tbuckley/cabot-search huggingface dataset:
Carrier Cell–mediated Delivery of a Replication-competent Adenovirus for Cancer Gene Therapy
Authors: Katsuyuki Hamada, Junzo Desaki, Kou Nakagawa, Ting Zhang, Toshiro Shirakawa, Akinobu Gotoh, Masatoshi Tagawa
Journal: Molecular Therapy (2007)

Although replication-competent viruses have been developed to treat cancers, their cytotoxic effects are insufficient, as infection is inhibited by the generation of neutralizing antibodies. To address this limitation, we developed a carrier cell system to deliver a replication-competent adenovirus. Carrier cells infected with replication-competent adenovirus were incubated with target cancer cells in a high titer of anti-adenovirus antibody. Carrier cells were injected into syngeneic subcutaneous tumors after immunization with adenovirus. Carrier cell-derived cell fragments containing viral particles were engulfed by proliferative target cancer cells. This engulfment-mediated transfer of adenovirus was not inhibited by the anti-adenovirus antibody and enabled repetitive infection. After the induction of anti-adenoviral cytotoxic T-lymphocyte (CTL) responses by immunization with adenovirus, administration of carrier cells infected with a replication-competent adenovirus induced complete tumor regression. Adenovirus-GM-CSF augmented the anti-tumor effect of carrier cells by increasing anti-adenoviral and anti-tumoral CTL responses and decreased the number of injections of carrier cells required to induce complete tumor regression. This novel carrier cell-mediated viral transfection system might prove useful in a variety of cancer therapies.
REDUCTION IN VENTRICULAR WALL THICKNESS FOLLOWING HIGH-DOSE CHEMOTHERAPY AND STEM-CELL TRANSPLANTATION FOR AL CARDIAC AMYLOIDOSIS
Authors: Frederick L. Ruberg, Vaishali Sanchorawala, John Berk, Kathleen T. Finn, Martha Skinner, David C. Seldin, Hans Meier-Ewert
Journal: Journal of the American College of Cardiology (2010)
Jaeger's Atlas of Diseases of the Ocular Fundus, With New Descriptions, Revisions and Additions
Authors: Albert M. Potts
Journal: JAMA (1972)

This reprinting of the plates from Jaeger's 1869 atlas of the fundus oculi is a worthy contribution to the history of ophthalmology and a fine esthetic experience for the viewer. It was certainly a labor of love on the part of Dr. Albert, the editor who retrieved the original paintings from the archives of the College of Physicians of Philadelphia. The paintings reached that repository as a bequest from Dr. William F. Norris, the senior author of the Norris and Oliver ophthalmology text so familiar to a previous generation of American medical students. Dr. Norris, the first Clinical Professor of Ophthalmology at the University of Pennsylvania, purchased the paintings from the estate of Jaeger after the death of the latter in 1884. The faithfulness of reproduction by Jaeger of normal and pathological detail is truly remarkable. Quite curious is his reproduction of the excavated glaucomatous disk as an elevation. Anyone
Topoisomerase Inhibition Accelerates Gene Expression after Adeno-associated Virus-mediated Gene Transfer to the Mammalian Heart
Authors: Konkal-Matt R Prasad, Yaqin Xu, Zequan Yang, Marie-Claire Toufektsian, Stuart S Berr, Brent A French
Journal: Molecular Therapy (2007)

Utility of adeno-associated virus 2 (AAV2) vectors for cardiac gene therapy is limited by the prolonged lag phase before maximal gene expression. Topoisomerase inhibition can induce AAV2-mediated gene expression in vivo, but with variable success in different tissues. In this study, we demonstrate that topoisomerase inhibition can accelerate AAV2-mediated gene expression in the mouse heart. We used an AAV2 vector expressing firefly luciferase and monitored expression kinetics using non-invasive bioluminescence imaging. In the group receiving vector alone, cardiac luciferase activity was evident from week 2 onward and increased progressively to reach a steady plateau by 9 weeks postinjection. In the group receiving vector and camptothecine (CPT), luciferase expression was evident from days 2 to 4 onward and increased rapidly to reach a steady plateau by 3-4 weeks postinjection, nearly three times faster than in the absence of CPT (P<0.05). Southern blot analysis of AAV2 genomes in cardiac tissue showed rapid conversion of the AAV2 genome from its single-stranded to double-stranded form in CPT-treated mice. Non-invasive determinations of luciferase expression correlated well with in vitro luciferase assays. Direct injection of the AAV2 vector and long-term luciferase gene expression had no detectable effects on normal cardiac function as assessed by magnetic resonance imaging.
Fortnightly review: Environmental control systems for people with a disability: an update
Authors: D J Wellings, J Unsworth
Journal: BMJ (1997)

