tbuckley/cabot-search huggingface dataset:
Targeting the Akt / NF-kappa B pathway by lidamycin leads to inducing apoptosis and cell cycle arrest in human pancreatic cancer cells and inhibiting the xenograft growth in nude mice
Authors: Chen Jing
Journal: Cancer Research (2007)

3218   As previously reported, K-ras mutations have been found in up to 90% of pancreatic cancers. Expression of mutant K-ras can activate the Akt / protein kinase B pathway, resulting in the activation of the nuclear factor-κB (NF-κB) transcriptional factor. Up-regulated constitutive NF-κB activity plays a key role in pancreatic carcinoma. Activation of NF-κB may relate to the resistance of cancer cells in response to chemotherapeutic agents. Lidamycin (C-1027) is an enediyne-containing antitumor antibiotic with extremely potent cytotoxicity to cancer cells. In the present study, the effect of lidamycin on established pancreatic cancer cell lines including PANC-1 and SW1990 were investigated. Determined by Western blot analysis, lidamycin displayed a dose-dependent inhibition of phospho-Akt and NF-κB activation with a minimum effective concentration of 1 nM. Moreover, down-regulation of K-ras mRNA and protein expression by lidamycin was observed in both cell lines as determined by RT-PCR and Western blot analysis. By MTT assay, PANC-1 and SW1990 cells were highly sensitive to lidamycin with the IC50 values 0.955±0.414 nM and 0.426±0.212 nM, respectively. In terms of IC50, the cytotoxicity of lidamycin was much more potent than that of doxorubicin (451±14 nM and 2017±28 nM), gemcitabine (1874±168 nM and 3724±143 nM), mitomycin (4240±162 nM and 5082±148 nM), and taxol (578±85 nM and 603±42 nM). Determined by flow cytometry, lidamycin caused a significant increase of apoptotic cells and a cell cycle G2/M arrest in both PANC-1 and SW1990 cell lines. In addition, lidamycin-treated cells showed nuclear apoptotic morphology with the DNA-specific dye Hoechst 33342 staining. Examined by transwell cell migration chamber assay, lidamycin inhibited the migration and invasion of PANC-1 and SW1990 cells through an extra-cellular matrix. By zymography, lidamycin inhibited MMP-9 activity that may be related to the reduction of the invasive potential of pancreatic cancer cells. Furthermore, lidamycin was found to suppress tumor growth of SW1990 xenografts in athymic nude mice. At the doses of 0.02 mg/kg and 0.04 mg/kg (iv, once a week for two weeks) lidamycin inhibited the growth of xenografts by 66% and 72% ( P
Electrophoretic and Morphologic Studies of a Transplantable Reticulum-Cell Neoplasm in Mice Inducing Amyloidosis&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: R. Rask-Nielsen, H. E. Christensen, J. Clausen
Journal: JNCI Journal of the National Cancer Institute (1960)

The first 10 transfer generations of a reticulum-cell neoplasm of the mouse constantly associated with the development of amyloidosis are described. Microscopic examination revealed that the grafts were pyroninophilic, plasma-cell differentiated reticulum-cell sarcomas, spreading diffusely, especially to the lymph nodes, liver, and spleen. Serum-protein changes observed in paper electrophoresis and immuno-electrophoresis were a hypergamma-globulinemia changing to an increase in the β- (β2-III) and α2-fractions (α2-I and 2-II) and eventually to a reduction in albumin and β-globulin and a further increase in the α2-fraction (α2-III and 2-V); the latter changes were accompanied by urinary excretion, particularly of albumin and β-globulin (β2-I). During tumor growth a relative and often an absolute granulocytosis and monocytosis were seen. Amyloid development first was found, most frequently and markedly, in the spleen, then in the liver, in the kidneys, and, occasionally, in many other organs. Mice with the longest survival time showed the heaviest degree of amyloidosis. Our findings indicated that amyloidosis was due to a persistent hyperimmunization, in accordance with the theory of the pathogenesis of amyloidosis advanced by Teilum. The last stage of the serum-protein changes and the urinary elimination of protein were explained as caused by the development of a nephrotic syndrome caused by renal amyloidosis. In mice with a short survival time and extensive tumor growth without amyloidosis, a paraprotein-like γ-protein was found in serum and the tumors showed a more plasma-cell differentiated picture.
Economic impact analysis of a tele-medicine program to improve the quality of apirometry in primary care
Authors: Nuria Marina, Elena Lopez de Santa Maria, Asuncion Gutierrez, Juan Carlos Bayon, Larraitz García, Juan B. Galdiz
Journal: European Respiratory Journal (2012)

