tbuckley/cabot-search huggingface dataset:
Abstract 5411: Development of SCLC specific nanoparticle-mediated therapeutic gene delivery
Authors: Chandrashekhar D. Kamat, Ron B. Shmueli, Joel C. Sunshine, Nick Connis, Jordan J. Green, Christine L. Hann
Journal: Cancer Research (2011)

Abstract Lung cancer is the most common cause of cancer-related deaths worldwide. Small cell lung cancer (SCLC) is a particularly aggressive form of lung cancer characterized by early metastatic behavior. Even with currently recommended therapy, the average survival of SCLC patients is less than 1 year. There is an urgent need for novel treatments. The majority (70-90%) of SCLC cases possess alterations in p53 and Rb. This relative genetic homogeneity makes SCLC an attractive context in which to develop and test novel gene therapy approaches. We have initiated studies using non-viral, poly-β amino acid ester (PBAE) nanoparticle delivery of gene therapy in SCLC. PBAE polymers possess numerous advantages over viral delivery systems such as structural diversity, cost effectiveness, low immunogenicity and higher stability. PBAEs encapsulate DNA to form biodegradable cationic nanoparticles and have been studied in a variety of cancer cell types and in primary endothelial cells. This is the first study of PBAEs in SCLC. A PBAE polymer library was screened in two SCLC lines using a luciferase-based high-throughput screen (HTS). Thirty-two of 112 polymers were further characterized in the H446 SCLC cell line using a CMV-GFP reporter construct and analyzed by qualitative (microscopy) and quantitative (flow cytometry) methods. This secondary screen revealed that the polymers had variable transfection efficiencies ranging from 8-55%. Four polymers, 446LG, 447LG, 456LG and 457 exhibited high transfection efficiencies (42-55%) in two SCLC cell lines, including one suspension line. Using PBAEs complexed with Cy5-labeled DNA, we were able to demonstrate that &amp;gt;90% cells bind and internalize the nanoparticles. We have initiated studies to better elucidate bottlenecks between nanoparticle uptake and gene expression. Additionally, preliminary studies in tumor-bearing athymic nude mice demonstrated gene uptake and expression via intratumoral injection of 457 and 446LG polymer/DNA complexes. Ongoing studies include further optimization of PBAEs for in vitro gene expression and systemic in vivo delivery. In parallel, we are performing genetic characterization of patient-derived primary SCLC xenografts to verify relevant gene targets. Taken together, our data supports further development of a non-viral PBAE-based gene delivery approach in SCLC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5411. doi:10.1158/1538-7445.AM2011-5411
748. Requirements for Microtubule-DNA Interactions during Cytoplasmic Trafficking of Plasmids
Authors: Erin E. Vaughan, David A. Dean
Journal: Molecular Therapy (2006)

Relatively little is known about how naked DNA moves through the cytoplasm to the nucleus during transfections and other forms of gene delivery. It has been suggested that the dense latticework of the cytoskeleton impedes free diffusion of DNA, implying that plasmids would be unable to reach the nucleus. However, transfections do work, and thus there must be mechanisms by which DNA circumvents cytoplasmic obstacles. We have previously shown that in adherent cells after electroporation or microinjection, plasmid DNA requires intact microtubules to reach the nucleus. Further, we have demonstrated that inhibition of dynein impedes the ability of the plasmid to reach the nucleus. However, it remains unknown how plasmids interact with dynein and hence microtubules. In our past studies, all of the DNA used contained a promoter, a reporter gene and a downstream DNA Targeting Sequence (DTS). A DTS is a sequence in the DNA that is known to bind transcription factors. The transcription factors contain nuclear localization sequences (NLS) that facilitate nuclear import of the protein-DNA complex that is formed in the cytoplasm during transfection. One possible mechanism for cytoplasmic trafficking of transfected plasmids is that after microinjection or electoporation of adherent cells, the DTS on the plasmid is bound by transcription factors and it is via these transcription factors that the plasmid interacts with dynein and is transported to the nucleus via microtubules. Alternatively, a more general mechanism may occur, whereby factors that bind to any type of DNA (i.e. plasmids not containing a DTS) bind non-specifically to the plasmid, creating a different complex that mediates interaction between the plasmid and dynein. In order to test which of these possibilities is occurring, we used an in vitro microtubule spin-down assay. Plasmid, either with or without a DTS, was added to microtubules in the presence of cell extract and separated by centrifugation. Only plasmids that interact with microtubules should be found in the microtubule-containing pellet. As an alternative approach to the biochemical assays, fluorescently labeled PNA-DNA with and without a DTS was cytoplasmically microinjected and followed in real time to further determine if the DTS plays a role in trafficking to the nucleus. Our results suggest that the DTS facilitates an increased interaction between the microtubules and plasmid. These results are important in elucidating how naked DNA reaches the nucleus and an understanding of this process is imperative to improving the efficiency of gene transfer.
Prevention of Type I Diabetes and Recurrent β-Cell Destruction of Transplanted Islets*
Authors: Robert H. Slover, George S. Eisenbarth
Journal: Endocrine Reviews (1997)