It is of great importance that disabled people should have sufficient help to achieve their potential.There are many ways of reducing handicap.Aids for mobility and communication are well known, but the use of "environmental control systems" is less well described. 1he collaboration of technologists, engineers, therapists, and medical staff has led to the development of systems that enable people with a wide range of impairments to control their home environment and offer some choice to the individual (R S F Schilling, unpublished). MethodThis review is based on a literature search in late 1995 and was financed by the NHS research and development programme for people with physical and complex disabilities.In view of the paucity of publications on the subject, we used a wide range of sources.We searched the following on-line and CD ROM databases: Medline, CINAHL, PsychLIT, BIDS, ASSIA PLUS, ERIC.We included early work on environmental control systems and case reports to give a historical perspective.We have highlighted the technological aspects of equipment design by including papers on microelectronics and robotics.We also included several official publications to provide an insight into the organisational aspects of provision of environmental control systems.Finally, much valuable information came from personal contact with colleagues interested in environmental control systems, disability organisations, and manufacturers.
Febrile Neutropenia and Infection in the ASCENT Studies
Authors: Michael Fink
Journal: Journal of Clinical Oncology (2011)

TO THE EDITOR: In the Androgen-Independent Prostate Cancer Study of Calcitriol Enhancing Taxotere–2 (ASCENT-2), Scher et al found no effect of DN-101, a high-concentration formulation of calcitriol, when given in combination with docetaxel for treatment of castration-resistant prostate cancer. This result contradicts the antitumoral effect found with DN-101 in the ASCENT-1 study, which had a different design that may have contributed to the contradictory results. Regarding the toxicity, ASCENT-2 reports a result not mentioned in the discussion, which, however, is supported by ASCENT-1: the rate of febrile neutropenia was 1.0% in the DN-101 arm and was 4.6% in the control arm. This difference, in my opinion, is statistically highly significant (P .001 with the 2 test). Surprisingly, pneumonias showed no difference, with 3.1% in the DN-101 and 2.9% in the control arm. However, in ASCENT-1, the rate of grades 3 to 4 infections under DN-101 was also lower, with eight occurrences with DN-101 and 13 occurrences in the control group. Similarly, in a recent pilot study with 81 patients who had suspected infection, patients with baseline 25-hydroxyvitamin D (25-OHD) levels less than 75 nmol/L (reference value, 50 to 150 nmol/L; optimal value, 75 nmol/L) were more likely to have severe sepsis than patients with 25-OHD levels 75 nmol/L (61% v 24%; P .006). All four patients who died during the index hospitalization had 25-OHD levels less than 75 nmol/L. In theory, these correlations are supported by the proven antibacterial and the highly probable antiviral effects of vitamin D. Recently, I reported on two patients with low initial 25-OHD levels and a marked improvement of chemotherapy-induced adverse effects during vitamin D treatment. A challenging aspect concerning adverse effects is undoubtedly the prophylaxis and treatment of leukopenic infections. Therefore, the difference in the rate of febrile neutropenias and infections with and without DN-101, which is not discussed by Scher et al, could be the most relevant result of the ASCENT studies.
A multicenter study of recombinant human interleukin 12 for the treatment of chronic hepatitis C virus infection in patients nonresponsive to previous therapy
Authors: Paul J. Pockros, Keyvr Patel, Christopher O'Brien, Myron Tong, Coleman Smith, Vinod Rustgi, Robert L. Carithers, John G. McHutchison, Elizabeth Olek, Michael F. DeBruin
Journal: Hepatology (2003)

