tbuckley/cabot-search huggingface dataset:
Application of magnetic resonance imaging in transgenic and chemical mouse models of hepatocellular carcinoma
Authors: Julia Freimuth, Nikolaus Gassler, Nives Moro, Rolf W. Günther, Christian Trautwein, Christian Liedtke, Gabriele A. Krombach
Journal: Molecular Cancer (2010)

Abstract Background Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. The molecular mechanisms underlying hepatocarcinogenesis are still poorly understood. Genetically modified mice are powerful tools to further investigate the mechanisms of HCC development. However, this approach is limited due to the lack of non-invasive detection methods in small rodents. The aim of this study was to establish a protocol for the non-invasive analysis of hepatocarcinogenesis in transgenic mice using a clinical 1.5 Tesla Magnetic Resonance Imaging scanner. Results As a model system we used hepatocyte-specific c-myc transgenic mice developing hepatocellular carcinoma at the age of 12-15 months. The scans of the murine livers included axial T2-weighted turbo-spin echo (TSE) images, axial T1-weighted and contrast enhanced T1-weighted gradient echo (fast field echo, FFE) and sagittal true Fast Imaging with Steady state Precession (true-FISP) images. Application of contrast agent was performed via tail vein-catheter and confirmed by evaluation of the altered longitudinal relaxation T1 time before and after application. Through technical adaptation and optimization we could detect murine liver lesions with a minimum diameter of approximately 2 mm and provided histopathological evidence that these MR findings correspond to hepatocellular carcinoma. Tumor growth was repeatedly measured using sequential MRI with intervals of 5 weeks and subsequent volumetric analysis facilitating direct comparison of tumor progression between individual animals. We finally demonstrated that our protocol is also applicable in the widely- used chemical model of N-nitrosodiethylamine-induced hepatocarcinogenesis. Conclusion Our protocol allows the non-invasive, early detection of HCC and the subsequent continuous monitoring of liver tumorgenesis in transgenic mice thereby facilitating future investigations of transgenic tumor mouse models of the liver.
Ciprofloxacin plus piperacillin is an equally effective regimen for empiric therapy in febrile neutropenic patients compared with standard therapy
Authors: Jennifer J. Griggs, E. Allen Blair, J. Russel Norton, Jacob M. Rowe, William R. Flesher, Robert F. Betts
Journal: American Journal of Hematology (1998)

The purpose of this study was to test the comparative efficacy and toxicity of empiric gentamicin and ciprofloxacin, in combination with piperacillin, in febrile patients with treatment-induced neutropenia. Fifty patients were prospectively randomized to receive piperacillin plus gentamicin (PG), and 46 were randomized to receive piperacillin plus ciprofloxacin (PC). The groups were similar in age, sex, diagnosis, duration of neutropenia, and incidence of positive cultures. The two antibiotic regimens were associated with comparable rates of defervescence in the patients with Gram-positive bacteremia. In the patients with Gram-negative bacteremia and those with negative cultures, however, defervescence was more prompt in the PC group. In particular, 27% of the culture-negative patients on PC, compared to only 5% of those on PG, defervesced within 72 hr (P = 0.015). Because of the more prompt defervescence in the PC group, amphotericin B was used less frequently; 78% of the patients on PG compared with only 56% of those on PC were started on amphotericin B (P J Biomed Mater Res, 41, = 0.025). PC is an effective alternative to the more traditional PG for treatment of febrile neutropenic hosts who have not been given prophylactic quinolones. More important, PC appears to hasten defervescence compared with PG, especially in culture-negative patients and those with Gram-negative bacteremia, and may decrease the necessity of additional antimicrobial agents such as amphotericin B. 1998. Am. J. Hematol. 58: 293–297, 1998. © 1998 Wiley-Liss, Inc.
Simulation of Action Potentials From Metabolically Impaired Cardiac Myocytes
Authors: José M. Ferrero, Javier Sáiz, José M. Ferrero, Nitish V. Thakor
Journal: Circulation Research (1996)