I. Introduction II. Disease Pathogenesis III. Disease Prediction A. Genetic prediction B. Immunological prediction C. Metabolic prediction IV. Prevention of Type I Diabetes A. Trial design B. Genetic prevention C. Prevention: preautoimmunity D. Prevention: postautoimmunity/prediabetes E. New onset patients/prevention of further β-cell destruction F. Pancreas and islet cell transplantation/prevention of recurrent diabetes G. Islet cell transplantation/prevention of β-cell destruction V. Conclusion
Mantle cell lymphoma. A clinicopathologic study of 68 cases from the Nebraska Lymphoma Study Group
Authors: Dennis D. Weisenburger, Julie M. Vose, Timothy C. Greiner, James C. Lynch, Wing C. Chan, Philip J. Bierman, Bhavana J. Dave, Warren G. Sanger, James O. Armitage
Journal: American Journal of Hematology (2000)

Although mantle cell lymphoma (MCL) is considered a distinctive disease entity within non-Hodgkin's lymphoma (NHL), the cytology and growth pattern of MCL can be quite variable and the clinical significance of these features is unclear. Also, the role of anthracyclines in the management of MCL is unclear. Therefore, we examined our experience with MCL in an effort to clarify these important issues. We identified 68 patients with MCL who were evaluated clinically and treated by the Nebraska Lymphoma Study Group. Treatment consisted of combination chemotherapy containing an anthracycline in 76% of the patients. The cases were grouped by blastic or lymphocytic cytology, and the latter were divided by growth pattern into nodular (or mantle-zone) and diffuse types. The clinical and pathological variables were then evaluated for their prognostic value. The median overall survival (OS) and failure-free survival (FFS) for the entire group were 38 months and 12 months, respectively, and there was no survival advantage for those who received an anthracycline. The cases were grouped as follows: blastic type, 26%; nodular lymphocytic type, 44%; and diffuse lymphocytic type, 30%. Both the cytology and pattern of growth were predictive of OS and FFS. The median OS was as follows: blastic type, 55 months; nodular lymphocytic type, 50 months; and diffuse lymphocytic type, 16 months (P = 0.0038). The clinical features that predicted for a shorter survival included bone marrow involvement, advanced stage disease, B symptoms, a poor performance score, and the International Prognostic Index. We conclude that new therapeutic approaches, with the patients stratified by histologic type and clinical prognostic factors, are clearly needed for MCL. Am. J. Hematol. 64:190–196, 2000. © 2000 Wiley-Liss, Inc.
Effect of potassium cardioplegia on myocardial ischemia and post arrest ventricular function.
Authors: H V Schaff, R Dombroff, J T Flaherty, B H Bulkley, G M Hutchins, R A Goldman, V L Gott
Journal: Circulation (1978)