Introduction: The tele-spirometry (TS) procedure consists in a computer application ( espiro.osasunet ) which allows the control and improvement of the quality of the spirometry (S) carried out in primary care centers (PCC), leading a continuous training of professionals that perform the technique.

Aim: To calculate the economic impact of a procedure of TS in the Basque Health Service.

Methods: The study was based on the impact in the funder of the Public Health System and a time horizon of 5years: 2010-2014.We compared the TS with the usual procedure and calculated the direct costs of the test, the computer platform, training and staff for their handling. The population was calculated using the prevalence of COPD in Spain (Soriano ERJ 2009). Effectiveness was measured as the average of S with quality A+B (ATS).

Results: The COPD population who will perform a S goes from 32.850 to 35.207 (2010-2014). At present (2011) 53 PCC have been involved and 1500 S have been done. At the end of 2014, 275 will be included and, with inicial data (Marina 2011 ERS Congress) 35000 S will be done yearly. The cost of one S for the procedure of TS, in 2010, was 48,17€ with an effectiveness of 83%; while for the usual procedure was 37,95€ and 57%. The budget impact analysis, at the end of the year 2014, reflected a decrease of 132.438€, with the assumption that the S of poor quality should be repeated.

Conclusions: The TS procedure involves an increase in the initial budget but produces a saving of the 6.3% (€132.438) in the medium term. For subsequent studies we will have to know the economic impact that this improvement in the quality of the S may have on the diagnosis and prognosis of COPD patients.
CUTANEOUS RESPIRATION IN MAN
Authors: A. Carlton Ernstene, Marie C. Volk
Journal: Journal of Clinical Investigation (1932)

Shaw and his associates (1, 2) demonstrated that the rate of cutaneous respiration in man is influenced principally by the temperature and humidity of the air in contact with the skin and by individual character- istics of different subjects.The present investigation was undertaken to establish the range of carbon dioxide elimination and oxygen absorption through the skin in normal individuals of various ages under controlled conditions of temperature and relative humidity.
Cardiac Imaging: A Companion to Braunwald's Heart Disease
Authors: Melvin L. Marcus, Eugene Braunwald
Journal: Annals of Internal Medicine (1991)

This work is designed to function as the medical imaging companion to the third edition of Dr Braunwald's Heart Disease. It reviews 10 major areas of imaging in detail, including pathophysiology. The contributors compare each of the standard and evolving cardiac imaging techniques.
Intensive care medicine comes of age
Authors: N. Soni, D. Wyncoll
Journal: BMJ (1999)

Lord Nuffield is reputed to have said, “Anyone can give an anaesthetic and that is the problem.” This could equally well have been said of intensive care medicine over the past 30 years—a specialty without a home and until recently without a recognised training in the United Kingdom. This summer, however, intensive care medicine was recognised in both the UK and Europe under the European specialist medical qualification regulations. Other countries have established training programmes in intensive care medicine, but the UK's is unique in that a multidisciplinary group planned the training for a multidisciplinary specialty. The establishment of the specialty thus holds lessons for other emerging multidisciplinary specialties—and it may have wider benefits for the parent specialties.