The role of the ATP-sensitive K + current (I K-ATP ) and its contribution to electrophysiological changes that occur during metabolic impairment in cardiac ventricular myocytes is still being discussed. The aim of this work was to quantitatively study this issue by using computer modeling. A model of I K-ATP is formulated and incorporated into the Luo-Rudy ionic model of the ventricular action potential. Action potentials under different degrees of activation of I K-ATP are simulated. Our results show that in normal ionic concentrations, only ≈0.6% of the K ATP channels, when open, should account for a 50% reduction in action potential duration. However, increased levels of intracellular Mg 2+ counteract this shortening. Under conditions of high [K + ] o , such as those found in early ischemia, the activation of only ≈0.4% of the K ATP channels could account for a 50% reduction in action potential duration. Thus, our results suggest that opening of I K-ATP channels should play a significant role in action potential shortening during hypoxic/ischemic episodes, with the fraction of open channels involved being very low (&lt;1%). However, the results of the model suggest that activation of I K-ATP alone does not quantitatively account for the observed K + efflux in metabolically impaired cardiac myocytes. Mechanisms other than K ATP channel activation should be responsible for a significant part of the K + efflux measured in hypoxic/ischemic situations.
Role of Anti-Hepatitis C Virus (HCV) Treatment in HCV-Related, Low-Grade, B-Cell, Non-Hodgkin's Lymphoma: A Multicenter Italian Experience
Authors: Daniele Vallisa, Patrizia Bernuzzi, Luca Arcaini, Stefano Sacchi, Vittorio Callea, Roberto Marasca, Antonio Lazzaro, Elena Trabacchi, Elisa Anselmi, Anna Lisa Arcari, Carlo Moroni, Raffaella Bertè, Mario Lazzarino, Luigi Cavanna
Journal: Journal of Clinical Oncology (2005)

Hepatitis C virus (HCV) is endemic in some areas of Northwestern Europe and the United States. HCV has been shown to play a role in the development of both hepatocellular carcinoma and B-cell non-Hodgkin's lymphoma (B-NHL). The biologic mechanisms underlying the lymphomagenic activity of the virus so far are under investigation. In this study, the role of antiviral (anti-HCV) treatment in B-NHL associated with HCV infection is evaluated.Thirteen patients with histologically proven low-grade B-NHL characterized by an indolent course (ie, doubling time no less than 1 year, no bulky disease) and carrying HCV infection were enrolled on the study. All patients underwent antiviral treatment alone with pegilated interferon and ribavirin. Response assessment took place at 6 and 12 months.Of the twelve assessable patients, seven (58%) achieved complete response and two (16%) partial hematologic response at 14.1 +/- 9.7 months (range, 2 to 24 months, median follow-up, 14 months), while two had stable disease with only one patient experiencing progression of disease. Hematologic responses (complete and partial, 75%) were highly significantly associated to clearance or decrease in serum HCV viral load following treatment (P = .005). Virologic response was more likely to be seen in HCV genotype 2 (P = .035), while hematologic response did not correlate with the viral genotype. Treatment-related toxicity did not cause discontinuation of therapy in all but two patients, one of whom, however, achieved complete response.This experience strongly provides a role for antiviral treatment in patients affected by HCV-related, low-grade, B-cell NHL.
William Mortimer Haigh Shaw
Authors: M. Shaw
Journal: BMJ (2002)