Recombinant human interleukin 12 (IL–12) is an immunomodulatory cytokine that is active against several viruses. Treatment options in patients with chronic hepatitis C with nonresponse to interferon (IFN)–based therapy are limited. Prior dose–ranging studies have indicated drug tolerability and transient suppression of hepatitis C virus (HCV) RNA by IL–12. The aim of this study was to determine the safety and efficacy of prolonged IL–12 therapy in patients who have failed treatment with IFN–α ± ribavirin. A total of 225 patients at 21 U.S. sites who had a history of nonresponse to IFN–α or combination IFN–α plus ribavirin for treatment of HCV were randomized to 500 ng/kg IL–12 or placebo subcutaneously twice weekly for 12 weeks. The groups were then unblinded; patients receiving IL–12 continued for another 36 weeks, and the placebo group received 48 weeks of treatment with IL–12 in an open–label fashion. HCV RNA, serum alanine aminotransferase (ALT) level, and a repeat liver biopsy were assessed at 24 weeks following therapy. Approximately 1% (2 of 160) of nonresponsive patients enrolled for treatment had a sustained virologic response to IL–12 therapy, but 3% (7 of 225) developed severe adverse events probably related to treatment, resulting in early termination of the trial. Common adverse effects reported by most patients included chills, fever, fatigue, headache, and arthralgia. At termination of the study, 160 patients had received at least 8 weeks of treatment with IL–12. Paired liver biopsy specimens were available for evaluation in 54 patients, but there were no significant changes in Knodell fibrosis or histologic activity index (HAI) scores. In conclusion, IL–12 as monotherapy at the doses used in this trial for chronic hepatitis C has low efficacy, was poorly tolerated, and is unlikely to provide an alternative to conventional IFN–based therapy.
Principles and Practice of Ophthalmology
Authors: Benjamin H. Ticho
Journal: JAMA (1994)

In his preface, Dr Jakobiec states, "What we have aimed for is to provide the generalist with a digestible up-to-date overview of ophthalmology and also to provide the superspecialist with readily accessible introductions to topics outside his or her intensive areas of expertise." He further suggests "that many of the chapters contained in these volumes are the most incandescent, scholarly, and useful summary presentations of their subjects that have been crafted up to now." This type of braggadocio might seem presumptuous—prior to delving into the almost 6000 pages that constitute this preeminent work. In terms of depth and scale,<i>Principles and Practice of Ophthalmology</i>has two noble predecessors: Duke-Elder's<i>System of Ophthalmology</i>(published between 1958 and 1976) and Duane's<i>Clinical Ophthalmology</i>(Harper &amp; Row), a five-volume set that is regularly updated.<i>Principles</i>equals and outdoes these forerunners in consistency, quantity, and quality of illustrations and overall readability. No other contemporary
Non-nodal type of mantle cell lymphoma is a specific biological and clinical subgroup of the disease
Authors: C Royo, A Navarro, G Clot, I Salaverria, E Giné, P Jares, D Colomer, A Wiestner, W H Wilson, M C Vegliante, V Fernandez, E M Hartmann, N Trim, W N Erber, S H Swerdlow, W Klapper, M J S Dyer, M Vargas-Pabón, G Ott, A Rosenwald, R Siebert, A López-Guillermo, E Campo, S Beà
Journal: Leukemia (2012)
Continuous Emotional Support During Labor
Authors: Clifford M. Gevirtz
Journal: JAMA (1991)

<h3>To the Editor.</h3> —We read with interest the article by Kennell et al<sup>1</sup>concerning the efficacy of emotional support by<i>doulas</i>during labor in reducing both cesarean section rates and the use of epidural analgesia. We are concerned with the statistically significant difference in childbirth education afforded these patients. Was a truly informed consent obtained with full disclosure of the analgesia options available? While the study demonstrated decreased uses of cesarean sections and epidural analgesia, there is no documentation of patient satisfaction. Our experience has been that women who had "natural childbirth" with the first delivery and epidural analgesia with the second were markedly more satisfied with the latter. A longitudinal study with crossover comparing these methods would provide the answer. We would also emphasize that pain relief during labor accomplishes more than mere comfort for the parturient. Appropriate pain relief produces physiological and psychological effects that benefit both
Rare variants in CFI, C3 and C9 are associated with high risk of advanced age-related macular degeneration
Authors: Johanna M Seddon, Yi Yu, Elizabeth C Miller, Robyn Reynolds, Perciliz L Tan, Sivakumar Gowrisankar, Jacqueline I Goldstein, Michael Triebwasser, Holly E Anderson, Jennyfer Zerbib, David Kavanagh, Eric Souied, Nicholas Katsanis, Mark J Daly, John P Atkinson, Soumya Raychaudhuri
Journal: Nature Genetics (2013)
Concurrent thrombotic thrombocytopenic purpura and immune thrombocytopenic purpura in an HIV-positive patient: Case report and review of the literature
Authors: Lisa S. Yospur, Nora C.J. Sun, Priscilla Figueroa, Yutaka Niihara
Journal: American Journal of Hematology (1996)

