tbuckley/cabot-search huggingface dataset:
Non-angiogenic FGF-2 protects the ischemic heart from injury, in the presence or absence of reperfusion
Authors: Z Jiang
Journal: Cardiovascular Research (2004)

Objective: Fibroblast growth factor-2 (FGF-2), given during ischemia or during reperfusion of the ischemic heart is cardioprotective, but its mitogenic activity may limit possible clinical applications. We have tested the cardioprotective potential of a non-mitogenic FGF-2 mutant (S117A) that no longer activates casein kinase 2 (CK2) in both acute and long-term studies. Methods and results: To test effects during reperfusion, the ex vivo rat heart, subjected to 30 min of global ischemia and 60 min of reperfusion was used. S117A FGF-2 administered during reperfusion protected against myocardial contractile dysfunction, activated protein kinase C and decreased the release of cytochrome C in the cytosol. To study effects on ischemic myocytes in the absence of reperfusion, myocardial infarction (MI) was induced in the rat model by irreversible left coronary ligation. S117A-, wild type (wt)-FGF-2 or saline, were administered by intramyocardial injection into the ischemic ventricular wall. One day later, infarct size (assessed by tetrazolium staining), and plasma cardiac troponin T levels (assessed by Western blotting) were significantly decreased in the S117A FGF-2-, compared to the saline-treated group. Systolic pressure, rates of contraction and relaxation and developed pressure, assessed in the Langendorff mode, were significantly improved in the S117-FGF-2 group. Improved ejection fraction and fractional shortening in the S117A-treated group were maintained up to, but not beyond, 7 days post-MI. In comparison, improvements were maintained in the wt-FGF-2-treated group at least up to 6 weeks post-MI. At 6 weeks post-MI, small vessel density (assessed by immunofluorescence-based detection) in the scar bordering viable myocardium was similar between S117A-FGF-2- and saline-treated hearts, but significantly increased in the wt-FGF-2-treated group. This was accompanied by increased coronary flow in the wt-, but not S117A-FGF-2-treated hearts, compared to controls. Conclusion: The ability of FGF-2, administered during ischemia or during reperfusion, to protect the myocardium acutely from tissue loss and dysfunction is independent of its potential for CK2 activation and angiogenesis. Non-angiogenic S117A-FGF-2 may be considered in therapies aiming for acute prevention of reperfusion-associated pathologies, especially in cases where use of mitogens is counter-indicated.
Government agrees to screen war veterans for uranium exposure
Authors: O. Dyer
Journal: BMJ (2001)

Treatment with NGF causes long-term cultures of oligodendrocytes to die via a yet undefined mechanism mediated by the p75 neurotrophin receptor. The p75 receptor belongs to the TNF receptor superfamily of molecules, which includes Fas and p55 TNF receptors. The Fas and TNF receptors use adaptor molecules to recruit and activate caspase-8 to the receptor. Using a combination of immunohistochemical and Western blotting assays, we have examined caspase activity during NGF-induced apoptosis. Interestingly, although caspase-1 [interleukin-1β-converting enzyme (ICE)], caspase-2, caspase-3, and caspase-8 were expressed in oligodendrocytes, only caspase-1, -2, and -3 were activated after NGF treatment, whereas caspase-8 was not. These data suggest that the mechanism of apoptosis by NGF through the p75 receptor is different from TNF and Fas-mediated killing. γ Radiation of oligodendrocytes also activated a similar subset of caspases as NGF, indicating that NGF-induced oligodendrocyte apoptosis uses a similar cell death execution mechanism as injury models. This consolidates a potential role of the p75 neurotrophin receptor during stress and inflammatory conditions.
Acute intermittent porphyria: characterization of a novel mutation in the structural gene for porphobilinogen deaminase. Demonstration of noncatalytic enzyme intermediates stabilized by bound substrate.
Authors: R J Desnick, L T Ostasiewicz, P A Tishler, P Mustajoki
Journal: Journal of Clinical Investigation (1985)