Professor of medicine whose famous report on inequality and health fell foul of the Thatcher government Sir Douglas Black was one of medicine's most important and well loved individuals.His many achievements included a professorship of medicine in Manchester, research on salt and water balance, persuading the profession in the 1940s and 1950s that the NHS was a good thing, and the presidency of the Royal College of Physicians.But he is best known for his 1980 Black report, which spelt out the social inequalities in health and proposed ways of reducing them.In 1977 the then Labour government's health secretary, David Ennals, chaired an expert committee investigating why the NHS had apparently failed to reduce social inequalities in health, and he commissioned Black to write a report.The result was published-or, rather, suppressed-in 1980, when the Conservatives had come to power.The Black report was not to Mrs Thatcher's liking and was never printed; instead, 260 photocopies were distributed in a half hearted fashion on Bank Holiday Monday.However, the report had a huge impact on political thought in the United Kingdom and overseas.It led to an assessment by the Office for Economic Co-Operation and Development and the World Health Organization of health inequalities in 13 countries-though not on UK government policy.Penguin Books later published a shorter version of the report.Black provided convincing figures that showed what many suspected-that the poorest had the highest rates of ill health and death.He argued that these rates could not be explained solely by income, education, mobility, or lifestyle, but were also caused by a lack of a coordinated policy that would ensure uniform delivery of services.He recommended health goals, tax changes, benefit increases, and restrictions on the sale and advertising of tobacco.Patrick Jenkin, the social services secretary, estimated with a shudder that Black's proposals-which he hinted were little short of outrageouswould cost an unthinkable £2bn a year.Thin, gentle mannered, poker faced, and self effacing, Black was deeply moral, always serious, and frequently extremely funny.His after dinner speeches were received with rapt attention, as to miss a moment of that soft Scottish voice was to miss a joke.He
Lenalidomide Inhibits Lymphangiogenesis in Preclinical Models of Mantle Cell Lymphoma
Authors: Kai Song, Brett H. Herzog, Minjia Sheng, Jianxin Fu, J. Michael McDaniel, Jia Ruan, Lijun Xia
Journal: Cancer Research (2013)

Lymphomas originate in and spread primarily along the lymphatic system. However, whether lymphatic vessels contribute to the growth and spreading of lymphomas is largely unclear. Mantle cell lymphoma (MCL) represents an aggressive non-Hodgkin's lymphoma. We found that MCL exhibited abundant intratumor lymphatic vessels. Our results demonstrated that the immunomodulatory drug lenalidomide potently inhibited the growth and dissemination of MCL in a xenograft MCL mouse model, at least in part, by inhibiting functional tumor lymphangiogenesis. Significant numbers of tumor-associated macrophages expressing vascular endothelial growth factor-C were found in both human MCL and mouse MCL xenograft samples. Lenalidomide treatment resulted in a significant reduction in the number of MCL-associated macrophages. In addition, in vivo depletion of monocytes/macrophages impaired functional tumor lymphangiogenesis and inhibited MCL growth and dissemination. Taken together, our results indicate that tumor lymphangiogenesis contributes to the progression of MCL and that lenalidomide is effective in decreasing MCL growth and metastasis most likely by inhibiting recruitment of MCL-associated macrophages.
Cutaneous leishmaniasis responds to daylight-activated photodynamic therapy: proof of concept for a novel self-administered therapeutic modality
Authors: C.D. Enk, A. Nasereddin, R. Alper, M. Dan-Goor, C.L. Jaffe, H.C. Wulf
Journal: British Journal of Dermatology (2014)

Cutaneous leishmaniasis (CL) is endemic in Israel, with hundreds of new cases reported in recent years. Photodynamic therapy (PDT) is highly effective for treatment of CL, but requires equipment available only at specialized centres. Daylight-activated PDT (DA-PDT) abolishes the need for artificial light sources and allows the patient to administer the treatment with no professional assistance.The objective of this single-centre, open study was to establish proof of concept for the efficacy of DA-PDT in the treatment of CL using clinical, microbiological and molecular clearance as outcome measures.Thirty-one patients with CL (11 Leishmania major and 20 Leishmania tropica) underwent DA-PDT. Fourteen patients were treated in the hospital garden under professional supervision and 17 patients underwent DA-PDT as a self-administered treatment modality at home. Following application of a thick layer of 16% methyl aminolaevulinate and 30-min occlusion, the lesions were exposed to daylight for 2·5 h. Treatment sessions were repeated at weekly intervals until clinical and microbiological cure. Control lesions were either treated with cryotherapy or left untreated.The overall cure rate for DA-PDT was 89% (intention-to-treat cure rate 77%); this was 86% for the hospital-based treatment group and 92% for the self-administered group.DA-PDT proved to be effective in the treatment of CL caused by L. major and L. tropica. More patients were treated according to a self-administered protocol, suggesting that DA-PDT can be adopted even in technologically deprived countries where the majority of Leishmania infections are encountered.
Role for Brm in Cell Growth Control
Authors: Marjorie Coisy-Quivy, Olivier Disson, Virginie Roure, Christian Muchardt, Jean-Marie Blanchard, Jean-Christophe Dantonel
Journal: Cancer Research (2006)

