tbuckley/cabot-search huggingface dataset:
A conditionally replicating HIV-based vector that stably expresses an antiviral shRNA against HIV-1 replication
Authors: Ellen M. Westerhout, Monique Vink, P.C. Joost Haasnoot, Atze T. Das, Ben Berkhout
Journal: Molecular Therapy (2006)

Human pathogenic viruses can be targeted by therapeutic strategies based on RNA interference. Whereas the administration of synthetic short interfering RNAs (siRNAs) may transiently inhibit viral replication, long-term inhibition may be achieved through stable intracellular expression of siRNAs or short hairpin RNAs (shRNAs). Both approaches face serious problems with delivery to the right cells in an infected individual. We explored the potential of a replicating HIV-based vector to deliver an antiviral shRNA cassette into HIV-1-susceptible target cells to block chronic HIV-1 infection. The vector is based on a doxycycline (dox)-dependent HIV-1 variant that we previously proposed as a conditional-live HIV-1 vaccine. With dox, this virus spreads efficiently to all HIV-susceptible cells. Subsequent dox withdrawal generates cells with a transcriptionally silent integrated provirus, but with an active shRNA expression cassette. Because the shRNA targets viral sequences that are removed from the vector construct, there is no self-targeting, yet there is specific shutdown of HIV-1 replication.
SilverPlatter MEDLINE Professional
Authors: Saty Satya-Murti
Journal: JAMA (1991)

We are a community of 30 physicians, engaged in family practice and various specialties. We admit to a 100-bed hospital. We draw patients from a 50-mile radius. Some of us consult for a nearby large state facility for the handicapped and for local industries. The nearest full medical library is at least 120 miles away. We wish to be well informed, and the academic Muse hasn't left some of us who wish to publish in peer-reviewed journals. On-line data access, now a well-established method of keeping up, is expensive even if one were to overcome the inhibitions that go with on-line "exposure." We were paying $1500 annually to display an asthenic collection of 15 core clinical journals that stayed pristine for two weeks on the shelves and were discarded at the end of the year for want of storage space. This was no way to keep up or to encourage
Factors in childhood as predictors of asthma in adult life
Authors: M. A Jenkins, J. L Hopper, G. Bowes, J. B Carlin, L. B Flander, G. G Giles
Journal: BMJ (1994)

<h3>Abstract</h3> <b>Objective</b>: To determine which factors measured in childhood predict asthma in adult life. <b>Design</b>: Prospective study over 25 years of a birth cohort initially studied at the age of 7. <b>Setting</b>: Tasmania, Australia. Subjects—1494 men and women surveyed in 1991-3 when aged 29 to 32 (75% of a random stratified sample from the 1968 Tasmanian asthma survey of children born in 1961 and at school in Tasmania). <b>Main outcome measures</b>: Self reported asthma or wheezy breathing in the previous 12 months (current asthma). <b>Results</b>: Of the subjects with asthma or wheezy breathing by the age of 7, as reported by their parents 25.6% (190/741) reported current asthma as an adult compared with 10.8% (81/753) of subjects without parent reported childhood asthma (P&lt;0.001). Factors measured at the age of 7 that independently predicted current asthma as an adult were being female (odds ratio 1.57; 95% confidence interval 1.19 to 2.08); having a history of eczema (1.45; 1.04 to 2.03); having a low mild forced expiratory flow rate (interquartile odds ratio 1.40; 1.15 to 1.71); having a mother or father with a history of asthma (1.74 (1.23 to 2.47) and 1.68 (1.18 to 2.38) respectively); and having childhood asthma (1.59; 1.10 to 2.29) and, if so, having the first attack after the age of 2 (1.66; 1.17 to 2.36) or having had more than 10 attacks (1.70; 1.17 to 2.48). Conclusion—Children with asthma reported by their parents in 1968 were more likely than not to be free of symptoms as adults. The subjects who had more severe asthma (especially if it developed after the age of 2 and was associated with reduced expiratory flow), were female, or had parents who had asthma were at an increased risk of having asthma as an adult. These findings have implications for the treatment and prognosis of childhood asthma, targeting preventive and educational strategies, and understanding the onset of asthma in adult life.
Cell surface adherence and endocytosis of protein transduction domains
Authors: Mathias Lundberg, Sara Wikström, Magnus Johansson
Journal: Molecular Therapy (2003)

