tbuckley/cabot-search huggingface dataset:
SHP-2 Phosphatase Negatively Regulates the TRIF Adaptor Protein-Dependent Type I Interferon and Proinflammatory Cytokine Production
Authors: Huazhang An, Wei Zhao, Jin Hou, Yan Zhang, Yun Xie, Yuejuan Zheng, Hongmei Xu, Cheng Qian, Jun Zhou, Yizhi Yu, Shuxun Liu, Gensheng Feng, Xuetao Cao
Journal: Immunity (2006)
The House of Medical Education
Authors: John T. Flynn
Journal: JAMA (1965)

<h3>To the Editor:—</h3> The comments of Dr. Seymour Farber in the article "Greatest Challenge in Medicine Today" (<b>193</b>:432, 1965) leave the impression that a physician educated more than a few years ago is hopelessly out of date. Personally I am sure he does not mean this; but he implies that a physician's progressive experience throughout his lifetime, his judicious selection of medical reading material, and periodic attendance at refresher courses will fail to maintain him as a "modern physician." Perhaps this impression of rapid obsolescence is promoted in the minds of medical school researchers and educators by their contact with the frontiers of medical science, where the value of any one fact is subject to constant fluctuation. If much of the information passed on to medical students becomes obsolete within a very short time, should not medical educators give serious thought to the<i>character</i>of the intormation which they
MORPHOLOGICAL AND OTHER CHARACTERISTICS OF THE AGENT OF FELINE PNEUMONITIS GROWN IN THE ALLANTOIC CAVITY OF THE CHICK EMBRYO
Authors: Dorothy Hamre, Helen Rake, Geoffrey Rake
Journal: The Journal of Experimental Medicine (1947)

The agent of feline pneumonitis has been grown in the allantoic cavity for 50 serial passages. During this time the amount of agent in allantoic fluid increased about 100-fold. The titer of the agent in the allantoic fluid of the individual embryo reached a peak on the 5th day and then declined. Large inocula were required in order to obtain maximal titers. The toxic factor was present in suspensions of chorioallantoic membranes in allantoic fluid from heavily infected eggs, and could be neutralized by the specific antitoxin produced in rabbits by injection of toxin in yolk sac suspensions. Electron micrographs of the agent of feline pneumonitis grown in the allantoic cavity show that the elementary body is composed of a dense centrally located substance surrounded by a thinner material, part or all of which is the limiting membrane. Separation of these two portions of the body may be due partially or entirely to distortion during drying. The wrinkled surface of the elementary bodies is evidence that such distortion does occur. The average diameter of gold-shadowed bodies is 525 mµ.
Book: In the Blood: Sickle Cell Anemia and the Politics of Race
Authors: H. Saloojee
Journal: BMJ (1999)

Melbourne Tapper University of Pennsylvania Press, £21.50, pp 160 ISBN 0 8122 34715 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> “Race” is a concept that has occupied a prominent place in the American culture for centuries. In spite of being conceptually vague, the use of “race” in health research has a long and sometimes disturbing history. Currently, thousands of publications exist on black-white differences in behaviour and disease patterns. Most anthropologists have rejected the traditional Western notion of race—as bounded, identifiable biological groups—both as a research tool and as a valid representation of biological diversity Nevertheless, the racialisation of disease continues to be a pervasive practice, risking the … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
Skin Cancer in Heart Transplant Recipients : Risk Factor Analysis and Relevance of Immunosuppressive Therapy
Authors: A. L. P. Caforio, A. B. Fortina, S. Piaserico, M. Alaibac, F. Tona, G. Feltrin, E. Pompei, L. Testolin, A. Gambino, S. D. Volta, G. Thiene, D. Casarotto, A. Peserico
Journal: Circulation (2000)

