloshyn, Shahe Kazarian, Caroline Lanphier
Journal: Psychotherapy and Psychosomatics (1991)

This paper outlines the development of psychiatric treatment approaches to certain patients with life-threatening ventricular arrhythmias which may affect outcome, both psychologial and, at times, medical. Three case sketches which illustrate psychiatric management strategies are presented. One case history indicates how lack of adherence to such treatment contributed to a negative outcome. Emphasis is placed on an integrated approach to psychiatric treatment which is individualized for each patient. The importance of close liaison with cardiologist, selective psychotherapy, stress management skills and family involvement is highlighted.
Pain Relief in Hospital: the More Widespread Use of Nitrous Oxide
Authors: P. J. F. Baskett, J. A. Bennett
Journal: BMJ (1971)

A trial was conducted of Entonox for pain relief in minor, but painful, procedures which are conducted in wards, accident centres, and radiological units. The gas was self-administered by the patient using a demand apparatus. The administration was supervised by qualified nurses, specially trained in the properties of Entonox and the inhalational unit. The results confirm that the gas is safe in the hands of these personnel. Gratifying pain relief occurred in most patients with almost complete freedom from undesirable side effects. It is suggested that patient comfort in hospital can be considerably improved by utilizing this method of analgesia to the full.
Overexpression of Transforming Growth Factor-β1 Stabilizes Already-Formed Aortic Aneurysms
Authors: Jianping Dai, Franck Losy, Anne-Marie Guinault, Carine Pages, Ignacio Anegon, Pascal Desgranges, Jean-Pierre Becquemin, Eric Allaire
Journal: Circulation (2005)

The cell response to transforming growth factor-beta1 (TGF-beta1), a multipotent cytokine with healing potential, varies according to tissue context. We have evaluated the ability of TGF-beta1 overexpression by endovascular gene therapy to stabilize abdominal aortic aneurysms (AAAs) already injured by inflammation and proteolysis.Active TGF-beta1 overexpression was obtained in already-developed experimental AAAs in rats after endovascular delivery of an adenoviral construct encoding for a mutated form of active simian TGF-beta1 and in an explant model using human atherosclerotic AAA fragments incubated with recombinant active TGF-beta1. Transient exogenous TGF-beta1 overexpression by endovascular gene delivery was followed by induction of endogenous rat TGF-beta1. Overexpression of active TGF-beta1 in experimental AAAs was associated with diameter stabilization, preservation of medial elastin, decreased infiltration of monocyte-macrophages and T lymphocytes, and a decrease in matrix metalloproteinase-2 and -9, which was also observed in the explant model, in both thrombus and wall. In parallel with downregulation of the destructive process, active TGF-beta1 overexpression triggered endoluminal reconstruction, replacing the thrombus by a vascular smooth muscle cell-, collagen-, and elastin-rich intima.Local TGF-beta1 self-induction after transient exogenous overexpression reprograms dilated aortas altered by inflammation and proteolysis and restores their ability to withstand arterial pressure without further dilation. This first demonstration of stabilization of expanding AAAs by delivery of a single multipotent self-promoting gene supports the view that endovascular gene therapy should be considered for treatment of aneurysms.
Cross-talk between iron homeostasis and intestinal inflammation
Authors: Bobby Cherayil
Journal: Gut Microbes (2010)

Recent publications from my laboratory have highlighted the important influence of altered iron homeostasis on the inflammatory response to intestinal bacteria. Here, I provide commentary on one of those papers, "Selective modulation of TLR4-activated inflammatory responses by altered iron homeostasis in mice", which was published in the Journal of Clinical Investigation in November, 2009. It describes experiments that point to a previously unappreciated role for intracellular iron in the regulation of Toll-like receptor 4 signaling, and also demonstrates the potential therapeutic application of this information in a novel anti-inflammatory strategy based on manipulating iron balance. Our findings indicate that further investigation of the cross-talk between iron homeostasis and inflammation will yield new insights into the pathogenesis of chronic inflammatory diseases and may suggest new treatment approaches for these conditions.
Enhanced intestinal absorption of an RGD peptide from water-in-oil microemulsions of different composition and particle size
Authors: Panayiotis P. Constantinides, Cindy M. Lancaster, Joseph Marcello, David C. Chiossone, Donald Orner, Ismael Hidalgo, Philip L. Smith, Ani B. Sarkahian, Seang H. Yiv, Albert J. Owen
Journal: Journal of Controlled Release (1995)
THE DERMATOLOGIST-SYPHILOLOGIST IN THE UNITED STATES
Authors: J. E. LANE
Journal: JAMA (1925)

The question, Why should the dermatologist be supposed to have special qualifications as a syphilologist? appears to be the approved form for the expression of the opinion that, in the enthusiasm for reorganizations and new starts which possesses a part of the medical world, the specialties of dermatology and syphilology, formerly supposed to be indissolubly bound together... in a union profitable to the progress of science, should be divorced, and a new type of syphilologist created.  Is the proposed change needful or likely to be advantageous to the future welfare of medicine?  In this country, as in continental Europe, the dermatologist has been a syphilologist since these branches of medicine developed into specialties. This is not for the reason, which some pretend to believe, that the dermatologist considers syphilis to be chiefly a disease of the skin; for he has always held, with Auspitz, that the skin is a Janus
PBC: an infectious disease?
Authors: G H HAYDON
Journal: Gut (2000)