The basis of intensive care medicine is wide, incorporating skills from many …
Abstract IA30: Combined targeted therapies, where to next
Authors: Georgina V. Long
Journal: Cancer Research (2015)

Abstract Combined BRAF and MEK inhibition has improved patient outcomes beyond single agent BRAF inhibition in BRAF-mutant metastatic melanoma, however 25% of patients do not have a RECIST-response and 30% progress within six months. Analysis of melanoma progressing metastases from combination-treated patients reveals that early resistance via the MAP kinase pathway is more common than that observed with single agent BRAF inhibition, which raises the questions of whether even stronger MAP kinase pathway inhibition would be of benefit to patients, and whether this is achievable therapeutically. However, the combination of MAP kinase inhibitors with immunotherapy may be a more effective strategy. Preliminary results in human tissues suggest that the presence of tumor-infiltrating lymphocytes and tumor-cell PDL1 expression may assist in patient selection for such a strategy. Early-during treatment responding metastases from combined BRAF and MEK inhibition-treated patients demonstrate similar levels of tumor-infiltrating lymphocytes as observed with single agent BRAF inhibition, suggesting that MEK inhibitors may not negatively impact the immunogenicity of targeted therapy early-on, and supports the concept that concurrent targeted- and immuno-therapy strategies may provide a greater opportunity for disease control than in sequence. Citation Format: Georgina V. Long. Combined targeted therapies, where to next. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Melanoma: From Biology to Therapy; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(14 Suppl):Abstract nr IA30.
A national database for co-morbidity in RA to evaluate drug safety. Solid cancers in RA and following anti-TNF treatment
Authors: J Asking, L Brandt, L Bertilsson, N Feltelius, M Fored, P Geborek, L Jacobsson, S Lindblad, J Lysholm, Solbritt Rantapää Dahlqvist, T Saxne, L Klareskog
Journal: Annals of the Rheumatic Diseases (2004)

A national database for co-morbidity in RA to evaluate drug safety. Solid cancers in RA and following anti-TNF treatment
Abstract 19818: Improving Radiation Safety in the Cardiac Catheterization Laboratory - a Quality Improvement Initiative
Authors: Alina M Robert, James T DeVries, John E Jayne, John B Weaver, Sheila M Conley, William C Burke, Donald F Guadagni, Aaron V Kaplan, Bruce D Hettleman, Bruce J Friedman, Nathaniel W Niles, John F Robb, David J Malenka
Journal: Circulation (2014)

Introduction:  Cardiovascular imaging and interventions account for 40% of total medical radiation exposure (excluding radiation therapy). Exposure to ionizing radiation may cause skin injuries or increased risk of cancer and genetic defects.   Hypothesis:  Changing fluoroscopy defaults to low dose and low frame rate, while maintaining the option to use higher settings when needed, would decrease average patient radiation dose during cardiac catheterization without compromising procedural success.   Methods:  In 5/2013 we changed fluoroscopy defaults in 1 of 4 cardiac catheterization laboratories to lower dose (600 nGy/sec from 660 nGy/sec to the detector), lower frame rate (7.5 frames/sec from 15 frames/sec) and lower maximum patient exposure (5 Rad/min from 10 Rad/min). We recorded the air kerma (AK) in mGy/case for 719 coronary angiograms (448 pre, 271 post intervention) and 730 coronary interventions (451 pre, 279 post intervention) performed in this laboratory from 6/12-12/13. We used statistical process control analysis to evaluate changes in average monthly AK and to assess for statistical significance.   Results:  Following fluoroscopy default changes, average AK/case decreased by 21.2% for coronary angiograms (1282.1 ± 857.7 pre vs 1010.9 ± 846.4 post) and by 17.7% for coronary interventions (2858.6 ± 1802.9 pre vs 2353.6 ± 1210 post). After 5/13 there was a significant reduction in average monthly AK with a value below the 3 sigma line in 10/13 for coronary angiograms, and 2 consecutive values below the 2 sigma line in 11/13 and 12/13 for coronary interventions. There were no temporal changes in the incidence of adverse outcomes for interventions.   Conclusions:  Utilizing low fluoroscopy dose and frame rate defaults can significantly decrease exposure to ionizing radiation for patients undergoing cardiac catheterizations without affecting procedural success.
Depression management clinics in general practice?
Authors: T. Kendrick
Journal: BMJ (2000)