Immune thrombocytopenic purpura (ITP) and thrombotic thrombocytopenic purpura (TTP) have each been associated with HIV infection. Sequential occurrence of these two diseases with a disease-free interval has been occasionally reported in the literature, whereas simultaneous manifestations of these two diseases have not been described. Here, we report an AIDS patient who was initially diagnosed as having TTP and showed an apparent partial response to plasmapheresis but was found to have a clinical course similar to ITP. Although precise mechanisms for the development of TTP and ITP in these patients are unclear, we offer several hypotheses. It is important to recognize that these two processes may be seen concurrently. © 1996 Wiley-Liss, Inc.
RADIUM THERAPY IN EYE DISEASE
Authors: A. Lawson, J. M. Davidson
Journal: BMJ (1910)

1THm present paper is an outcome of an investigation carried out by Mr. Mackenzie Davidson and myself into the possibilities of radium as a therapeutic measure in eye disease.We have carried on the work with the limited time at our disposal for over a year, and now venture to bring forward the results obtained, in the hope that they may stimulate further inguiry and research.A good many of the present cases were mentioned in a preliminry note published in vol.xxix of the Tran8actions ofthe Ophihalmological Society, but no statistical tables euch as are appended to this paper were made, and all the -cases are now grouped together and their special features detailed for easy inspeoction.We can endorse more fully now the opinion which we then ventured to express-namely, that radium is likely to
Copper deficiency and diet
Authors: Leslie M. Klevay
Journal: American Journal of Hematology (2007)

Copper Deficiency and DietTo the Editor: Harless et al. [1] reported two women with copper deficiency of unclear etiology whose deficiency quickly resolved after supplementation with copper gluconate.They suggested that consumption of 100 oz daily of soft drinks containing sucrose or fructose may have contributed to the problem because these simple sugars have been shown to disrupt copper utilization in animal experiments.A diet low in copper also may have been contributory.The Western diet often is low in copper [2], according to pooled data of more than 900 diets analyzed chemically and summarized in several articles.Recently, 62 and 36% of diets of 80 randomly selected adults in Baltimore, MD [3], were below the recommended dietary allowance (0.9 mg/day) and the estimated average requirement for adults (0.7 mg/day).The estimated average requirement is the median of a distribution of requirements; it applies only to apparently healthy people.Although soft drinks may have increased the copper requirements of the women, it seems unlikely that with body mass indices of 17 and 21 they had eaten sufficient copper from food when drinking 1400 kcal of Mountain Dew, or equivalent, daily.Recovery in a month from 2 mg copper gluconate daily (14.0%copper) yielding only 40% of the estimated average requirement is remarkable.
Culture of secrecy must be tackled
Authors: Michael V Williams
Journal: BMJ (2007)

The Royal College of Radiologists welcomes the chief medical officer's editorial on reducing harm from radiotherapy.1 In the five years to April 2006, only 211 incidents of a dose greater than intended were reported under the IR(ME) regulations.2 Many of these were correctable by adjusting subsequent treatment. Patient injury is a rare event; this is …
The changing epidemiology of lung cancer with a focus on screening
Authors: G. A Silvestri, A. J Alberg, J. Ravenel
Journal: BMJ (2009)

#### Summary points

Lung cancer is a global public health problem of epidemic proportions, and the number of people affected is expected to grow in the near future. Worldwide, in 2002 more than 1.3 million people were newly diagnosed with lung cancer.1 It is the leading global cause of death from cancer, and it accounts for 18% of all deaths from cancer and more than one million deaths a year since as far back as 1993.2 3 Lung cancer is the 10th leading overall cause of death, and it is expected to move to fifth place as its incidence rises in developing countries. Lung cancer is a disease that seems to fit the profile for a successful screening programme. However, developing an efficacious screening test that meets the established criteria for screening has proved elusive, despite evidence from many screening trials, and screening remains controversial. This review aims to shed light on the questions surrounding screening for lung cancer.