Ninety general practitioners responded to a questionnaire about the role of radiology in patients with low back pain. Their clinical indications for requesting radiographs were mostly in agreement with the opinions of radiologists, but nearly 80% requested investigations for their own or patients9 reassurance. Understanding of the terms used by radiologists was good, although 25% thought that acute disc prolapse could be demonstrated on plain films. Previous training in radiology did not seem to influence knowledge. When general practitioners understood radiological terms they had clear therapeutic and specialist referral preferences. Poorly understood terms and those with which they were familiar but unclear about the implications for management were also identified.
Enhanced Organic Dust Induced Airway Inflammation in Protein Kinase C Epsilon Deficient Mice is Associated with Dysregulation of Nitric Oxide
Authors: J.A. Poole, A. Gleason, C. Bauer, W.W. West, D.J. Romberger, T.A. Wyatt
Journal: Journal of Allergy and Clinical Immunology (2012)
Mizspellin and Medline
Authors: J. G Ray, M. J Vermeulen
Journal: BMJ (1996)

handwriting of non-doctors.The mean score in our study was 7.1 out of a possible 13 points, indicating that handwriting among the average subject, whether a doctor or not, lies somewhere between the two middle samples in fig 1.In medical circumstances, where the stakes are high, writing of this mediocre quality may be unacceptable.If average handwriting is not acceptably safe or clear in medical care then we must seek ways either to "error proof" written communication or to reduce reliance on it.In the short run increasing individual's awareness and motivation may produce some minor gains.In the longer run, however, it may be more helpful to regard legibility as a systemic problem, not a personal one.Better physical designs, for example, might make it easier to write legibly.However, when the stakes are highest, safety may require not improving writing, but replacing it.We have shown, in a study with an artificial task and high inter-rater reliability, that doctors have handwrit- ing no worse than that of a comparison group of other healthcare personnel, and much better than that of healthcare executives.These findings in no way contradict lore and literature about the costs and hazards of poor writing in prescriptions and medical records, but they do refocus the problem.Illegibility in medical care may have less to do with "bad" (that is, exceptionally bad) handwriting among doctors than with handwriting in general as a form of communication.More help may be found in computerisation 8 and other systemic inno- vations than in pointing the finger at a profession whose members, on the whole, write with an average hand.
Pannexin-1-Mediated Recognition of Bacterial Molecules Activates the Cryopyrin Inflammasome Independent of Toll-like Receptor Signaling
Authors: Thirumala-Devi Kanneganti, Mohamed Lamkanfi, Yun-Gi Kim, Grace Chen, Jong-Hwan Park, Luigi Franchi, Peter Vandenabeele, Gabriel Núñez
Journal: Immunity (2007)
Single-Shot, Multicycle Suicide Gene Therapy by Replication-Competent Retrovirus Vectors Achieves Long-Term Survival Benefit in Experimental Glioma
Authors: Chien-Kuo Tai, Wei Jun Wang, Thomas C. Chen, Noriyuki Kasahara
Journal: Molecular Therapy (2005)

Achieving therapeutically efficacious levels of gene transfer in tumors has been a major obstacle for cancer gene therapy using replication-defective virus vectors. Recently, replicating viruses have emerged as attractive tools for cancer therapy, but generally achieve only transitory tumor regression. In contrast to other replicating virus systems, transduction by replication-competent retrovirus (RCR) vectors is efficient, tumor-selective, and persistent. Correlating with its efficient replicative spread, RCR vector expressing the yeast cytosine deaminase suicide gene exhibited remarkably enhanced cytotoxicity in vitro after administration of the prodrug 5-fluorocytosine. In vivo, RCR vectors replicated throughout preestablished primary gliomas without spread to adjacent normal brain, resulting in profound tumor inhibition after a single injection of virus and single cycle of prodrug administration. Furthermore, stable integration of the replicating vector resulted in persistent infection that achieved complete transduction of ectopic glioma foci that had migrated away from the primary tumor site. Thus, efficient and stable integration of suicide genes represents a unique property of the RCR vector that achieved multiple cycles of synchronous cell killing upon repeated prodrug administration, resulting in chronic suppression of tumor growth and prolonged survival.
Evolution of Conformational Dynamics Determines the Conversion of a Promiscuous Generalist into a Specialist Enzyme
Authors: T. Zou, V. A. Risso, J. A. Gavira, J. M. Sanchez-Ruiz, S. B. Ozkan
Journal: Molecular Biology and Evolution (2014)

β-lactamases are produced by many modern bacteria as a mechanism of resistance toward β-lactam antibiotics, the most common antibiotics in use. β-lactamases, however, are ancient enzymes that originated billions of years ago. Recently, proteins corresponding to 2- to 3-Gy-old Precambrian nodes in the evolution of Class A β-lactamases have been prepared and shown to be moderately efficient promiscuous catalysts, able to degrade a variety of antibiotics with catalytic efficiency levels similar to those of an average modern enzyme. Remarkably, there are few structural differences (in particular at the active-site regions) between the resurrected enzymes and a penicillin-specialist modern β-lactamase. Here, we propose that the ancestral promiscuity originates from conformational dynamics. We investigate the differences in conformational dynamics of the ancient and extant β-lactamases through MD simulations and quantify the contribution of each position to functionally related dynamics through Dynamic Flexibility Index. The modern TEM-1 lactamase shows a comparatively rigid active-site region, likely reflecting adaptation for efficient degradation of a specific substrate (penicillin), whereas enhanced deformability at the active-site neighborhood in the ancestral resurrected proteins likely accounts for the binding and subsequent degradation of antibiotic molecules of different size and shape. Clustering of the conformational dynamics on the basis of Principal Component Analysis is in agreement with the functional divergence, as the ancient β-lactamases cluster together, separated from their modern descendant. Finally, our analysis leads to testable predictions, as sites of potential relevance for the evolution of dynamics are identified and mutations at those sites are expected to alter substrate-specificity.