Protein transduction domains (PTD), such as the HIV TAT and the herpes simplex virus VP22 proteins, are reported to translocate across the membranes of mammalian cells. The mechanism of PTD membrane translocation has largely remained elusive, but recent studies suggest that the reported PTD translocation is due to a fixation artifact. We have constructed and expressed the PTDs VP22, TAT, polyarginine, and polylysine fused to the green fluorescent protein to visualize these proteins in both living and fixed cells. The investigated PTDs strongly adhered to the surface of living cells and were internalized by constitutive endocytosis. No cytosolic or nuclear import of the proteins was detected. In contrast, the PTD-GFP fusion proteins were redistributed to the cytosol and nucleus directly after fixation. Our findings suggest that the PTDs only mediate cell surface adherence, a property shared with many other positively charged macromolecules. The cell surface adherence results in endocytosis and accumulation of proteins in endosomes. We suggest that the biological effects observed for PTD fusion proteins are due to cell surface interactions and internalization of the proteins into cells by classical endocytosis.
Associations of HLA-DRB and -DQB genes with two and five year outcome in rheumatoid arthritis.
Authors: K Eberhardt, E Fex, U Johnson, F A Wollheim
Journal: Annals of the Rheumatic Diseases (1996)

To evaluate the clinical usefulness of genomic HLA typing during the first five years of established rheumatoid arthritis (RA).The HLA-DRB and -DQB alleles were determined by restriction length polymorphisms and polymerase chain reaction amplification with sequence specific primers in 99 Swedish patients with RA. Clinical features after two and five years disease duration were related to the genetic pattern. Seventy four patients were seropositive, 25 had nodules, 90 developed erosions, and 15 required joint replacements. Twelve patients were in remission after five years. Disability was assessed by health assessment questionnaire, and radiographic damage in hands and feet by the Larsen method.Eighty seven per cent of the patients carried the conserved third hypervariable region sequence (HVR3), 32% had DRB1*04 on one allele, and 26% had DRB1*04 on both alleles (all frequencies significantly greater than in controls). Frequencies of DRB1*04 associated DQB*0301 and *0302 were normal. Patients carrying DRB1*04 on both alleles tended to have more radiographic changes after two years, but this difference had diminished after five years. Disability did not vary with regard to the genotype. Homozygous HVR3 patients had about three times greater risk of undergoing joint replacement. Homozygosity for HVR3 and presence of DQB*0302 both tended to be associated with erosive disease.We confirmed a strong association of disease with the presence of the shared epitope on one or two alleles. However, genotype was not strongly associated with disease severity after two and five years disease duration, and thus the value of genomic typing to select patients for early aggressive therapy is questionable.
Report of the American Diabetes Association's Task Force on Nutrition: Introduction
Authors: Aaron Vinik
Journal: Diabetes Care (1988)

Writing in the sixteenth century B.C., the Egyptians described diabetes as the dissolving of flesh in urine and promoted its treatment with diets high in carbohydrate as a means of combating the loss of fuels. Early in the first century, Aretaeus of Cappadocca endorsed these suggestions, recommending a diet of milk, cereals, and starch. By the early twentieth century, the whimsical rice, potato, and oatmeal diets had evolved from these beginnings and reached the apex of their popularity. The noted physician Willis—possibly more famous for the description of a circle of blood vessels at the base of the brain—endorsed such diets on the basis of the appearance of sweetness of the urine. Thus, many a medical student was obliged to taste urine before the advent of more advanced technology. Now a more sophisticated method is employed in which a treated strip of paper inserted in the urine is transposed, to a degree proportional to the quantity of glucose present, into one of the colors of the rainbow—a facility not generally endowed to the human taste bud.
Convulsive Disorders in Children, With Reference to Treatment With Ketogenic Diet
Authors: Jerome K. Merlis
Journal: JAMA (1964)

Despite the subtitle, the greater portion of this volume is devoted to a conventional discussion of the convulsive disorders of children. Dr. Keith has had a long experience with such disorders, but, unfortunately, he presents little in the way of statistical data derived from analysis of his own series. The section on the ketogenic diet is more informative. Dr. Keith is one of the few proponents of this admittedly difficult form of therapy, and he cites data indicating complete control of seizures in about one third of the cases. According to present day values, this is hardly a very striking figure. The ketogenic diet was introduced in 1922, at a time when the therapeutic armamentarium for convulsive disorders was very limited. The introduction of diphenylhydantoin ( Dilantin ) sodium in 1938 was a striking breakthrough, and since that time a number of new and highly effective drugs have come into common use.
Abstract 1904: Reversal of thymic involution and immunosuppression in tumor-bearing mice by IFN-γ
Authors: Roberto Carrio-Jardines, Vijaya Iragavarapu-Charyulu, Stephania Libreros, Ramon A. Garcia-Areas, Diana M. Lopez
Journal: Cancer Research (2010)

