tbuckley/cabot-search huggingface dataset:
Implementation of clinical trials in unselected non-small cell lung cancer (NSCLC) patients: The mitomycin, ifosfamide, cisplatin (MIP) regimen
Authors: T. Berghmans, A.-P. Meert, V. Ninane, J.-P. Sculier
Journal: Journal of Clinical Oncology (2005)

7287 Background:There are with clinical trials problems of external validity due to patients’ selection. Applicability to general population has to be demonstrated. For example, the European Union in proposing the AGREE instrument to assess published guidelines asks for complementary validation of guidelines in unselected target population. Implementation studies allow to evaluate the efficacy of treatment in routine practice. We performed a methodological study to implement the MIP chemotherapy in a general population, comparing the results to those obtained in clinical trials. Patients and Methods: Between 1987 and 2004, 204 patients with NSCLC received MIP in our institution. Patients treated in and off trials received the same combination of cisplatin (50 mg/m2), ifosfamide (3 g/m2) and mitomycin C (6 mg/m2) every 3 weeks and were staged and followed similarly. Results: There were 78 patients (38.2%) treated inside protocols. Response rates and median survival times were for patients treated in or off trials 36.8% and 40.7% (p=0.59) and 54.6 and 43.7 weeks (p=0.06), respectively. In multivariate analysis, 4 factors were significantly associated with better survival: good PS (p = 0.003), normal LDH value (p < 0.001), early stage (p = 0.01) and active smoking (p = 0.03). Conclusion: With this implementation study, we confirm in unselected patients with NSCLC, the activity of MIP as reported in clinical trials. Participation to a clinical trial was not associated with a better outcome. No significant financial relationships to disclose.
546. Optimization of Expression of the SIV-Specific 9456 Ribozyme by the tRNAval PolIII Promoter within an MLV- or Lentiviral-Vector
Authors: Joshua N. Leonard, David V. Schaffer
Journal: Molecular Therapy (2004)

Top of pageAbstract
RNA interference (RNAi) is an innate cellular process in which double-stranded small interfering RNAs (siRNAs) act as triggers to induce sequence-specific degradation of RNA molecules with which they share homology. RNAi has been shown to effectively reduce the expression of viral genes in vitro, which suggests that it might be especially useful as a genetic therapy to combat or protect against viral pathogens that have RNA genomes, such as human immunodeficiency virus (HIV). However, the RNAi response is so specific that several nucleotides of non-homology between the siRNA and the viral RNA are sufficient to significantly impede target degradation. Since HIV mutates rapidly, the emergence of resistant strains is a major obstacle to potential clinical applications. Using an integrated computational and experimental approach, we are studying HIV evolution in response to RNAi pressure in order to develop quantitative design strategies that delay or prevent viral escape. We constructed a novel stochastic simulation that mechanistically models HIV replication, and we used such simulations to make some counterintuitive predictions about the efficacies of several antiviral RNAi strategies. Design considerations we have investigated computationally include the number of HIV sequences targeted, the uniformity of siRNA delivery, and the consequences of targeting the tat-TAR feedback loop. To test these hypotheses experimentally, we developed a lentiviral siRNA vector that induces sustained and dose-dependent reductions (up to >95%) of target gene expression. With this vector, we can effectively and specifically target highly conserved regions of the HIV genome for RNAi-mediated degradation. This system was used to create stable cell lines that can now serve as tunable RNAi challenges for a replicating HIV model virus. We anticipate that these studies will be useful for identifying antiviral RNAi therapy strategies that most effectively suppress HIV infections.
Activation of aryl hydrocarbon receptor dissociates fatty liver from insulin resistance by inducing fibroblast growth factor 21
Authors: Peipei Lu, Jiong Yan, Ke Liu, Wojciech G. Garbacz, Pengcheng Wang, Meishu Xu, Xiaochao Ma, Wen Xie
Journal: Hepatology (2015)

The aryl hydrocarbon receptor (AHR), also known as the dioxin receptor, was originally characterized as a xenobiotic receptor that senses xenotoxicants. We investigated the endobiotic and hepatic role of AHR in fatty liver and energy metabolism and identified the endocrine factor that mediates the metabolic function of AHR. Wild-type and liver-specific constitutively activated human AHR transgenic mice were used to investigate the role of AHR in fatty liver and energy homeostasis. Adenovirus expressing short hairpin RNA targeting fibroblast growth factor 21 (FGF21) were used to determine the involvement of FGF21 in the metabolic effect of AHR. We showed that, despite their severe fatty liver, the transgenic mice were protected from diet-induced obesity and type 2 diabetes. We identified the endocrine hormone FGF21 as a mediator for the metabolic benefit of AHR and established FGF21 as a direct transcriptional target of AHR. Interestingly, the transactivation of FGF21 by AHR contributed to both hepatic steatosis and systemic insulin hypersensitivity, both of which were largely abolished upon FGF21 knockdown.The AHR-FGF21 endocrine signaling pathway establishes AHR as a pivotal environmental modifier that integrates signals from chemical exposure in the regulation of lipid and energy metabolism.
Peak Mitral Inflow Velocity Predicts Mitral Regurgitation Severity 11All editorial decisions for this article, including selection of referees, were made by a Guest Editor. This policy applies to all articles with authors from the University of California San Francisco.22To discuss this article on-line, visit the ACC Home Page at www.acc.org/membersand click on the JACC Forum
Authors: Liza Thomas, Elyse Foster, Nelson B. Schiller
Journal: Journal of the American College of Cardiology (1998)
Promise of Immune Modulation to Inhibit Atherogenesis⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Christoph J. Binder, Karsten Hartvigsen, Joseph L. Witztum
Journal: Journal of the American College of Cardiology (2007)
Risk of Death With Nesiritide—Reply
Authors: Jonathan D. Sackner-Bernstein, Keith Aaronson
Journal: JAMA (2005)