To investigate the molecular pathology in acute intermittent porphyria (AIP), the nature of the defective porphobilinogen (PBG)-deaminase was determined in erythrocyte lysates from 165 AIP heterozygotes from 92 unrelated families representing 20 different ethnic or demographic groups. Immunologic and physicokinetic studies revealed the occurrence of four classes of PBG-deaminase mutations. In the majority of families studied, the amount of immunoreactive enzyme protein corresponded to the amount of enzymatic activity, indicating the absence of cross-reacting immunologic material (CRIM) produced by the mutant allele. In 78 of these CRIM-negative families (designated type 1), the affected heterozygotes had half-normal PBG-deaminase activity. In three families (designated CRIM-negative type 2), symptomatic patients had increased urinary excretion of delta-aminolevulinic acid and PBG, and normal levels of erythrocyte PBG-deaminase activity. In contrast, noncatalytic, immunoreactive protein was expressed in heterozygotes from 11 families, about one-eighth of those studied, consistent with mutations in the structural gene for PBG-deaminase. Two types of CRIM-positive mutations were identified: the type 1 mutation had a CRIM/activity ratio of approximately 1.7 and a crossed-immunoelectrophoretic profile in which all the enzyme intermediates were increased, with the B or monopyrrole-enzyme intermediate predominant (B greater than A much greater than C congruent to D greater than E). The mutation altered both the kinetic and stability properties of the noncatalytic immunoreactive enzyme protein. The second CRIM-positive mutation, type 2, had markedly increased levels of noncatalytic immunoreactive protein (CRIM/activity ratio approximately 5.7). Crossed-immunoelectrophoresis revealed markedly increased amounts of the substrate-bound intermediates, B, C, D, and E (B greater than C greater than D greater than E much greater than A). The accumulation of these noncatalytic enzyme intermediates presumably resulted from the enhanced binding and/or defective release of substrate molecules. The conformation of these enzyme-substrate intermediates apparently rendered the complexes more resistant to intraerythrocyte proteolysis. These findings provide evidence for the presence of different allelic mutations in the structural gene for PBG-deaminase and document molecular genetic heterogeneity in AIP.
β-catenin blocks Kras-dependent reprogramming of acini into pancreatic cancer precursor lesions in mice
Authors: John P. Morris, David A. Cano, Shigeki Sekine, Sam C. Wang, Matthias Hebrok
Journal: Journal of Clinical Investigation (2010)

Cellular plasticity in adult organs is involved in both regeneration and carcinogenesis. WT mouse acinar cells rapidly regenerate following injury that mimics acute pancreatitis, a process characterized by transient reactivation of pathways involved in embryonic pancreatic development. In contrast, such injury promotes the development of pancreatic ductal adenocarcinoma (PDA) precursor lesions in mice expressing a constitutively active form of the GTPase, Kras, in the exocrine pancreas. The molecular environment that mediates acinar regeneration versus the development of PDA precursor lesions is poorly understood. Here, we used genetically engineered mice to demonstrate that mutant Kras promotes acinar-to-ductal metaplasia (ADM) and pancreatic cancer precursor lesion formation by blocking acinar regeneration following acute pancreatitis. Our results indicate that beta-catenin is required for efficient acinar regeneration. In addition, canonical beta-catenin signaling, a pathway known to regulate embryonic acinar development, is activated following acute pancreatitis. This regeneration-associated activation of beta-catenin signaling was not observed during the initiation of Kras-induced acinar-to-ductal reprogramming. Furthermore, stabilized beta-catenin signaling antagonized the ability of Kras to reprogram acini into PDA preneoplastic precursors. Therefore, these results suggest that beta-catenin signaling is a critical determinant of acinar plasticity and that it is inhibited during Kras-induced fate decisions that specify PDA precursors, highlighting the importance of temporal regulation of embryonic signaling pathways in the development of neoplastic cell fates.
Contact Dermatitis Caused by Saran Wrap
Authors: Raymond A. Osbourn
Journal: JAMA (1964)