To assess the effects of moderate potassium cardioplegia (37 mEq/l KCl) on the severity of myocardial ischemia during arrest and on post arrest ventricular function, 32 isolated, isovolumic feline hearts were studied before, during and 1 hour after ischemic arrest. Normothermia (37 degrees C) was maintained in the remaining 16 hearts, eight without KCl and eight with KCl. Hypothermia (27 degrees C) was maintained in the remaining 16 hearts, eight with KCl and eight without KCl. Myocardial oxygen (PmO2) and carbon dioxide tensions (PmCO2) were measured by mass spectrometry. Maximum developed intraventricular pressure (max DP) and max dP/dt were used as indices of performance. Compared with normothermic or hypothermic arrest alone, the addition of potassium cardioplegia resulted in a significant reduction in the peak PmCO2 measured during the arrest period. Hypothermia alone resulted in morphologic evidence of improved myocardial preservation and a significant reduction in peak PmCO2 compared with normothermia. Post arrest ventricular function was best with the combination of hypothermic arrest and potassium cardioplegia (max DP = 96 +/- 6% of control and max dP/dt = 99 +/- 5% of control). These data suggest that the beneficial effects of postassium cardioplegia and 27 degrees hypothermia are additive, and that reduction in myocardial ischemia as evidenced by a reduction in peak PmCO2 correlated with improvement in ventricular performance in the post arrest period and with preservation of myocardial structure.
937. Radioprotection of Normal Tissue Cells by Transfer of the Human Superoxide-Dismutase Gene
Authors: Marlon R. Veldwijk, Carsten Herskind, Stephanie Laufs, W. Jens Zeller, Stefan Fruehauf, Frederik Wenz
Journal: Molecular Therapy (2006)

Background: Protection of normal tissue against radiation- induced damage would increase the therapeutic ratio of radiotherapy. A promising strategy for this approach is gene therapy-mediated overexpression of copper-zinc (CuZnSOD) and manganese superoxide-dismutase (MnSOD). Recombinant adeno-associated virus 2 (rAAV2) are attractive vectors owing to their ability to infect non-dividing cells and a very low risk of insertional mutagenesis. The purpose was to test the radio-modulating effects of SOD on human primary lung fibroblasts (HPLF). Methods: Low passage HPLF (MRC5) cells were transduced with the rAAV2-SOD vectors, harvested on day 3, irradiated (1-8 Gy) and analysed using FACS, western blot, SOD-activity and colony formation assays. Results: High transduction rates were obtained with >80% of the HPLF cells expressing the respective SOD. Compared to transduction controls, CuZnSOD did not exhibit any radioprotective effects, whereas for MnSOD-transduced HPLF an increase of approximately 30% in the survival of colony-forming cells was observed (1-4 Gy). Conclusion: An increase in clonogenic survival (1.3-fold) of HPLF cells after transfer of MnSOD and subsequent irradiation was shown. Earlier, we have shown lack of protection in tumour cells (HeLa), thus supporting that MnSOD may increase the therapeutic ratio. rAAV2 vectors are promising tools for the delivery of radioprotective genes in normal tissue such as the lung for pulmonary or intestine cells for prostate irradiation.
Simultaneous Transmission/Emission Myocardial Perfusion Tomography
Authors: Edward P. Ficaro, Jeffrey A. Fessler, Paul D. Shreve, James N. Kritzman, Patricia A. Rose, James R. Corbett
Journal: Circulation (1996)

Background The purpose of the present study was to assess the diagnostic performance of attenuation-corrected (AC) stress 99m Tc-sestamibi cardiac single-photon emission computed tomography (SPECT) for the identification of coronary heart disease (CHD). Methods and Results With a triple-detector SPECT system with a 241 Am transmission line source, simultaneous transmission/emission tomography (TCT/ECT) was performed on 60 patients with angiographic coronary disease and 59 patients with ≤5% likelihood of CHD. Iteratively reconstructed AC stress 99m Tc-sestamibi perfusion images were compared with uncorrected (NC) filtered-backprojection images. Normal database polar maps were constructed from AC and NC images for quantitative analyses. From the low-likelihood patients, the visual and quantitative normalcy rates increased from 0.88 and 0.76 for NC to 0.98 and 0.95 for AC ( P &lt;.05). For the detection of CHD, the receiver operating characteristic curves for the AC images demonstrated improved discrimination capacity ( P &lt;.05), and sensitivity/specificity values increased from 0.78/0.46 (NC) to 0.84/0.82 (AC) with visual analysis and from 0.84/0.46 (NC) to 0.88/0.82 (AC) with quantitative analysis. For localization of stenosed vessels, visual and quantitative sensitivity values were 0.51 and 0.63 for NC and 0.64 and 0.78 for AC images ( P &lt;.05), respectively. Conclusions TCT/ECT myocardial perfusion imaging significantly improves the diagnostic accuracy of cardiac SPECT for the detection and localization of CHD. Clinical use of TCT/ECT imaging deserves serious consideration.
Abstract P6-07-13: Local relapse and survival
Authors: R Harland, P Prathap, A Lionaki, N Mahmood
Journal: Cancer Research (2012)