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
An unusual case of plastic bronchitis
Authors: Francesca Petreschi, Teresa Salerno, Maria Beatrice Chiarini Testa, Maria Giovanna Paglietti, Alessandra Schiavino, Laura Menchini, Sergio Bottero, Alessandro Inserra, Renato Cutrera
Journal: European Respiratory Journal (2013)

RF, 10 years old girl was first observed when she was 9 years and 8 months old, for suspected plastic bronchitis, after the release of a cast during an acute episode of asthma.

Clinical history was uneventful up to 2009, when she suffered from an acute pneumonia. From September 2011 she presented recurrent bronchial asthma.

In march 2012 she had a persistent bronchospasm with progressive worsening of general conditions and expectoration of a cast; she underwent Bronchoscopy, Chest CT, angioMRI, lymphoscintigraphy that showed a lymphobronchial fistula with dysplasia of lymphatic return and stasis in the lung. Bronchoalveolar lavage and aspiration liquid chemical analysis showed a high amount of tryglicerides and no-esterified fatty acids. A low fat diet with integration of MCT oil was started with initial clinical improvement. After one month she presented again respiratory symptoms worsening and chiloptisi.

Chest X ray demonstrated a wide interstitial lung disease.

A plasminogen activator (altoplase) inhaled treatment was started, with subsequent clinical improvement.

In October 2012 she had a new clinical worsening, she underwent a total parenteral nutrition.

In order to differentiate a primary from a secondary pulmonary lymphangectasis, we performed a lung biopsy that proved to be consistent with a secondary form.

She underwent ligation of the thoracic duct, to exclude the portion of the abdominal lymph tributary lung.

After two weeks she was discharged without pharmacological treatment and cholesterol-free diet.

After 40 days from discharge we have witnessed a partial recovery of lung function with normal daily activities recovery and after three months an almost complete recovery of lung function.
Abstract 4696: Different Outcome in Shock Patients Treated by Multivessel Versus Target-Vessel Only PCI for STEMI and Resuscitated Cardiac Arrest
Authors: Philippe Garot, Thierry Lefevre, Helene Eltchaninoff, Jerome Garot, Claude Pouges, Jean-Yves Le Tarnec, Alain Margenet, Dominique Thebert, Jean-Francois Angellier, Yves Louvard, Marie-Claude Morice
Journal: Circulation (2009)
Purified Photoproducts of Merocyanine 540 Trigger Cytochrome C Release and Caspase 8-Dependent Apoptosis in Human Leukemia and Melanoma Cells
Authors: Shazib Pervaiz, Mohamed A. Seyed, Jayshreekumari L. Hirpara, Marie-Véronique Clément, Kok W. Loh
Journal: Blood (1999)
Abstract 9770: Plasma Biomarkers for Response to Transforming Growth Factor-Beta Antagonism After Acute Myocardial Infarction
Authors: Peter C Yaeger, Jeffrey D Stewart, Issam Ayoub, Zhiqiang Jia, Jia Zhiqiang, Xiaohong Cao, Srinivas Shankara, Amelia B Kudej, Geoffrey Y Akita
Journal: Circulation (2014)

