tbuckley/cabot-search huggingface dataset:
Multiple Reduced-intensity Conditioning Regimens Facilitate Correction of Fabry Mice After Transplantation of Transduced Cells
Authors: Sheng-Ben Liang, Makoto Yoshimitsu, Armando Poeppl, Vanessa I Rasaiah, Jianhui Cai, Daniel H Fowler, Jeffrey A Medin
Journal: Molecular Therapy (2007)

Hematopoietic cell transplantation can impact lysosomal storage disorders (LSDs) and will be enhanced by gene therapy. Transduced cells in LSDs often secrete the therapeutic hydrolase, which can be used by bystander cells. However, toxicity associated with myeloablative transplant preparative regimens limits many applications of this approach in gene therapy. We hypothesized that reduced-intensity (RI) conditioning regimens would allow stable engraftment of therapeutically transduced cells and allow correction of Fabry disease. We transplanted transduced cells into Fabry mice receiving eight different clinically relevant chemotherapy- and/or radiotherapy-based RI conditioning regimens generating modest and transient lymphoid/myeloid cell depletion. Two comprehensive transplantation Protocols were performed. Firstly, transplantation of 0.38 x 10(6) gene-modified stem/progenitor cells was nominally effective; none of the RI regimens led to stable alpha-galactosidase A (alpha-gal A) correction. Secondly, transduced cells were preselected for functional transgene expression and transplanted at a higher dose (0.72 x 10(6) cells). Each RI regimen yielded engraftment of functional transgene-positive cells through 180 days along with increased plasma alpha-gal A activity. Importantly, the RI regimens mediated broad organ enzyme correction and were not associated with immune responses against alpha-gal A. RI conditioning thus has an important role in gene therapy for LSDs; a variety of regimens can be effective in this context.
When flesh thinks
Authors: Colin Martin
Journal: BMJ (2006)

A rtist Susan Aldworth's interest in the mystery of human consciousness, which she has explored in her work over the past five years, was triggered by a radiological investigation carried out on Christmas Day 1999, following her suspected brain haemorrhage. “You are lying on a bed looking up at your brain scan live on a bank of monitors. You are seeing the inside of your brain with your brain. You are thinking about what …
Skeletal muscle strength and endurance in patients with mild COPD and the effects of weight training
Authors: C.J. Clark, L.M. Cochrane, E. Mackay, B. Paton
Journal: European Respiratory Journal (2000)

This study poses two questions: 1) is there an abnormality in isokinetic skeletal muscle strength and endurance in mild chronic obstructive pulmonary disease (COPD)? and 2) what is the effect of a randomized, controlled, 12 week hospital outpatient weight training programme in terms of skeletal muscle function and exercise tolerance? Upper and lower limb isokinetic maximum and sustained muscle function were compared in 43 COPD patients (age 49+/-11 yrs), mean forced expiratory volume in one second (FEV1) 77+/-23% pred and 52 healthy, sedentary subjects (age 51 (10) yrs), mean FEV1 109+/-16% pred. The 43 COPD patients were randomly allocated into training (n=26) and control (n=17) groups. Isokinetic and isotonic muscle function, whole body endurance, maximal exercise capacity and lung function were measured. The COPD patients had reduced isokinetic muscle function (with the exception of sustained upper limb strength) as compared with healthy sedentary subjects. Muscle function improved after weight training in the COPD patients. Whole body endurance during treadmill walking also improved with no change in maximal oxygen consumption. A deficit in skeletal muscle function can be identified in patients with mild chronic obstructive pulmonary disease which cannot be explained by factors such as hypoxaemia and malnutrition. Intervention with weight training is effective in countering this deficit which the authors conclude is probably due to muscle deconditioning.
Influence of ITPA polymorphisms on decreases of hemoglobin during treatment with pegylated interferon, ribavirin, and telaprevir
Authors: Fumitaka Suzuki, Yoshiyuki Suzuki, Norio Akuta, Hitomi Sezaki, Miharu Hirakawa, Yusuke Kawamura, Tetsuya Hosaka, Masahiro Kobayashi, Satoshi Saito, Yasuji Arase, Kenji Ikeda, Mariko Kobayashi, Kazuaki Chayama, Naoyuki Kamatani, Yusuke Nakamura, Yuzo Miyakawa, Hiromitsu Kumada
Journal: Hepatology (2010)