RECENTLY, the use of thin plastic films as covering or occlusive dressings in therapy with ointments and creams, especially hydrocortisone derivatives, has been advocated for treatment of several dermatoses.<sup>1-3</sup>This form of therapy is often very beneficial and is becoming increasingly popular. Only a few complications have been reported from the use of such films. Among them were discomfort from perspiration under the film, a miliarialike eruption, and folliculitis.<sup>1,3</sup>Where hydrocortisone derivatives were used, atrophy has also been reported.<sup>4</sup> It is our purpose to report a rare complication, ie, contact dermatitis, from the use of a film ( Saran Wrap) itself. <h3>Report of a Case</h3> A 30-year-old white male consulted us on May 2, 1963, because of psoriasis involving his scalp, legs, and arms. According to his medical history, he had had intermittent attacks of psoriasis for many years. He had in the past been treated with aminopterin
The CME Doctor
Authors: Max Burger
Journal: JAMA (1994)

If you have ever had trouble keeping track of your continuing medical education (CME) credits for the AMA Physicians Recognition Award (PRA), this program should do the trick. Specifically designed for<i>Windows</i>, it requires little use of a manual because of its point-and-click, icon-driven program. It keeps a running total of accumulated CME hours and a subtotal by category 1 and category 2 of AMA PRA criteria. It sorts and indexes events by sponsor, topic, date, and category and can print the information in a format required by the AMA for its CME PRAs. <i>The CME Doctor</i>consists of a title page of commands, which can be clicked onto for recording a CME event, personalizing the program, viewing CME progress, viewing an index of CME, or receiving help with the program. The Personalize command sets up your name, address, and the beginning and end dates for the CME reporting period
Right ventricular volume determinations in 18 patients with pulmonary atresia and intact ventricular septum. Analysis of factors influencing right ventricular growth.
Authors: R G Patel, R M Freedom, C A Moes, K R Bloom, P M Olley, W G Williams, G A Trusler, R D Rowe
Journal: Circulation (1980)

Right ventricular growth was assessed angiocardiographically in 18 patients with pulmonary atresia, intact ventricular septum, and hypoplastic and hypertensive right ventricle. A variety of surgical procedures were performed. In only 12 patients (66.7%) was right ventricular-pulmonary artery continuity achieved (group 1). Nine of these 12 patients persisted with systemic or suprasystemic right ventricular pressures. Among the six patients in whom right ventricular-pulmonary artery continuity was not achieved (group 2), all maintained suprasystemic right ventricular pressures. Right ventricular growth was assessed in groups 1 and 2. The patients were also subdivided according to the qualitative degree of tricuspid regurgitation as determined angiocardiographically on right ventricular cineangiocardiograms at the preoperative catheter study. Right ventricular growth to normal levels as evidenced by change in right ventricular end-diastolic volume was rarely observed in group 2 patients. Among the four patients with severe tricuspid regurgitation and a large tricuspid valve, right ventricular growth to normal levels was achieved whether they were in group 1 or group 2. Right ventricular growth is thus predicated on numerous morphologic factors in these patients. However, reconstitution of right ventricular-pulmonary artery continuity and a nonobstructive tricuspid valve are probably two of the more important factors.
Pioneer GABA Cells Comprise a Subpopulation of Hub Neurons in the Developing Hippocampus
Authors: Michel Aimé Picardo, Philippe Guigue, Paolo Bonifazi, Renata Batista-Brito, Camille Allene, Alain Ribas, Gord Fishell, Agnès Baude, Rosa Cossart
Journal: Neuron (2011)
Funding is important for randomised trials of surgery
Authors: S. Bridgman, J. Elder, R. Gray, R. Lilford
Journal: BMJ (1997)

Editor—In their editorial on removing bias in surgical trials A G Johnson and J Michael Dixon mention the safety and efficacy register of new interventional procedures.1 We consider this register to be an encouraging start, but it is not a substitute for randomised controlled trials of new surgical techniques.