Abstract The thymus is a central lymphoid organ critical for the development and maintenance of an effective peripheral T cell repertoire. Most important, it provides a specialized environment for the selection of rearranged clones that will function appropriately in the adaptive immune response. The tumor-induced immunosuppression observed during murine mammary tumorigenesis has been associated with a profound thymus involution accompanied with a severe depletion of the most abundant subset of thymocytes; CD4+CD8+ double positive (DP) immature cells. Thymic involution has been observed in several model systems; including graft-vs-host disease, aging, and tumor development, however, the mechanisms involved in this phenomenon remain to be elucidated. Previous results from our laboratory have reported that the severe thymic atrophy and impaired T cell development seen in mammary tumor bearers are associated with an arrest in at least two steps of T cell differentiation, changes in the levels of crucial cytokines expressed in the thymus microenvironment, and a progressive increase in apoptosis during the tumor development mainly due to downregulation of important molecules that control programmed cell death. Moreover, we have shown that mice bearing the murine parental D1-DMBA-3 mammary tumor and tumors derived from the parental tumor, the DA-3, develop many changes in their cytokine production. For example, in mice bearing these tumors there is a decrease in the IFN-γ in the peripheral circulation and production of this crucial cytokine is greatly diminished in the T cells. In the present study we have used our DA-3 mammary tumor model to investigate whether the levels of IFN-γ have an important role in anti-tumor activity, in the pathogenesis of thymic atrophy as well as the tumor-induced immunosuppression in these mice. Interestingly, our results show that the overexpression of IFN-γ in DA-3 tumor cells results in a marked delay of tumor growth and a blockage in the tumor-associated thymus atrophy. Importantly, peripheral T cells from IFN-γ-transfected DA-3 tumor-bearing mice, show markedly high levels of this cytokine. Moreover, when thymuses from tumor-bearing mice that received IFN-γ were analyzed, thymic populations were very similar to those observed in the thymuses of normal mice. Collectively, our data suggest that the replacement of the faulty levels of IFN-γ in tumor bearers results in a delayed tumor growth and thymic involution leading to a decrease of tumor-induced immune suppression caused by the mammary tumor development. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1904.
Myocardial ischemia due to infrarenal aortic cross-clamping during aortic surgery in patients with severe coronary artery disease.
Authors: R R Attia, J D Murphy, M Snider, D G Lappas, R C Darling, E Lowenstein
Journal: Circulation (1976)

Hemodynamic measurements were performed and ECG recorded before and shortly after infrarenal aortic cross-clamping during operation for abdominal aortic aneurysm in five patients without evidence of heart disease (group I) and in ten patients with severe coronary artery disease (group II). All patients sustained an increase in systemic arterial pressure. Group I demonstrated a decrease in pulmonary artery, pulmonary capillary wedge (PCW), and central venous pressures when the aorta was clamped, whereas group II demonstrated an increase. The difference in response of the groups is significant (P less than 0.05). All three patients who responded to cross-clamping with increases of 7 mm Hg or greater in PCW demonstrated myocardial ischemia during cross-clamping. None of the values measured prior to cross-clamping predicted with certainty the response to cross-clamping. Sodium nitroprusside reversed the elevation of left ventricular filling pressure in all three patients, and in two patients, relieved evidence of myocardial ischemia concurrently. In the third patient, ventricular irritability was abolished by lidocaine and did not recur. We conclude that infrarenal aortic cross-clamping may cause myocardial ischemia in patients with severe coronary artery disease. This ischemia may be predicted by a rise in PCW at the time of cross-clamping, and vasodilator therapy is indicated in such patients.
Small Heat Shock Proteins and Protection Against Ischemic Injury in Cardiac Myocytes
Authors: Jody L. Martin, Ruben Mestril, Randa Hilal-Dandan, Laurence L. Brunton, Wolfgang H. Dillmann
Journal: Circulation (1997)