Polymorphisms of the inosine triphosphatase (ITPA) gene influence anemia during pegylated interferon (PEG-IFN) and ribavirin (RBV) therapy, but their effects during triple therapy with PEG-IFN, RBV, and telaprevir are not known. Triple therapy for 12 weeks, followed by PEG-IFN and RBV for 12 weeks, was given to 49 patients with RBV-sensitive (CC at rs1127354) and 12 with RBV-resistant (CA/AA) ITPA genotypes who had been infected with hepatitis C virus (HCV) of genotype 1. Decreases in hemoglobin levels were greater in patients with CC than CA/AA genotypes at week 2 (-1.63 ± 0.92 vs. -0.48 ± 0.75 g/dL, P = 0.001) and week 4 (-3.5 ± 1.1 vs. -2.2 ± 0.96, P = 0.001), as well as at the end of treatment (-2.9 ± 1.1 vs. -2.0 ± 0.86, P = 0.013). Risk factors for hemoglobin <11.0 g/dL at week 4 were female gender, age >50 years, body mass index (BMI) <23, and CC at rs1127354 by multivariate analysis. RBV dose during the first 12 weeks was smaller in patients with CC than CA/AA genotypes (52 ± 14% vs. 65 ± 21% of the target dose, P = 0.039), but the total RBV dose was no different between them (49 ± 17% and 54 ± 18% of the target, P = 0.531). Sustained virological response (SVR) was achieved in 70% and 64% of them, respectively (P = 0.724).ITPA polymorphism influences hemoglobin levels during triple therapy, particularly during the first 12 weeks while telaprevir is given. With careful monitoring of anemia and prompt adjustment of RBV dose, SVR can be achieved comparably frequently between patients with CC and CA/AA genotypes.
The professional scientist; a study of American chemists
Authors: Battle S. Searcy
Journal: JAMA (1963)

Many disciplines, as they emerge from the modern university into the industrial world, demand the right to be called professional. Foremost among these is chemistry, which is no longer content to perpetuate itself in the academic halls. Industrial requirements for the chemical specialist have prompted this change of status. The professional self-image of chemists in their altered roles is the subject of an extensive sociological study. Using sampling techniques among chemists, the authors find that only medicine, law, and dentistry—the traditional professions —hold higher prestige than chemistry. Nevertheless, chemists, from research administrators and academicians to bench chemists and chemical engineers, all consider themselves professional persons. Important considerations in this study include the structural ladder of the chemist's world, recruitment and careers in this field, and the role of the professional organization in helping its members. As this is the first large-scale analysis dealing with new professions in the contemporary world,
A SPLINTER OF WOOD LODGED IN THE URINARY BLADDER
Authors: Jay J. Crane
Journal: JAMA (1935)

R. B., a boy, aged 7½ years, while playing, July 1, 1934, fell from a garage roof, lighting astride a picket fence. Examination revealed a laceration 1 cm. long on the inner aspect of the upper third of the left thigh, through which a probe was passed, but no foreign body was found. During the first four days the only symptom complained of was a dull ache over the bladder area, which gradually disappeared. A few red blood cells were found in the urine immediately after the accident and continued to be present during this period. By the end of the second week pus was found in the urine, accompanied by a tickling sensation in the urethra during the act of micturition. The laceration now was entirely healed, and it was thought safe to allow the patient to go to a boys' camp, where he could be under observation. Here
CCL8 is a potential molecular candidate for the diagnosis of graft-versus-host disease
Authors: Tsukasa Hori, Yasuyoshi Naishiro, Hitoshi Sohma, Nobuhiro Suzuki, Naoki Hatakeyama, Masaki Yamamoto, Tomoko Sonoda, Yuka Mizue, Kohzoh Imai, Hiroyuki Tsutsumi, Yasuo Kokai
Journal: Blood (2008)
Peers consider plan to amend UK law over assisted suicide abroad
Authors: C. Dyer
Journal: BMJ (2009)

Parliamentarians will make a new attempt next month to amend the law to give protection from prosecution to friends and family members who help a terminally ill person travel outside the United Kingdom for assisted suicide.

The former health secretary Patricia Hewitt put down an amendment to the Coroners and Justice Bill when it was going through the House of Commons in March but, because of government timetabling, the time for debate ran out and the amendment was never reached.