The frequency of skin tumors of all types and specifically of squamous cell carcinoma (SCC) is increased in heart transplantation (HT), but the predisposing risk factors are controversial.We studied 300 patients (age 49+/-15 years, 258 men, mean follow-up 4.6 years, follow-up range 1 month to 12 years) who were receiving standard double (cyclosporin plus azathioprine) or triple (cyclosporin plus azathioprine plus prednisone) therapy. The first-year rejection score was calculated for endomyocardial biopsy samples (International Society for Heart and Lung Transplantation grade 0=0, 1A=1, 1B=2, 2=3, 3A=4, 3B=5, and 4=6) and used as an indirect marker of the level of immunosuppression. Multivariate analysis (Cox regression) included age at HT, sex, skin type, first-year rejection score, presence of warts and solar keratosis, lifetime sunlight exposure, and first-year cumulative dose of steroids. The incidence of skin tumors of all types increased from 15% after 5 years to 35% after 10 years after HT according to life-table analysis. Age at HT of >50 years (P:=0.03, RR=5.3), skin type II (P:=0.05, RR=2.6), rejection score of 19 (P:=0.003, RR=5.7), solar keratosis (P:=0.001, RR=6.9), and lifetime sunlight exposure of >30 000 hours (P:=0.0003, RR=7.6) were risk factors for SCC.Older age at HT, light skin type, solar keratosis, greater sunlight exposure, and high rejection score in the first year were independently associated with an increased risk of SCC. The progressive increase in cancer frequency during follow-up and the association with high rejection scores suggest that both the length and level of immunosuppression may be relevant. Because cumulative immunosuppressive load is cumbersome to calculate, a high rejection score in the first year may provide a useful predictor for patients at risk.
Atherogenesis: a postprandial phenomenon.
Authors: D B Zilversmit
Journal: Circulation (1979)

The hypothesis that plasma chylomicrons in persons who ingest a cholesterol-rich diet are atherogenic is evaluated. Evidence is presented that in humans, and experimental animals, chylomicron remnants as well as low-density lipoproteins are taken up by arterial cells. In persons who do not have familial hyperlipoproteinemia, atherogenesis may occur during the postprandial period. Research directions that may contribute to the evaluation of chylomicron remnants as a risk factor for atherogenesis are discussed. Lipoprotein studies after administration of a test meal containing fat and cholesterol are urgently needed.
Methadone maintenance in general practice: patients, workload, and outcomes
Authors: P Wilson, R Watson, G E Ralston
Journal: BMJ (1994)

<h3>Abstract</h3> <b>Objective</b>: To assess recruitment to and workload associated with methadone maintenance clinics in general practice; to investigate the characteristics of patients and outcomes associated with treatment. <b>Design</b>: Study of case notes. <b>Setting</b>: Methadone maintenance clinics run jointly by general practitioners and drug counsellors in two practices in Glasgow. <b>Participants</b>: 46 injecting drug users receiving methadone maintenance during an 18 month period, 31 of whom were recruited to clinic based methadone maintenance treatment and 15 of whom were already receiving methadone maintenance treatment from the general practitioners. Mean (SD) age of patients entering treatment was 29.6 (5.5) years; 29 were male. They had been injecting opiates for a mean 9.9 (5.1) years, and most had a concurrent history of benzodiazepine misuse. Average reported daily intake of heroin was approximately 0.75 g. Participants in treatment had high levels of preexisting morbidity, and most stated that they committed crime daily. <b>Results</b>: 2232 patient weeks of treatment were studied. Mean duration of treatment during the study period was 50.7 (21.1) weeks and retention in treatment at 26 weeks was 83%. No evidence of illicit opiate use was obtained at an average of 78% of patients9 consultations where methadone had been prescribed in the previous week; for opiate injection the corresponding figure was 86%. <b>Conclusions</b>: Providing methadone maintenance in general practice is feasible. Although costs are considerable, the reduction in drug use, especially of intravenous opiates, is encouraging. Attending clinics also allows this population, in which morbidity is considerable, to receive other health care.
517. Type 1 Rep52 Is Superior to Authentic Rep52 for Producing Recombinant Adeno-Associated Virus Type 5 in Insect Cells
Authors: Masashi Urabe, Takayo Nakakura, Hiroaki Mizukami, Akihiro Kume, Robert M. Kotin, Keiya Ozawa
Journal: Molecular Therapy (2005)