The opportunity to participate in randomised controlled trials should be offered to all suitable patients because randomisation minimises bias and moderate bias may obscure or exaggerate moderate differences between treatments.2 Some …
Observing patients: Deaf wife
Authors: E. Besterman
Journal: BMJ (1999)

Years ago in my consulting room I was seeing an old patient for his regular six monthly review, and was pleased when my receptionist sent in his wife as I had never met any of his relatives. During the usual questioning I addressed odd remarks and questions to her which elicited no response. In his notes I then wrote “deaf wife.” After a physical examination, an electrocardiogram, and an x ray examination I bade him goodbye and noted that the wife remained seated. I inquired if she was not going to accompany her husband? She then spoke up to say, “I am not his wife, but your next patient. I was fascinated to see the whole procedure, but have one complaint. Next time could you provide a better male specimen, someone like Paul Newman?”
The Legacy of Soma Weiss
Authors: James V. Warren
Journal: New England Journal of Medicine (1972)

A generation of physicians will be startled by the reminder that Soma Weiss died on January 31, 1942, just 30 years ago, at the age of 43. He had been appointed as the Hersey Professor of the Theory and Practice of Physic at Harvard and Chief of Medicine at Peter Bent Brigham Hospital in 1939. In his short life-span, he left an impressive mark on American medicine. When his name is mentioned, some may think of carotid-sinus syncope, and others of beriberi or scleroderma heart disease. However, those close to him will remember him as an educator, although I do . . .
Editorial was wide of the mark
Authors: N. Peirce, S. Till, M. Wotherspoon, M. Stone
Journal: BMJ (2009)

<h3>Abstract</h3> Rainfall is rare in hyperarid deserts but, when it occurs, it triggers large biological responses which are considered to be essential for the long-term maintenance of biodiversity. In such environments, microbial communities have major roles in nutrient cycling, but their functional responses to short-lived resource opportunities are poorly understood. We used whole community metatranscriptomic data to demonstrate structured and sequential functional responses in desiccated desert soils to a simulated rainfall event over a seven-day time frame. Rapid transcriptional activation of Actinobacteria, Alpha-proteobacteria and phage transcripts was followed by a marked increase in protist and myxobacterial activity, before returning to the original state. In functional terms, motility systems were activated in the early phases, whereas competition-toxicity systems increased in parallel to the activity from predators and the drying of soils. The dispersal-predation dynamic was identified as a central driver of microbial community responses to watering. Carbon fixation mechanisms that were active under dry condition were rapidly down-regulated in wetted soils, and only reactivated on a return to a near-dry state, suggesting a reciprocal balance between carbon fixation and fixed-carbon acquisition processes. Water addition induced a general reduction in the transcription of stress response genes, most prominently HSP20, indicating that this chaperone is particularly important for life in desiccated ecosystems. Based on these data, we propose a rainfall response model for desert soil microbiomes.
Slow euthanasia? The deaths of psychogeriatric patients.
Authors: D Black, D Jolley
Journal: BMJ (1990)

Psychogeriatric services reach out to people who are suffering from psychiatric disorders which may persist until death and may bring forward death. It has been suggested that these services should aim at avoiding admitting patients for hospital care whose lives may be ended by the upset of admission or prolonged by inappropriate nursing and medical interventions. A review of the characteristics of patients dying during one year while under the care of a psychogeriatric service showed that one in three died as a psychogeriatric inpatient, the remainder dying at home or as inpatients in a general hospital. Those dying as psychogeriatric inpatients differed in their clinical and social characteristics from those dying elsewhere and it seemed unlikely that they could have been cared for humanely without the resources of the hospital ward. Psychogeriatric practice has many similarities to the work of hospices with other terminally ill patients, but the duration of the terminal illness and the needs arising from it are often more prolonged. Probably the management of dying among psychogeriatric patients will be improved if lessons learnt from other hospice practices are adopted.
Correlation between exhaled nitric oxide and dietary consumption of fats and antioxidants in children with asthma
Authors: Fabio Cardinale, Riccardina Tesse, Chiara Fucilli, Maria Sterpeta Loffredo, Gaia Iacoviello, Iolanda Chinellato, Lucio Armenio
Journal: Journal of Allergy and Clinical Immunology (2007)
Motor Examination of Peripheral Nerve Injuries
Authors: Fred Plum
Journal: JAMA (1961)