Now peers plan to table a similar amendment to the bill for …
Smoothened is a master regulator of adult liver repair
Authors: Gregory A. Michelotti, Guanhua Xie, Marzena Swiderska, Steve S. Choi, Gamze Karaca, Leandi Krüger, Richard Premont, Liu Yang, Wing-Kin Syn, Daniel Metzger, Anna Mae Diehl
Journal: Journal of Clinical Investigation (2013)

When regenerative processes cannot keep pace with cell death, functional epithelia are replaced by scar. Scarring is characterized by both excessive accumulation of fibrous matrix and persistent outgrowth of cell types that accumulate transiently during successful wound healing, including myofibroblasts (MFs) and progenitors. This suggests that signaling that normally directs these cells to repair injured epithelia is deregulated. To evaluate this possibility, we examined liver repair during different types of liver injury after Smoothened (SMO), an obligate intermediate in the Hedgehog (Hh) signaling pathway, was conditionally deleted in cells expressing the MF-associated gene, αSMA. Surprisingly, blocking canonical Hh signaling in MFs not only inhibited liver fibrosis but also prevented accumulation of liver progenitors. Hh-sensitive, hepatic stellate cells (HSCs) were identified as the source of both MFs and progenitors by lineage-tracing studies in 3 other strains of mice, coupled with analysis of highly pure HSC preparations using flow cytometry, immunofluorescence confocal microscopy, RT-PCR, and in situ hybridization. The results identify SMO as a master regulator of hepatic epithelial regeneration based on its ability to promote mesenchymal-to-epithelial transitions in a subpopulation of HSC-derived MFs with features of multipotent progenitors.
Preoperative triglycerides predict post-coronary artery bypass graft survival in diabetic patients: a sex analysis.
Authors: D L Sprecher, G L Pearce, E M Park, F J Pashkow, B J Hoogwerf
Journal: Diabetes Care (2000)

Hypertriglyceridemia is commonly observed in association with diabetes. Despite cross-sectional studies and isolated longitudinal analyses in patients without coronary artery disease, the suggestion that triglyceride levels are relevant to subsequent cardiovascular events in the setting of diabetes remains controversial. This study evaluates the predictive value of serum triglyceride levels on mortality in post-coronary artery bypass graft (CABG) diabetic patients with subsequent analysis by sex.This longitudinal observational study involving a large metropolitan hospital consists of 1,172 diabetic post-CABG patients (792 men and 380 women) with lipid data collected between the years 1982 and 1992. Cox proportional hazards regression models were used to estimate the risk of mortality and cardiac events associated with triglyceride levels in the highest quartile (> 2.90 mmol/l for men and > 3.12 mmol/l for women).Elevated preoperative serum triglyceride values in post-CABG subjects with diabetes were correlated with increased overall mortality (hazard ratio [HR] 1.26, 95% CI 1.00-1.59). The greatest influence of triglyceride levels was observed on overall (1.89, 1.30-2.73) and event-free survival (1.49, 1.06-2.08) in women. High triglyceride values were also modestly related to risk of cardiac events in diabetic men (1.28, 0.99-1.66).These data suggest that increased preoperative triglyceride levels predict increased late mortality and cardiac event risk in diabetic post-CABG patients, more strongly in women than in men.
Compulsory Premarital Screening for HIV
Authors: Cory Franklin
Journal: JAMA (1988)

<h3>To the Editor.</h3> —I am questioning some of the methods and conclusions in the article by Cleary et al.<sup>1</sup> Although there are no studies, to my knowledge, documenting the prevalence of human immunodeficiency virus infection among those planning marriage, the prevalence estimates that the authors use in their calculations, while not necessarily wrong, are clearly low. Their prevalence data assume a rate of infection of 70 per 100 000 among men aged 18 to 44 years and seven per 100 000 among others. This assumption would yield fewer than 200 000 infected individuals in the country's overall population, which is in contrast to a study quoted by the authors that estimated a yield of 1 to 2 million infected individuals.<sup>2</sup>The "worst-case" situation that the authors construct uses a prevalence rate only twice as high as the original assumption. A more reasonable worst-case scenario would use a prevalence
Hepatic Accumulation and Intracellular Binding of Conjugated Bilirubin
Authors: Allan W. Wolkoff, Jeanne N. Ketley, Jeanne G. Waggoner, Paul D. Berk, William B. Jakoby
Journal: Journal of Clinical Investigation (1978)