Top of pageAbstract
The recently described method for producing recombinant adeno-associated virus (rAAV) type 2 in insect cells facilitates scale-up by using suspension cell cultures and baculovirus expression vectors (Hum Gene Ther 13:1935-1943, 2002). AAV5 is one of the most divergent dependovirus characterized and has been shown to utilize different receptors than AAV2 for example, and has demonstrated different tissue tropism from other serotype rAAVs. In addition to vectors derived from serotype 2, other serotypes constitute a vector set from which an optimal one can be selected for specific applications. Thus, we established a method to generate rAAV5 in insect cells. The current process requires triple infection with recombinant baculoviruses that provide the following: 1. AAV structural proteins that form the virus capsid (VP 1, 2, 3); 2. two of the AAV non-structural proteins for replication and encapsidation (Rep 78 and Rep 52); and 3. the AAV vector DNA which contain the gene of interest flanked by the AAV origins of replication (ITRs). Compared to other rAAV serotypes produced in insect cells, the rAAV5 yield per cell was substantially lower and we tested some modifications of the system. The initial Rep baculovirus drove type 5 Rep72 expression with a truncated promoter for the immediate-early 1 gene of Orgyia pseudotsugata nuclear polyhedrosis virus. The titers of the Rep baculovirus were relatively lower than others. We constructed Rep baculoviruses with a series of truncated p10 promoters for Rep78 and selected one that could produce rAAV5 at a high titer and propagate well. Rep52 or small Rep protein packages AAV genome into preformed empty capsids. We examined Rep52 of other serotypes, 1, 2, 3, 4 for generation of rAAV5 particles. The titer of rAAV5-GFP produced with type 1, 2, 3, or 4 small Rep was 56,000|[plusmn]|3,200, 41,000|[plusmn]|18,900, 42,000|[plusmn]|7,300, or 39,000|[plusmn]|3,500 particles per Sf9 cell while rAAV5-GFP produced by authentic Rep52 was 13,500|[plusmn]|3,200. The rAAV5-GFP produced with either serotype small Rep has an equal ratio of nucleic acid to capsid protein assessed by real-time PCR quantification and silver staining of purified rAAV5 particles. Also, rAAV5-GFP produced with either combination of large and small Rep proteins, transduced the simian Cos cell line with similar efficiency. The analysis by cesium density gradient of insect-cell lysates indicated that approximately 50% of all capsids contained the vector genome. These results indicate that heteroserotypic small Rep polypeptide is able to substitute for AAV5 small Rep and package AAV vector genome with type 5 in Sf9 cells and the new Rep baculovirus expressing type 5 Rep78 under the control of a truncated p10 promoter and type 1 Rep52 will contribute to the development of more efficient production of rAAV5 in insect cells.
Prolonged use of opioids after surgery
Authors: C. Duale
Journal: BMJ (2014)

Surgeons, anaesthetists, and primary care doctors can all help patients avoid it

In a linked paper (doi:10.1136/bmj.g1251), Clarke and colleagues present the results of a large retrospective cohort study conducted in Canada in 39 140 patients aged 66 or more who underwent major elective surgery and had never taken opioids before the procedure.1 Nearly half of the patients were discharged from hospital with an opioid prescription, illustrating that anaesthetists and surgeons no longer hesitate to use major analgesics beyond the immediate postoperative period. Although this trend has a positive effect on patient comfort and rehabilitation, concern has been raised by another important result from this study—that 3.1% of the patients were still taking opioids more than 90 days after surgery. Similarly, a 7.7% rate of opioid prescription has been reported at one year after low risk day surgery,2 and a follow-up study recently showed that 15% of women started or increased their purchase of analgesics after hysterectomy for benign disease.3 The medical profession therefore needs to ask whether long term opioid use is a real …
Familial Idiopathic Methaemoglobinaemia: Treatment with Ascorbic Acid
Authors: J. Deeny, E. T. Murdock, J. J. Rogan
Journal: BMJ (1943)

FAMILIAL IDIOPATHIC METHAEMOGLOBINAEMIA MEDBRTIRNAL 721with the following results.The figures indicate survivors after 30 hours.Test Dose Control
A Nosocomial Outbreak of Multidrug-Resistant Tuberculosis
Authors: Thomas A. Kenyon
Journal: Annals of Internal Medicine (1997)

Background: An outbreak of seven cases (in six patients and one health care worker, all of whom had AIDS) of multidrug-resistant tuberculosis occurred in a hospital in Chicago. The hospital had a respirator-fit testing program but no acid-fast bacilli isolation rooms. Objective: To identify risk factors for transmission of Mycobacterium tuberculosis. Design: Retrospective cohort study. Setting: Private hospital. Participants: Patients and health care workers exposed to M. tuberculosis. Measurements: Analysis of M. tuberculosis isolates, tuberculin skin testing, assessment of exposure, and assessment of participant characteristics. Results: All seven M. tuberculosis isolates had matching DNA fingerprints. Of patients exposed to M. tuberculosis, those who developed tuberculosis had lower CD4+ T-lymphocyte counts (P = 0.02) and were more likely to be ambulatory (P = 0.03) than those who did not. Of 74 exposed health care workers, the 11 (15%) who had conversion on tuberculin skin testing were no more likely than those who did not have conversion to report that they always wore a respirator with a high-efficiency particulate air filter. Conclusions: Transmission of M. tuberculosis occurred in a hospital that did not have recommended isolation rooms. A respirator-fit testing program did not protect health care workers in this setting.
REMOVABLE INTERNAL FIXATION IN FRACTURES
Authors: W. B. CARRELL
Journal: JAMA (1931)