Abstract Aim: Local recurrence may precede distant relapse and death. Many factors which predict local recurrence also predict death. Few studies have investigated the contribution of local recurrence to mortality independent of prior prognostic factors such as nodal status. We wished to estimate the extent to which overall survival is affected specifically by local recurrence. Methods: 114 of of 2945 patients aged 19 to 94 years (mean 58.3) who had either mastectomy or breast conservation for breast cancer between 1991 and 2011 subsequently suffered an ipsilateral local recurrence. We matched, with one exception (due to extreme young age), each patient who had a local recurrence with 2 controls matched for calendar year of presentation, age, nodal status, grade, and tumour size. A Cox regression analysis of survival from the first therapeutic operation was done on the case matched subset with local recurrence coded dichotomously and age coded continuously as the absolute deviation from the population mean (as both young and old age affect survival adversely) as predictors. To confirm independence of the effect of local recurrence on the hazard of death a further Cox regression analysis of survival as above was done for the whole series with local recurrence, Grade 3, &amp;gt;3 nodes involved, tumour diameter &amp;gt;40mm, coded dichotomously, and age coded as above as independent variables. Results: The results of the analyses are given in the table below. The estimate of hazard of death associated with local recurrence was similar in both analyses suggesting minimal confounding effect. As expected large tumour size, high grade and heavy nodal involvement predicted survival independently. Conclusion: Local recurrence was associated with only a modest increase of about 50% in the hazard of death independent of tumour stage, size and grade which remained the most significant predictors within this model. Extremes of age were associated with increasing hazard of death and should be similarly coded when analysing unadjusted survival. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-07-13.
Poly(ethylene glycol)–poly(l-lactide) diblock copolymer prevents aggregation of poly(l-lactide) microspheres during ethylene oxide gas sterilization
Authors: Yongdoo Choi, Sang Yoon Kim, Myeong-Hee Moon, Sun Hee Kim, Kwang-Sun Lee, Youngro Byun
Journal: Biomaterials (2001)
The Kansas Hypnotism Case.
Authors: John Madden
Journal: JAMA (1895)

Milwaukee, Wis., May 31, 1895. <h3>To the Editor:</h3> —Some time ago the secular press published a statement to the effect that the Supreme Court of Kansas had recognized a plea of hypnotism as a defense in a trial for homicide. Since then the statement has been reiterated, not only in a great many newspapers, but in some of the medical journals as well. The statement is entirely untrue. The facts in the case are these: one Gray incited McDonald, an employe of the former, to kill a man named Patton, also an employe of Gray. McDonald was tried in the lower court and the defense sought to prove that Gray's influence over McDonald was exerted through hypnotic power; and the judge of the lower court allowed the introduction of expert testimony to establish this fact. McDonald was acquitted by the jury in the lower court; so his case did not
Contemporary Management of Impotence and Infertility
Authors: Anthony J. Thomas
Journal: JAMA (1989)

<i>Contemporary Management of Impotence and Infertility</i>is, as its title suggests, two small texts in one binding. It offers a concise, up-to-date summary of the recent developments in the diagnosis and management of erectile dysfunction as well as male factor infertility. As I read the text in preparation for this review, I had a recurrent sense of<i>déjà vu</i>and soon realized that much of the information contained herein was previously published in two past issues of the<i>Urologic Clinics of North America</i><sup>1,2</sup>by many of the same authors. If, however, repetition is indeed the mother of learning, the reader can learn from what is said in this book. Over the past few years, Dr Tom Lue and his colleagues at the University of California, San Francisco, have made significant contributions to our understanding of erectile function. Dr Lue's writing style and corrosion cast photographs allow even the novice
Heroin and cannabis use is declining but new drugs show increase, says EU report
Authors: R. Watson
Journal: BMJ (2014)

The use and availability of heroin in Europe seems to be declining, the Lisbon based European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) has said. In its latest annual report, released on 27 May, it noted that the number of reported first time entrants for specialist drug treatment for heroin problems fell from a peak of 59 000 in 2007 to 31 000 in 2012.1