After the intravenous injection of unconjugated [(3)H]bilirubin into normal Sprague-Dawley and Wistar R rats, radiolabeled bile pigments rapidly accumulated in the liver. By 1.5 min after injection, an average of 36% of the injected isotope was present in liver homogenates. Between 3 and 15 min, 37-64% of the total intrahepatic radiolabeled bilirubin was conjugated, as demonstrated by extraction of label into the polar phase of a solvent partition system. This indicates both rapid conjugation, and accumulation of conjugated bilirubin within the liver cell. Fluorometric determination of the dissociation constants of purified bilirubin and its mono- and diglucuronides for homogeneous preparations of two human and four rat glutathione S-transferases, including ligandin, revealed avid binding of all three bile pigments to this class of proteins. Hence, the observation that the intrahepatic bile pigment pool contains substantial amounts of conjugated bilirubin can be attributed to the high binding affinities observed. Thin-layer chromatographic analysis of the (3)H-pigments produced by p-iodoaniline diazotization of homogenates and cytosol demonstrated that the intrahepatic pool of conjugated bilirubin was almost exclusively monoglucuronide. Examination of radiolabeled bilirubin conjugates excreted in bile during the first 20 min after injection of [(3)H]bilirubin showed no preferential excretion of diglucuronide. These studies indicate that (a) both bilirubin and its monoglucuronide accumulate within the liver cell as ligands with the glutathione S-transferase; and (b) bilirubin diglucuronide does not significantly accumulate within the general intrahepatocellular pool of protein-bound bile pigments. The latter observation is compatible with the formation and excretion of bilirubin diglucuronide directly from the canalicular pool of the liver cell.
Muscarinic receptor subtypes in cilia-driven transport and airway epithelial development
Authors: M. K. Klein, R. V. Haberberger, P. Hartmann, P. Faulhammer, K. S. Lips, B. Krain, J. Wess, W. Kummer, P. König
Journal: European Respiratory Journal (2009)

Ciliary beating of airway epithelial cells drives the removal of mucus and particles from the airways. Mucociliary transport and possibly airway epithelial development are governed by muscarinic acetylcholine receptors but the precise roles of the subtypes involved are unknown. This issue was addressed by determining cilia-driven particle transport, ciliary beat frequency, and the composition and ultrastructural morphology of the tracheal epithelium in M1–M5 muscarinic receptor gene-deficient mice. Knockout of M3 muscarinic receptors prevented an increase in particle transport speed and ciliary beat frequency in response to muscarine. Furthermore, the ATP response after application of muscarine was blunted. Pretreatment with atropine before application of muscarine restored the response to ATP. Additional knockout of the M2 receptor in these mice partially restored the muscarine effect, most likely through the M1 receptor, and normalised the ATP response. M1, M4 and M5 receptor-deficient mice exhibited normal responses to muscarine. None of the investigated mutant mouse strains had any impairment of epithelial cellular structure or composition. In conclusion, M3 receptors stimulate whereas M2 receptors inhibit cilia-driven particle transport. The M1 receptor increases cilia-driven particle transport if the M3 and M2 receptors are missing. None of the receptors is necessary for epithelial development.
Experimental Medical Ecology
Authors: Howard A. Schneider
Journal: JAMA (1965)

Ecology is defined as that branch of biology concerned with the mutual relations between organisms and their environment. Medical ecology, then, concerns itself with man, with his mutual relations within his species, with all other species, and finally, with all of these phenomena as they are related to the environment. The word "medical" conveys further a value judgment, that all of what has just been said is to be viewed as opening a path to measures implementing the preservation and restoration of health. It is a large undertaking, indeed, and with all of its myriad aspects it is a staggering one. Considering that the classical mechanics of physics, even today, has not solved the problem posed by the mutual relations involving the position and momentum of only three single bodies, there is good reason to be humble about medical ecology. But, if we should be humble, there is no need
Community falls prevention for people who call an emergency ambulance after a fall: randomised controlled trial
Authors: P. A. Logan, C. A. C. Coupland, J. R. F. Gladman, O. Sahota, V. Stoner-Hobbs, K. Robertson, V. Tomlinson, M. Ward, T. Sach, A. J. Avery
Journal: BMJ (2010)

<b>Objective</b> To evaluate whether a service to prevent falls in the community would help reduce the rate of falls in older people who call an emergency ambulance when they fall but are not taken to hospital. <b>Design</b> Randomised controlled trial. <b>Setting</b> Community covered by four primary care trusts, England. <b>Participants</b> 204 adults aged more than 60 living at home or in residential care who had fallen and called an emergency ambulance but were not taken to hospital. <b>Interventions</b> Referral to community fall prevention services or standard medical and social care. <b>Main outcome measures</b> The primary outcome was the rate of falls over 12 months, ascertained from monthly diaries. Secondary outcomes were scores on the Barthel index, Nottingham extended activities of daily living scale, and falls efficacy scale at baseline and by postal questionnaire at 12 months. Analysis was by intention to treat. <b>Results</b> 102 people were allocated to each group. 99 (97%) participants in the intervention group received the intervention. Falls diaries were analysed for 88.6 person years in the intervention group and 84.5 person years in the control group. The incidence rates of falls per year were 3.46 in the intervention group and 7.68 in the control group (incidence rate ratio 0.45, 95% confidence interval 0.35 to 0.58, P&lt;0.001). The intervention group achieved higher scores on the Barthel index and Nottingham extended activities of daily living and lower scores on the falls efficacy scale (all P&lt;0.05) at the 12 month follow-up. The number of times an emergency ambulance was called because of a fall was significantly different during follow-up (incidence rate ratio 0.60, 95% confidence interval 0.40 to 0.92, P=0.018). <b>Conclusion</b> A service to prevent falls in the community reduced the fall rate and improved clinical outcome in the high risk group of older people who call an emergency ambulance after a fall but are not taken to hospital. <b>Trial registration</b> Current Controlled Trials ISRCTN67535605.
Lymphokine-mediated bone resorption requires endogenous prostaglandin synthesis.
Authors: R S Bockman, M A Repo
Journal: The Journal of Experimental Medicine (1981)