An analysis of the fracture problem by committees making careful surveys in large groups of cases, during the past few years, has served to establish certain definite principles that must be followed, though methods for carrying out these principles will differ with surgeons according to their training and equipment. The final result, a return to function, may be equally good with widely variant methods. In appraising a fracture one must see more than a broken bone. The ultimate goal, return to function, depends on the recovery of muscles and ligaments as well, for bones may unite in good position after rough handling, but the damage in soft tissue may be irreparable. A trained surgeon with the right conception of the problem will be able to reduce most fractures by manipulation or traction and direct the subsequent treatment for the patient's final recovery. It should therefore be the aim of the
Esophageal carcinoma metastatic to the patella. A case report
Authors: M. E. Ashby
Journal: JAMA (1976)

ANY type of patellar neoplasm, whether benign or malignant, or primary or secondary, is rare. Only 15 cases can be found in the literature, involving metastatic diseases to the patella. Primary sites in these cases were the breast, prostate, lung, lymphatic system, uterine cervix, melanin-forming cells, and esophagus.<sup>1-6</sup> The following case represents only the second report, to our knowledge, of metastatic esophageal carcinoma to the patella in the literature. <h3>Report of a Case</h3> A 55-year-old man was admitted to the hospital in September 1974, with a fourmonth history of progressive dysphagia and weight loss. A barium-swallow examination and esophagoscopy showed a 10-cm esophageal mass, which proved to be epidermoid carcinoma on biopsy. In October 1974, the patient had an esophagectomy and esophagogastrostomy. He received radiation therapy postoperatively and was discharged to outpatient follow-up in November 1974 in good condition. In April 1975, the patient visited the emergency room of
Dealing with extracontractual referrals.
Authors: J D Williamson
Journal: BMJ (1991)

To describe the mechanism established by Richmond, Twickenham, and Roehampton Health Authority to manage extracontractual referral requests made on behalf of its resident population and to examine its working in the first three months of the new arrangements.Description of the procedures for managing extracontractual referrals and the decisions made on requests submitted to the district health authority between 1 April and 30 June 1991.235 requests were submitted, 79 for emergency care. 156 requests were clearly for elective treatments and, of these, 61 were ultimately refused, 20 because the district health authority was not liable to pay. Of the remaining 41, 17 were appealed successfully and three unsuccessfullly. More than half of the elective extracontractual referrals correctly submitted were to either orthopaedics, general surgery, oral surgery, gynaecology, or plastic surgery. Overall, the district health authority approved three quarters of the requests for which it would be financially liable; this was the predicted workload for the period.The management of extracontractual referral requests is complex and time consuming for clinicians and managers alike. Patient choice is clearly being limited to some extent, but this is necessary if the number of requests is not to exceed the levels on which funding is based.
Unusual Clinical and Molecular-Pathological Profile of Gerstmann-Sträussler-Scheinker Disease Associated With a Novel<i>PRNP</i>Mutation (V176G)
Authors: Marion Simpson, Vanessa Johanssen, Alison Boyd, Genevieve Klug, Colin L. Masters, Qiao-Xin Li, Roger Pamphlett, Catriona McLean, Victoria Lewis, Steven J. Collins
Journal: JAMA Neurology (2013)