General practice p 550

In 1979 Stott and Davis identified the four areas of exceptional potential to serve patients in every primary care consultation, which included management of continuing problems along with management of the presenting problem, opportunistic health promotion, and modification of help seeking behaviour.1 However, we now know that chronic diseases are often more effectively managed through special clinics outside routine consultations, usually staffed by practice nurses. Such “mini-clinics” have been shown to improve the outcome of asthma2 and diabetes3 and are now widespread in British general practice, encouraged by separate payments for chronic disease management. Might this approach also be applied to depression?

For many patients depression is more accurately considered a chronic relapsing condition, rather than a series of discrete episodes, and, as for other chronic conditions, there are concerns about how it is managed in routine consultations. Leaving …
Universal Health Coverage
Authors: Brian Vastag
Journal: JAMA (2004)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Lowering Risk of Second Malignancy in the Survivors of Childhood Cancer
Authors: M J Friedrich
Journal: JAMA (2001)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract P375: Contemporary Rates and Predictors of Death in Adults with Warfarin-Associated Bleeding Treated with Plasma: The REVERSAL Study
Authors: Alan S Go, Thomas K Leong, Ulla M Forssen, Douglas M Watson, Sue Hee Sung, Teresa N Harrison, Kristi Reynolds
Journal: Circulation (2015)

Background:  Warfarin increases the risk of bleeding that is frequently treated with plasma for acute reversal in the setting of life-threatening hemorrhage. However, limited contemporary data exist about the risk and predictors of death in the first 45 days after treatment with plasma.   Methods:  We conducted a retrospective cohort of all adult members in Kaiser Permanente Northern and Southern California, two integrated healthcare delivery systems caring for >6.8 million persons who received plasma for acute warfarin reversal in the setting of major bleeding between 2008-2013. We identified deaths from any cause during the first 45 days after receipt of plasma based on comprehensive health plan databases, Social Security Administration vital status files and state death certificates. Data on patient demographics, comorbidities and baseline medication use was ascertained from health plan administrative, inpatient and outpatient diagnosis and procedure, lab and pharmacy databases. We used multivariable logistic regression to identify independent predictors of death.   Results:  Among 4509 adults who received plasma for acute warfarin reversal in the setting of major bleeding, mean (SD) age was 75 (11) years, 56% were women, 11% were black, 12% were Asian and 15% Hispanic. Thirty-nine percent of bleeds were intracranial, 57% gastrointestinal and 5% other major extracranial. There was a high prevalence of pre-existing morbidity, including 42% heart failure, 87% hypertension, 38% diabetes, 84% dyslipidemia and 38% chronic lung disease. During the first 45 days after receipt of plasma, 15.2% (95% CI: 14.2%-16.3%) of patients died from any cause. Multivariable predictors of death are shown in the Table.   Conclusions:  Among a large, diverse, contemporary population of patients receiving plasma for acute warfarin reversal for major bleeding, >15% died in the first 45 days. Type of bleed, degree of over-anticoagulation, and selected demographic and clinical characteristics can identify patients at higher risk for early death.
223. Delivery of HSV Based Vectors for Correction of CNS Pathology in Mucopolysaccharodosis Type vii (MPS vii)
Authors: Srikanth Yellayi, Bradford Berges, John Wolfe, Charles Vite, Nigel Fraser
Journal: Molecular Therapy (2004)