Similarly, although cocaine remained the most commonly used illicit stimulant in Europe, recent data showed that its use was also declining, especially among 15-34 year olds. And after a peak in 2008 notable decreases had occurred …
Length of a lippes loop.
Authors: D H Bailey
Journal: BMJ (1969)

I wish to report an unusual complication associated wit the insertion of a Lippes loop.  A presterilized Lippes loop size D in a 1-unit-sized pack was inserted into a multigravid patient according to the instructions - that is the loop was pulled into the inserting tube only within a minute of insertion.  Before insertion it had been noted that the loop within the packet appeared to conform to the normal dimensions of the loop size D - that is 30 mm. long by 30 mm. wide.  After half the loop had been inserted into the patient there was severe pain and a small amount of bleeding so that the loop and inserter were withdrawn.  At no time had the insertion of the loop been associated with a sense of giving way as would possibly occur if the myometrium was penetrated.  The patient was hospitalized for 24 hours ther was no bleeding and no pain.  Closer investigation of the loop within 5 minutes of withdrawal of the loop from the patient disclosed that it had changed its dimensions.  It still conformed to the 30 mm. width but the various angles had opened out and the new length had become 50 mm.  Two days later this length had remained at 50 mm.  I would like to suggest that it might well be in future a wise precaution for the loop to be not only drawn into the tube as suggested before insertion but withdrawn into the tube and expelled at least once to see if it takes up its pre-tube  length rapidly before use on the patient.(Full text)
NIH website of original research to start in January
Authors: T. Delamothe
Journal: BMJ (1999)

The US National Institutes of Health has announced that its web based repository of original research in the life sciences will “go live” in January 2000, just 10 months after the idea was floated by the institute's director, Harold Varmus (20 March, p 784).

The repository, to be called PubMed Central, will provide free access to both peer reviewed and non-peer reviewed articles submitted by existing …
Asylum seekers in Bangladesh face humanitarian crisis
Authors: P. Moszynski
Journal: BMJ (2010)

Concern is mounting over the fate of thousands of unregistered refugees from Burma after a series of violent crackdowns by the Bangladeshi authorities. Last week the charity Medecins Sans Frontieres urged immediate action to deal with the humanitarian crisis.

The refugees are members of a Bengali speaking Muslim minority, the Rohingya, from northeastern Myanmar (Burma). In recent years more than 200 000 Rohingya have fled to Bangladesh to escape violence and persecution.

However, only about 10% are officially acknowledged as refugees, so most are effectively stateless and are currently facing forcible repatriation, says a new report by Medecins Sans Frontieres. The report calls for an immediate end to the violence, along with …
LIPOPROTEIN-PHOSPHOLIPASE A2 IS ASSOCIATED WITH ABNORMAL DIGITAL REACTIVE HYPEREMIA AND IMPAIRED CORONARY FLOW RESERVE IN PATIENTS WITH STABLE CORONARY ARTERY DISEASE
Authors: Ignatios Ikonomidis, John Lekakis, Paraskevi Trivilou, Vlassis Tritakis, Stavros Tzortzis, Charalambos Koukoulis, Kostas Kontsas, Maria Anastasiou-Nana
Journal: Journal of the American College of Cardiology (2011)
Murine cytomegalovirus-associated pneumonitis in the lungs free of the virus.
Authors: K Tanaka, Y Koga, Y Y Lu, X Y Zhang, Y Wang, G Kimura, K Nomoto
Journal: Journal of Clinical Investigation (1994)

At 4 wk after intraperitoneal inoculation of murine cytomegalovirus (MCMV) in adult BALB/c mice, MCMV remained detectable only in the salivary glands. When T cells of these mice were activated by a single injection of anti-CD3 epsilon monoclonal antibody, mice died of interstitial pneumonitis at 24-48 h after injection, accompanied by elevation of serum levels of TNF-alpha and IFN-gamma. However, MCMV remained undetectable in the lungs during the period. Simultaneous injection of cyclosporin A reduced such effects of anti-CD3. In conclusion, although the presence of MCMV in the host may be required, MCMV-associated pneumonitis is not mediated by virus in the lung but probably by the cytokines released from T cells, of which responsiveness to stimulation via CD3 molecule has been presumably modified by MCMV infection.