Overexpression of the inducible hsp70 protects against ischemic cardiac damage. However, it is unclear whether the small heat shock proteins hsp27 and alphaB-crystallin protect against ischemic injury.Our aim was to examine whether the overexpression of hsp27 and alphaB-crystallin in neonatal and adult rat cardiomyocytes would protect against ischemic injury. Recombinant adenovirus expressing hsp27 or alphaB-crystallin under the control of the cytomegalovirus promoter was used to infect cardiac myocytes at high efficiency as assessed by immunostaining. Overexpression was confirmed by Western blot analysis. Cardiomyocytes were subjected to simulated ischemic stress, and survival was estimated through assessment of lactate dehydrogenase and creatine phosphokinase release. The hsp27 overexpression decreased lactate dehydrogenase release by 45+/-7.5% in adult cardiomyocytes but had no effect in the neonatal cells. In contrast, alphaB-crystallin overexpression was associated with a decrease in cytosolic enzyme release in both adult (29+/-6.6%) and neonatal (32+/-5.4%) cardiomyocytes. Decreased endogenous hsp25 with an antisense adenovirus produced a 29+/-9.9% increase in damage with simulated ischemia. Overexpression of the inducible hsp70 in adult cardiomyocytes was associated with a 34+/-4.6% decrease in lactate dehydrogenase release and is in line with our previous results in neonatal cardiomyocytes.The increased expression of hsp27 and alphaB-crystallin through an adenovirus vector system protects against ischemic injury in adult cardiomyocytes. Likewise, the overexpression of alphaB-crystallin protects against ischemic damage in neonatal cardiomyocytes. Decreasing the high levels of endogenous hsp25 present in neonatal cardiomyocytes renders them more susceptible to damage caused by simulated ischemia.
Medical Student as Poet
Authors: M. THERESE SOUTHGATE
Journal: JAMA (1984)

For those who would see the science and technology of medicine textured with a little more of the humanistic mind, there are encouraging signs from Northeastern Ohio Universities College of Medicine in Rootstown, Ohio. For four months in 1982 the Human Values in Medicine Program at the college sponsored a poetry-writing competition open to medical students from all over the United States. Two hundred twenty-four students from 85 medical schools entered some 550 poems. The winner was Julie Deane Fishbein, a student at the University of Maryland School of Medicine, Baltimore, with "The Biologist," dedicated to her father. Second place went to Philip Clinton Bowman, Medical College of Virginia School of Medicine, Richmond, for "The Cooper River Bridge," and third to Diane M. Roston, The University of Wisconsin Medical School, Madison, for "On Studying Anatomy." Now comes a little book entitled Poetry:<i>A Collection of Poems Written by Medical Students</i>
Presidential Address on Ophthalmology &amp; General Medicine
Authors: H. Jackson
Journal: BMJ (1889)

No professional honour could be more pleasant to me than is the Presidency of the Ophthalmological Society.I thank you for it with all the greater heartiness because I am already very much in your debt for your selection of me to deliver the Bowman Lecture of1885,1 and to open a discussion on that most important neuro- logico-ophthalmological subject optic neuritis.2There is no de- partment of medicine which has greater attractions for me than ophthalmology has.It was the first subject I specially worked at after my student life, and I still think what I said when giving the annual address, 1877,3 before the Medical Society, that it was " the luckiest thing in my medical life that I began the scientific study of my profession at an ophthalmic hospital."Many years ago I had the good fortune to be Mr. Hutchinson's clinical assist- ant at Moorfields.I suppose it is to his example and teaching that I owe the beginning of the little scientific development I may have.At an ophthalmic hospital one has the opportunity of being
Kinetics and intracellular compartmentalization of HTLV-1 gene expression: nuclear retention of HBZ mRNAs
Authors: Francesca Rende, Ilaria Cavallari, Alberto Corradin, Micol Silic-Benussi, Frederic Toulza, Gianna M. Toffolo, Yuetsu Tanaka, Steven Jacobson, Graham P. Taylor, Donna M. D'Agostino, Charles R. M. Bangham, Vincenzo Ciminale
Journal: Blood (2011)
Comparison of Conventional-Dose vs High-Dose Conformal Radiation Therapy in Clinically Localized Adenocarcinoma of the Prostate
Authors: Anthony L. Zietman, Michelle L. DeSilvio, Jerry D. Slater, Carl J. Rossi, Daniel W. Miller, Judith A. Adams, William U. Shipley
Journal: JAMA (2005)