Current gene therapy strategies targeting the CNS involve multiple and cumbersome modes of delivery. In the current study we used a neuroattenuated Herpes simplex −1 (HSV-1/1716-LAT-hGUSB) containing beta glucuronidase (GUSB) driven by the latency associated transcript (LAT) promoter and lacking the ICP 34.5 gene. We analyzed the sites of expression of the transgene activity as well as the latent viral vector after delivering the recombinant vector into the cerebrospinal fluid by injection of 3 × 105 PFU/10 μl into the cisterna magna of C3H HeOuJ mice (4 weeks old). Our study showed that there is significant expression of the transgene after 4 weeks post-injection in mice injected with the 1716-LAT-hGUSB recombinant virus compared to control mice injected with the 1716 parental strain virus. The expression of the transgene declined after 4 weeks, but was still seen until 8 weeks post injection. Our results also showed a unique pattern of distribution of the transgene and the vector. Transgene activity was localized in the spinal cord, brainstem, and midbrain whereas the mRNA expression of the virus/vector was confined predominantly to the cerebral cortex. In addition to analyzing the transgene pattern at the mRNA level we also quantitate the amount of GUSB activity. Our results showed that there was a significant increase in the amount of protein produced in the different parts of the brain in the animals injected with BB2 compared with control HSV-1 virus. In addition to the intrathecal route two other peripheral routes of inoculation were tried, intraocular and intranasal. Neither of these routes showed any expression of the transgene or the protein. One possible reason for the failure of expression by these two routes is because 1716 virus cannot effectively spread/establish latency in the CNS when inoculated peripherally. In conclusion we have developed a comparatively noninvasive mode of delivery of recombinant virus into the CNS which could eventually be used for correction of CNS pathology in MPS vii mice.
709. Gene Correction and Gene Knockouts in Human Somatic Cells Using Zinc Finger Nucleases
Authors: Matthew H. Porteus
Journal: Molecular Therapy (2004)

A potentially ideal way to treat monogenic diseases is to correct the mutation that causes the disease rather than complement the mutation by adding back an unmutated copy of the gene. One way of performing gene correction is by gene targeting. Gene targeting is the replacement of an endogenous segment of DNA with a homologous exogenous segment of DNA by homologous recombination. The rate of gene targeting is usually far too low in human somatic cells to be of therapeutic or experimental utility. If a DNA double-strand break is created in the genomic target gene, however, the rate of gene targeting increases by several thousand fold and can reach an overall rate of 3-5%. These high rates of gene targeting were achieved using the I-SceI endonuclease (Sce) and by inserting a Sce target site into a reporter gene. For gene targeting to become useful, a method to create a DSB in any target gene, without the prior insertion of a Sce target site, needs to be developed. Towards this end we have found that model zinc finger nucleases, artificial protein fusions between a zinc finger DNA binding domain and a the endonuclease domain from the FokI restriction enzyme, could stimulate gene targeting nearly as efficiently as Sce in human somatic cells. Zinc finger nucleases act as dimers in which two binding sites (“ZFN half-sites”) are in an inverted orientation separated by six basepairs (“ZFN full site”). In this work, I show that zinc finger nucleases can be designed to stimulate gene targeting at half sites from the human-β globin and the human common-γ chain genes. These half-sites had the consensus sequence 5′-GNNGNNGNN-3′. Furthermore, I was able to design zinc finger nucleases to stimulate gene targeting at the “ZFN full-site consensus sequence” 5′-nnCnnCnnC833nGnnGnnGnn-3′. The GFP gene contains a natural ZFN full site consensus sequence and the GFP zinc finger nucleases stimulated gene correction by gene targeting by 1000-fold at this site. The human CD8α gene also contains a ZFN full site consensus sequence and the CD8 zinc finger nucleases efficiently stimulated gene knockouts via gene targeting in human somatic cells. Overall, therefore, zinc finger nucleases to stimulate gene targeting in endogenous genes can be generated by to the ZFN full site consensus sequence using a relatively easy “off-the-shelf” approach. This finding raises the possibility of being able to use gene targeting as an experimental tool in human somatic cell genetics and, with further development, the possibility of treating monogenic diseases via gene targeting and zinc finger nucleases.