Abstract Recently, we have shown implication of Brm, the catalytic subunit of the SWI/SNF chromatin remodeling complex, in repression of cyclin A expression in quiescent cells. Here, we have examined the fate of cells lacking Brm throughout the cycle. We find that despite elevated levels of cyclins A and E, these cells can respond to serum starvation, however, without reaching a canonical G0 phase as they continue to express high levels of c-Myc and have an abnormally large average size. The response to serum starvation can be correlated with increased levels of Rb proteins p130 and p107 as well as increased association of p27 with the cyclin-dependent kinases, possibly compensating for the higher levels of G1 cyclins by reducing their associated kinase activity. After serum stimulation, reentry into the cycle occurs normally, but the S phase is delayed and shorter. In addition, the M phase has an increased duration, and we observed frequent faulty chromosome segregation events in anaphase. Altogether, our data suggest that cells can partially overcome the absence of Brm by activating several compensatory mechanisms to control the cell cycle. However, they remain profoundly affected, unable to enter a canonical quiescent state, presenting a shorter S phase, and finally unable to perform correct chromosome segregation. (Cancer Res 2006; 66(10): 5069-76)
Expression of the phenotypic abnormality of platelet-type von Willebrand disease in a recombinant glycoprotein Ib alpha fragment.
Authors: M Murata, S R Russell, Z M Ruggeri, J Ware
Journal: Journal of Clinical Investigation (1993)

The platelet GP Ib-IX receptor supports platelet adhesion and activation by binding to vWf in the exposed subendothelial matrix. An abnormal GP Ib-IX complex exists in platelet-type or pseudo-von Willebrand disease and has a characteristic increased affinity for soluble vWf resulting in impaired hemostatic function due to the removal of larger vWf multimers from the circulation. Genetic studies within an afflicted family have demonstrated that the disease is linked to a Gly233-->Val amino acid substitution within the alpha-subunit of the oligomeric GP Ib-IX complex (Miller, J.L., D. Cunningham, V.A. Lyle, and C. L. Finch. 1991. Proc. Natl. Acad. Sci. USA. 88:4761-4765). To evaluate the functional consequences of this mutation, we constructed a recombinant analogue of the alpha-subunit of GP Ib containing Val233. Experiments comparing molecules with either Gly233 or Val233 revealed that the Val substitution generates a molecule with increased affinity for vWf. The recombinant fragment reproduces the functional abnormality of the GP Ib-IX complex in platelet-type von Willebrand disease, thus establishing the molecular basis of the bleeding disorder within this family. Moreover, it becomes apparent that structural elements responsible for the regulation of hemostasis through modulation of vWf affinity for platelets reside within the alpha-subunit of the GP Ib-IX complex.
The Evolving Treatment of Aortic Stenosis
Authors: John D. Carroll
Journal: Circulation (2006)

he percutaneous treatment of valvular heart disease is rapidly progressing through clinical trials.For one valvular lesion, critical aortic stenosis, recent advances in technology and percutaneous techniques may potentially change the way in which we manage this disease in the most frail and elderly patients.Some of these new techniques blur the distinction between surgical and nonsurgical treatments.In this issue of Circulation, Lichtenstein and colleagues report the first series of patients to have an aortic valve implanted via a thoracotomy to expose the left ventricular apex, for subsequent sheath insertion, over-the-wire delivery system advancement, and image-guided implantation of a stent mounted equine crimped on a delivery balloon. 1 This article is seminal in defining 2 major emerging issues: valvular heart disease treatments that are hybrids of surgical and catheter-based techniques and the challenges inherent in determining what treatment modalities are best in the growing problem of aortic stenosis in mature, ie, elderly, adults.This report adds to the recently published report from the St. Paul's Hospital group in Vancouver using the retrograde percutaneous aortic valve (PAV) implantation technique. 2 Article p 591Which patients will be appropriate for these new approaches to the treatment of aortic stenosis in the mature adult population?Timely assessment of the efficacy and safety of these techniques will be critical for patients, care providers, regulatory agencies, and insurers to evaluate for patientspecific decision making and healthcare policy.
Ionic Remodeling of Sinoatrial Node Cells by Heart Failure
Authors: Arie O. Verkerk, Ronald Wilders, Ruben Coronel, Jan H. Ravesloot, E. Etienne Verheijck
Journal: Circulation (2003)