Here we describe the unusual clinical and molecular-neuropathological profile of a case of Gerstmann-Sträussler-Scheinker disease associated with a novel prion protein (PRNP) gene mutation.This case report from the Australian National Creutzfeldt-Jakob Disease Registry concerns a 61-year-old British-born woman with no history of neurodegenerative disorder in first-degree relatives. Rapidly progressive dementia, altered behavior, and cerebellar ataxia dominated the clinical picture in the period immediately following minor elective surgery, with death 1 month later in an akinetic-mute state. Brain histopathological examination revealed neuronal loss, scant foci of spongiform change, and diffuse multicentric amyloid plaques, selectively immunoreactive for prion protein, within the cerebral and cerebellar cortices and deep gray matter. Tau immune-reactive neurofibrillary tangles and neuritic threads were present in the cerebral cortex. PRNP sequencing demonstrated a valine to glycine mutation at codon 176, with valine homozygosity at polymorphic codon 129. Western-blot analysis of frozen brain tissue displayed a nonclassic protease-resistant prion protein banding pattern, with a prominent approximately 8-kDa protease-resistant fragment.Reported is a proband with a novel PRNP mutation associated with neuropathologically confirmed Gerstmann-Sträussler-Scheinker disease displaying a somewhat unusual constellation of clinicopathological features, which overall subserve to further broaden an already diverse phenotypic spectrum.
P473 BACTERIAL INFECTIONS IN CIRRHOTIC PATIENTS: RISK FACTORS AND RATE OF FAILURE OF THE EMPIRICAL ANTIBIOTIC THERAPY
Authors: V. Di Gregorio, C. Lucidi, V. Giannelli, B. Lattanzi, M. Giusto, G. Iacovone, M. Venditti, O. Riggio, M. Merli
Journal: Journal of Hepatology (2014)
Abstract 1610: Curcumin inhibition of the functional interaction between integrin α6β4 and the epidermal growth factor receptor
Authors: Young Hwa Soung, Jun Chung
Journal: Cancer Research (2012)

Abstract The functional interaction between integrin α6β4 and growth factor receptors has been implicated in key signaling pathways important for cancer cell function. However, few attempts have been made to selectively target this interaction for therapeutic intervention. Previous studies showed that curcumin, a yellow pigment isolated from tumeric, inhibits integrin α6β4 signaling important for breast carcinoma cell motility and invasion, but the mechanism is not currently known. To address this issue, we tested the hypothesis that curcumin inhibits the functional interaction between α6β4 and the epidermal growth factor receptor (EGFR). In this study, we found that curcumin disrupts functional and physical interactions between α6β4 and EGFR, and blocks α6β4/EGFR dependent functions of carcinoma cells expressing the signaling competent form of α6β4. We further demonstrated that curcumin inhibits EGF dependent mobilization of α6β4 from hemidesmosomes to the leading edges of migrating cells such as lammelipodia and filopodia, and thereby prevents α6β4 distribution to lipid rafts where functional interactions between α6β4 and EGFR occur. These data suggest a novel paradigm in which curcumin inhibits α6β4 signaling and functions by altering intracellular localization of α6β4, thus preventing its association with signaling receptors such as EGFR. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1610. doi:1538-7445.AM2012-1610
Economic Evaluations of Medical Care Interventions for Cancer Patients: How, Why, and What Does it Mean?
Authors: Ya-Chen Tina Shih, Michael T. Halpern
Journal: CA A Cancer Journal for Clinicians (2008)

While the past decade has seen the development of multiple new interventions to diagnose and treat cancer, as well as to improve the quality of life for cancer patients, many of these interventions have substantial costs. This has resulted in increased scrutiny of the costs of care for cancer, as well as the costs relative to the benefits for cancer treatments. It is important for oncologists and other members of the cancer community to consider and understand how economic evaluations of cancer interventions are performed and to be able to use and critique these evaluations. This review discusses the components, main types, and analytic issues of health economic evaluations using studies of cancer interventions as examples. We also highlight limitations of these economic evaluations and discuss why members of the cancer community should care about economic analyses.
Effects of osmoreceptor stimulation on human duodenal motor activity.
Authors: D G Thompson, D L Wingate
Journal: Gut (1988)

The motor responses of the human duodenum to saline solutions of varying osmolality were examined in order to investigate the possible role played by the upper intestine in the control of gastric efflux of hyperosmolar material. During fasting, delivery of the solutions into the duodenum increased duodenal motor activity and intraduodenal pressure, the magnitude of the response increasing with osmolality. At the highest osmolalities, a regular duodenal motor pattern was induced in some individuals which was indistinguishable from fasting phase III activity. After feeding, hyperosmolar saline again increased motor activity. In addition, the transit of an intraduodenal marker to the caecum was accelerated. These findings support the concept that the duodenum is both sensitive and responsive to its intraluminal content. The motor responses additionally appear to function to clear excessively stimulating intraluminal material from the duodenal lumen and may also contribute to the 'postpyloric' resistance which is known to exert control of normal gastric emptying.