Enhanced synthesis of prostaglandin (PG) E by explanted fetal rat bones was initiated by lymphocyte-conditioned media but not by physiological levels of parathyroid hormone. Rapid release of PGE from bone occurred only when the lymphokine was present. Synthesis of PGE preceded and was necessary for the bone resorption caused by the lymphokine preparation. Local production of prostaglandins in response to inflammatory cell or tumor-derived factors may in part be responsible for the localized bone loss that occurs in certain pathological states.
A Case of Pustular Granulomatosis, Anaemia and Hypo-beta Globulinaemia.
Authors: Peter J. C. Ashurst
Journal: British Journal of Dermatology (1964)

Journal Article A Case of Pustular Granulomatosis, Anaemia and Hypo‐beta Globulinaemia. Get access Peter J. C. Ashurst Peter J. C. Ashurst Manchester Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 76, Issue 2, 1 February 1964, Pages 96–97, https://doi.org/10.1111/j.1365-2133.1964.tb14485.x Published: 01 February 1964
Pyrogenic Reactions After Inadvertent Infusion of Endotoxin During Cardiac Catheterizations
Authors: M. P. Reyes, S. Ganguly, M. Fowler, W. J. Brown, B. G. Gatmaitan, C. Friedman, A. M. Lerner
Journal: Annals of Internal Medicine (1980)

In April 1976 the attack rate of chills and fever with or without falls in blood pressure increased in association with cardiac catheterizations. Fevers were associated with coronary angiography and right and left heart catheterizations. Blood cultures were negative, and reactions did not correlate with amounts of contrast materials infused or with procedures done by a single operator. Significant numbers of Acinetobacter calcoaceticus (var. anitratus) and a Pseudomonas species were cultured from hospital-reservoir distilled water when it was flushed through a catheter before gas sterilization. This same water after ethylene oxide sterilization contained 2 X 105 ng/mL of endotoxin by limulus lysate test and was positive by rabbit pyrogen test. When washed reusable cardiac catheters were sterilized daily or when disposable catheters were substituted, febrile reactions ended. Pyrogenic reactions in patients undergoing cardiac catheterizations corrrelated with emptying retained endotoxin with injected contrast material from reused washed-sterilized catheters.
TRENDS IN ACUTE ISCHEMIC CEREBROVASCULAR EVENTS ASSOCIATED WITH ATRIAL FIBRILLATION IN THE LAST DECADE IN THE UNITED STATES: TIME FOR AN APPRAISAL OF THE PROGRESS?
Authors: Arun Raghav Mahankali Sridhar, Madhu Reddy, Ryan Maybrook, Arun Kanmanthareddy, Jayasree Pillarisetti, Buddhadeb Dawn, Sudharani Bommana, Donita Atkins, Dhanunjaya Lakkireddy
Journal: Journal of the American College of Cardiology (2014)
Blockade of receptor activator of nuclear factor-κB (RANKL) signaling improves hepatic insulin resistance and prevents development of diabetes mellitus
Authors: Stefan Kiechl, Jürgen Wittmann, Andrea Giaccari, Michael Knoflach, Peter Willeit, Aline Bozec, Alexander R Moschen, Giovanna Muscogiuri, Gian Pio Sorice, Trayana Kireva, Monika Summerer, Stefan Wirtz, Julia Luther, Dirk Mielenz, Ulrike Billmeier, Georg Egger, Agnes Mayr, Friedrich Oberhollenzer, Florian Kronenberg, Michael Orthofer, Josef M Penninger, James B Meigs, Enzo Bonora, Herbert Tilg, Johann Willeit, Georg Schett
Journal: Nature Medicine (2013)