Active cigarette smoking is the main cause—it accounts for 85-90% of all lung cancers.2 w1-w5 In addition, exposure to secondhand cigarette smoke; pipe and cigar smoking; occupational exposure to agents such as asbestos, nickel, chromium, and arsenic; exposure to radiation, including radon gas in homes; and exposure to air pollution are all established …
Professionalism in Graduate Medical Education
Authors: Sanjay V. Desai, Aimee Zaas, Joel T. Katz
Journal: JAMA (2013)

Dr Arora and colleagues1 cited the need to shift the definition of professionalism from �nostalgic� to �new� to improve the well-being of trainees. While we agree that enhanced focus must be placed on physician health and team-based models of care, we caution that a core tenant of medical professionalism�an evidence basis for intervention�may have been overstepped.
Regional control of atrial fibrillation by rapid pacing in conscious dogs.
Authors: M Allessie, C Kirchhof, G J Scheffer, F Chorro, J Brugada
Journal: Circulation (1991)

BACKGROUND In five chronically instrumented conscious dogs, we studied the effects of rapid pacing on sustained electrically induced atrial fibrillation. METHODS AND RESULTS Twenty-three unipolar atrial electrograms were recorded simultaneously from the bundle of Bachmann and the lateral wall of the right and left atria. During sustained atrial fibrillation, the surface electrocardiogram showed continuous irregularities of the baseline without P or F waves as well as an irregular ventricular rhythm with narrow QRS complexes. The atrial electrograms showed rapid irregular activity with a median cycle length of 85 +/- 8 msec and a range (P5-95) of 33 +/- 18 msec. Overdrive pacing of atrial fibrillation was performed using symmetric biphasic rectangular stimuli (2-msec duration, sixfold that of threshold) applied to a pair of stimulating electrodes at the left atrial appendage. Stimulation was started at pacing intervals of about 10 msec longer than the local median fibrillation interval and subsequently shortened in steps of 1 msec. At a critical pacing interval slightly shorter than the median fibrillation interval, the atrium around the pacing site was suddenly captured by the electrical stimuli. The area of local capture had a diameter of 6.1 +/- 1.6 cm. The time window of capture was 12 +/- 4 msec. CONCLUSIONS These observations show that during electrically induced atrial fibrillation in chronically instrumented conscious dogs, a short excitable gap is present, permitting regional control of the fibrillatory process by rapid pacing.
Abstract 1916: Blockade of the fibroblast growth factor receptor (FGFR) system by the novel FGFR inhibitor BGJ398 modulates oncogenic signaling in human gastric cancer cells, endothelial cells and pericytes
Authors: Christian Moser, Christina Hackl, Hans J. Schlitt, Edward K. Geissler, Sven A. Lang
Journal: Cancer Research (2012)

Abstract Expression of the FGFR system has been associated with poor prognosis in patients suffering from gastric cancer. Moreover, activation of FGFRs has been demonstrated to mediate tumor angiogenesis through regulation of endothelial cell (EC) and pericyte motility and survival. Therefore, in this study we sought to investigate the effects of targeting FGFR on gastric cancer cells as well as on important components of the tumor microenvironment by the novel FGFR inhibitor BGJ398. For the experiments, human gastric cancer cell lines (TMK-1 and KKLS) as well as ECs and pericytes (vascular smooth muscle cells, VSMCs) were used. The FGFR inhibitor BGJ398 was provided by Novartis Oncology (Basel, Switzerland). Effects of BGJ398 on tumor cell growth and chemoresistance were determined by MTT assays. Impact of BGJ398 on motility of cancer cells was evaluated by modified Boyden chambers. Signaling pathways affected by BGJ398 treatment were assessed by Western blot analyses. To determine effects of FGFR blockade on ECs and pericytes conditioned media from gastric cancer cells was used. Results show that targeting FGFR by BGJ398 impaired growth of gastric cancer cells in a dose-dependent manner in vitro. Furthermore, activation of Akt and Erk in cancer cells was effectively inhibited while expression of c-Myc and HIF-1α was substantially reduced. Additionally, therapy with BGJ398 led to significant inhibition of constitutive migratory and invasive properties of gastric cancer cells (P&amp;lt;0.05). Interestingly, interference with FGFR by BGJ398 increased sensitivity for chemotherapy with oxaliplatin and 5-FU in tumor cells. In ECs as well as pericytes blockade of FGFR by BGJ398 significantly inhibited cell growth and motility even upon stimulation with conditioned media (P&amp;lt;0.05). In conclusion, inhibition of the FGFR system by BGJ398 disrupts oncogenic signaling, impairs tumor cell motility and improves chemosensitivity in gastric cancer. Furthermore, antiangiogenic effects might be mediated via direct effects on ECs and pericytes. Hence, targeting the FGFR system may represent a promising approach to improve current therapy strategies for gastric cancer and warrants further preclinical evaluation. 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 1916. doi:1538-7445.AM2012-1916