This small volume illustrates photographically methods of clinical testing for specific peripheral nerve function. In addition, pictures show the characteristic appearance of extremities after the commoner peripheral nerve injuries. Substitutions and "trick" movements which may mislead the inexperienced examiner are demonstrated. The descriptions are generally accurate (an exception is that the innervation of peroneus longus is given as the fourth and fifth sacral nerves on page 87), and the examining techniques are the accepted ones. Line diagrams show the maximal and minimal sensory losses to be expected with each nerve lesion as well as the motor distribution of the major nerve trunks in the extremities. The photography is not always clear, which is regrettable in a book that is chiefly a photographic presentation. There are no references or allusions to other than clinical methods of peripheral nerve testing. Inevitably, a book such as this invites comparison with other material available
Cardiomegaly and haemodynamics in rats with a transplantable growth hormone-secreting tumour
Authors: D. G PENNEY, J. C DUNBAR, M. S BAYLERIAN
Journal: Cardiovascular Research (1985)

Journal Article Cardiomegaly and haemodynamics in rats with a transplantable growth hormone-secreting tumour Get access DAVID G PENNEY, DAVID G PENNEY **Address for correspondence and reprint requests: David G Penney, PhD, Associate Professor, Department of Physiology, Wayne Stale University School of Medicine, 540 E. Canfield, Detroit, Ml 48201 USA. Search for other works by this author on: Oxford Academic PubMed Google Scholar JOSEPH C DUNBAR, JR, JOSEPH C DUNBAR, JR Search for other works by this author on: Oxford Academic PubMed Google Scholar MICHAEL S BAYLERIAN MICHAEL S BAYLERIAN Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 19, Issue 5, May 1985, Pages 270–277, https://doi.org/10.1093/cvr/19.5.270 Published: 01 May 1985
Endoscopic pancreatography in evaluating results of pancreatico-jejunostomy.
Authors: C Kugelberg, L Wehlin, B Arnesjo, U Tylen
Journal: Gut (1976)

It has been difficult, employing clinical methods, to establish whether pancreatico-enteric drainage shunts for chronic pancreatitis have remained patent and how the operation has affected the inflammatory changes and ductal pathological morphology. In an attempt objectively to evaluate postoperative results, 13 patients with two different types of pancreatico-jejunostomies were examined with endoscopic pancreatography. Progress of the inflammatory changes was noted to a varying degree in the majority of cases. In four patients subjected to longitudinal split of the pancreatic duct, shunt patency was evidenced. In the remaining nine patients with caudal pancreatico-jejunostomy, no contrast medium could be made to pass the shunts in six cases, whereas passage was clearly demonstrated in one and uncertain in two. All the patients reported clinical improvement after operation.
Toward a Comprehensive HIV Prevention Program for the CDC and the Nation
Authors: Donald P. Francis
Journal: JAMA (1992)

THE CENTERS for Disease Control (CDC), Atlanta, Ga, has a well-deserved reputation for making clear analyses of health problems and taking rapid action to improve the public's health. The CDC's success has been marked by its ability to keep science first. It has learned from experience that organizations that base their actions primarily on scientific findings rather than political considerations survive as effective entities, while those that do the opposite lose credibility and enter a spiral of decay. The CDC is known worldwide for its frankness and honesty, for its ability to scientifically assess the extent of a disease problem, evaluate the tools available to limit the damage it may cause, develop methods to apply those tools, and evaluate the effectiveness of their application. Despite its reputation, with the human immunodeficiency virus (HIV) epidemic, CDC has been soundly criticized for ineptness. Why is this? In search of an answer, I