In animal models of heart failure (HF), heart rate decreases as the result of an increase in intrinsic cycle length of the sinoatrial node (SAN). In this study, we evaluate the HF-induced remodeling of membrane potentials and currents in SAN cells.SAN cells were isolated from control rabbits and rabbits with volume and pressure overload-induced HF and patch-clamped to measure their electrophysiological properties. HF cells were not hypertrophied (capacitance, mean+/-SEM, 52+/-3 versus 50+/-4 pF in control). HF increased intrinsic cycle length by 15% and decreased diastolic depolarization rate by 30%, whereas other action potential parameters were unaltered. In HF, the hyperpolarization-activated "pacemaker" current (If) and slow component of the delayed rectifier current (IKs) were reduced by 40% and 20%, respectively, without changes in voltage dependence or kinetics. T-type and L-type calcium current, rapid and ultrarapid delayed rectifier current, transient outward currents, and sodium-calcium exchange current were unaltered.In single SAN cells of rabbits with HF, intrinsic cycle length is increased as the result of a decreased diastolic depolarization rate rather than a change in action potential duration. HF reduced both If and IKs density. Since IKs plays a limited role in pacemaker activity, the HF-induced decrease in heart rate is attributable to remodeling of If.
A randomized trial of consensus interferon in combination with ribavirin as initial treatment for chronic hepatitis C
Authors: Giovanna Fattovich, Irene Zagni, Eliseo Minola, Martina Felder, Pierangelo Rovere, Antonio Carlotto, Sergio Suppressa, Anna Miracolo, Claudio Paternoster, Caterina Rizzo, Angelo Rossini, Paolo Benedetti, Marco Capanni, Chiara Ferrara, Paolo Costa, Tosca Bertin, Maurizio Pantalena, Lorenzo Lomonaco, Chiara Scattolini, Giuseppe Mazzella, Massimo Giusti, Sergio Boccia, Stefano Milani, Renato Marin, Maria Lisa Ribero, Alessandro Tagger
Journal: Journal of Hepatology (2003)
Return to Work after Uncomplicated Myocardial Infarction: A Trial of Practice Guidelines in the Community
Authors: L Pilote, R J Thomas, C Dennis, P Goins, N Houston-Miller, H Kraemer, C Leong, W E Berger, H Lew, R S Heller
Journal: Annals of Internal Medicine (1992)

▪ Objective: To evaluate the effectiveness of practice guidelines for return to work after acute myocardial infarction when disseminated from a university-based setting to a practice-based setting. ▪ Design: Randomized clinical trial. ▪ Patients: A total of 187 patients with uncomplicated acute myocardial infarction. ▪ Intervention: Patients were randomly assigned to the intervention (n = 95) or to usual care (n = 92). The intervention consisted of a treadmill test, a counseling session based on the test results, and a consultation letter from a cardiologist to the primary care physician. Individualized recommendations for the timing of return to work, contained in the consultation letter, were based on the patient's risk for recurrent cardiac events. ▪ Measurements: Questionnaire, chart review, and a phone interview documented the timing of return to work and the rates of cardiac death, coronary angioplasty, coronary artery surgery, and recurrent myocardial infarction. ▪ Results: Median intervals between acute myocardial infarction and return to work were similar in both groups (intervention, 54 days; usual care, 67 days; P > 0. 2). Among patients without myocardial ischemia, however, the interval was shorter in the intervention group than in the usual care group (38 days compared with 65 days, respectively, P = 0.008). Among patients with myocardial ischemia, intervals were similar in both groups (80 days compared with 76 days, respectively, P > 0.2). ▪ Conclusion: Practice guidelines developed in a university-based setting were not as successful in hastening return to work after uncomplicated acute myocardial infarction when tested in a practice-based setting. Physicians' reluctance to follow guidelines for patients with myocardial ischemia reflected their concern with prognosis even though medical outcome was good.