Clinically localized prostate cancer is very prevalent among US men, but recurrence after treatment with conventional radiation therapy is common.To evaluate the hypothesis that increasing the radiation dose delivered to men with clinically localized prostate cancer improves disease outcome.Randomized controlled trial of 393 patients with stage T1b through T2b prostate cancer and prostate-specific antigen (PSA) levels less than 15 ng/mL randomized between January 1996 and December 1999 and treated at 2 US academic institutions. Median age was 67 years and median PSA level was 6.3 ng/mL. Median follow-up was 5.5 (range, 1.2-8.2) years.Patients were randomized to receive external beam radiation to a total dose of either 70.2 Gy (conventional dose) or 79.2 Gy (high dose). This was delivered using a combination of conformal photon and proton beams.Increasing PSA level (ie, biochemical failure) 5 years after treatment.The proportions of men free from biochemical failure at 5 years were 78.8% [corrected] (95% confidence interval, 73.1%-84.6%) [corrected] for conventional-dose and 91.3% [corrected] (95% confidence interval, 87.2%-95.4%) [corrected] for high-dose therapy (P<.001), a 59% [corrected] reduction in the risk of failure. The advantage to high-dose therapy was statistically significant [corrected] in both the low-risk subgroup [corrected] (risk reduction, 84% [P<.001]) [corrected] There has been no significant difference in overall survival rates between the treatment groups. Only 1% of patients receiving conventional-dose and 2% receiving high-dose radiation experienced acute urinary or rectal morbidity of Radiation Therapy Oncology Group (RTOG) grade 3 or greater. So far, only 2% and 1%, respectively, have experienced late morbidity of RTOG grade 3 or greater.Men with clinically localized prostate cancer have a lower risk of biochemical failure if they receive high-dose rather than conventional-dose conformal radiation. This advantage was achieved without any associated increase in RTOG grade 3 acute or late urinary or rectal morbidity.
CLINICAL ASSESSMENT OF NO-REFLOW IN HUMANS: COMPARISON BETWEEN CARDIAC MAGNETIC RESONANCE AND ANGIOGRAPHY
Authors: Martina Perazzolo Marra, Luisa Cacciavillani, Francesco Corbetti, Giuseppe Tarantini, Cristina Basso, Armando Marzari, Manuel De Lazzari, Veronica Spadotto, Filippo Zilio, Sabino Iliceto
Journal: Journal of the American College of Cardiology (2010)
Treatment of Acute Hepatitis C with Interferon Alfa-2b
Authors: Elmar Jaeckel, Markus Cornberg, Heiner Wedemeyer, Teresa Santantonio, Julika Mayer, Myrga Zankel, Giuseppe Pastore, Manfred Dietrich, Christian Trautwein, Michael P. Manns
Journal: New England Journal of Medicine (2001)

In people who are infected with the hepatitis C virus (HCV), chronic infection often develops and is difficult to eradicate. We sought to determine whether treatment during the acute phase could prevent the development of chronic infection.
A place of safety
Authors: Andrew Ludman, Sian Ludman
Journal: BMJ (2006)

Throughout our medical training, my wife and I have often bemoaned the confused elderly person who appears in the casualty department for no apparent medical reason in the middle of the night. A recent event has helped change our opinion. 

We were returning from a wedding late at night and came across a confused elderly woman wandering outside our house. She was wearing only a …
Low-Density Lipoprotein Subclass Patterns and Risk of Myocardial Infarction
Authors: Melissa A. Austin
Journal: JAMA (1988)

The association of low-density lipoprotein (LDL) subclass patterns with coronary heart disease was investigated in a case-control study of nonfatal myocardial infarction. Subclasses of LDL were analyzed by gradient gel electrophoresis of plasma samples from 109 cases and 121 controls. The LDL subclass pattern characterized by a preponderance of small, dense LDL particles was significantly associated with a threefold increased risk of myocardial infarction, independent of age, sex, and relative weight. Plasma levels of high-density lipoprotein cholesterol were decreased, and levels of triglyceride, very low-density lipoproteins, and intermediate-density lipoproteins were increased in subjects with this LDL subclass pattern. Multivariate logistic regression analyses showed that both high-density lipoprotein cholesterol and triglyceride levels contributed to the risk associated with the small, dense LDL subclass pattern. Thus, the metabolic trait responsible for this LDL subclass pattern results in a set of interrelated lipoprotein changes that lead to increased risk of coronary heart disease.