Transforming Growth Factor-Beta (TGF-β) induces a fibrotic response to tissue injury and contributes to pathological cardiac remodeling during the weeks following myocardial infarction. We are investigating the potential utility of circulating microRNA (miRNA) as biomarkers for therapeutic response to treatment of myocardial infarction with a neutralizing antibody against TGF-β. In a rat model of cardiac ischemia- reperfusion (IR), 1D11, an antibody which neutralizes TGF-β1, 2 and 3, was injected intravenously at a dose of 0, 1, or 5 mg/kg (IR-0, IR-1, and IR-5) every 3 days starting 3 to 5 days after IR. Sham surgery controls did not undergo ischemia or 1D11 treatment. Plasma was collected for miRNA isolation three weeks after IR or sham surgery. The HTG Molecular platform, which is based on nuclease protection, was used to compare Sham, IR-0, and IR-5 groups (n=5 rats per group) for the relative abundance of approximately 1000 unique miRNAs. MiRNA was normalized to plasma volume. Based on the modulation of their plasma levels by IR and 1D11 treatment, 41 miRNAs were selected for further testing. A focused array was designed to interrogate plasma samples from 2 independent rat studies performed as described above. Study 1 compared 3 groups: Sham, IR-0 and IR-1 (N=6 rats/group). Study 2 compared Sham (N=5), IR-0 (N=10), and IR-5 (N=12), In both studies, at 3 weeks post IR plasma levels of 13 miRNAs (miRs 17, 106a, 21, 23a, 27a, 27b, 103a, 128, 142-5p, 181a, 223, 425, 652) were significantly (p
Abstract 15563: Neurovascular Control and Spontaneous Baroreflex Sensitivity in Heart Failure Patients with Preserved Ejection Fraction
Authors: Ana Luiza C Sayegh, Marcelo R dos Santos, Francis R de Souza, Vera Maria C Salemi, Carlos Augusto P Oliveira, Felipe X Fonseca, Sara Rodrigues, Ivani C Trombetta, Edgar Toschi-Dias, Carlos Eduardo Negrão, Maria-Janieire N Alves, Charles Mady
Journal: Circulation (2014)

Introduction: Muscle sympathetic nerve activity (MSNA) and forearm blood flow (FBF) are markers of mortality in Systolic Heart Failure (S-HF). Endomyocardial Fibrosis (EMF) is a Heart Failure (HF) with Preserved Ejection Fraction (PEF-HF). Although mortality in PEF-HF can be similar to S-HF, it is still unknown if neurovascular control is impaired in PEF-HF. Hypothesis: Our hypothesis is that even though PEF-HF show normal ejection fraction, they have the same autonomic dysfunction as S-HF. The aim was to evaluate MSNA, FBF and spontaneous baroreflex sensitivity (SBS) in PEF-HF compared to S-HF and healthy subjects (HS). Methods: Nineteen females HF, NYHA class II and III, were divided in two groups: PEF-HF (n=10) and S-HF (n=9), and were compared to HS (n=7). Left Ventricular Ejection Fraction (LVEF), by echocardiography (Simpson); MSNA, by microneurography; FBF, by venous occlusion plethysmography; mean blood pressure (MBP) and heart rate (HR) by Finometer; SBS, by sequence method, were measured. Significance was considered p&lt;0.05. Results: Age was not different between PEF-HF, S-HF and HS (57±2 vs. 55±2 vs. 52±1 years; p&lt;0.15, respectively). LVEF was higher in PEF-HF and HS compared to S-HF (55±3 vs. 65±1 vs. 33±2%; p&lt;0.02, respectively). MSNA in bursts per minute (35±3 vs. 40±2 vs. 20±1 bursts/min; p&lt;0.001) and MSNA per 100 heart beats (50±4 vs. 57±3 vs. 26±2 bursts/100 HB; p&lt;0.001) were higher in PEF-HF and S-HF compared to HS, respectively. FBF was lower in PEF-HF and S-HF compared to HS (1.45±0.2 vs. 1.78±0.3 vs. 2.70±0.3 ml/min/100ml; p&lt;0.047). Forearm vascular conductance was lower in PEF-HF compared to HS (1.63±0.2 vs. 2.98±0.3 units; p&lt;0.008) but PEF-HF was not different compared to S-HF (1.63±0.2 vs. 2.04±0.3 units; p&lt;0.28). MBP (92±3 vs. 89±4 vs. 92±4 mmHg; p=0.87) and HR (71±3 to 70±3 vs. 75±3 beats/min; p&lt;0.46) were not different between groups. However, SBS was not different between PEF-HF and S-HF (2.3±0.5 vs. 6.9±4.4 ms/mmHg; p=0.089, respectively) but PEF-HF was lower when compared to HS (2.3±0.5 vs. 8.1±0.7 ms/mmHg; p=0.047, respectively). Conclusion: These results point out that even though PEF-HF have a normal ejection fraction, they showed neurovascular control as impaired as S-HF with lower SBS compared to HS.
Prognosis of symptoms that are medically unexplained
Authors: M. Gotz, A. House
Journal: BMJ (1998)

Prognosis of symptoms that are medically unexplained Every neurology service should have access to specialist liaison psychiatryEditor-Crimlisk et al's report on the outcome of motor symptoms that were medically unexplained in a cohort first identified at the National Hospital for Nervous Diseases is welcomed by those interested in the psychiatry of physical illness. 1 Slater's work, based on cohorts recruited in the 1950s, overestimated the likelihood of misdiagnosis in modern neurology, 2 and his conclusions have dissuaded psychiatrists from becoming involved in the management of hysteria.O'Brien's editorial on Crimlisk et al's study could have sounded two cautionary notes. 3Firstly, the study was not based on a true inception cohort, and it was recruited from a highly specialised centre.Usually, these factors lead to the finding of a worse prognosis than if only incident cases were included and the sample was less prone to recruitment bias.In this case, however, the bias may have been in the other direction.Patients seen at the National Hospital are likely to have been more exhaustively investigated and observed for longer (either in this episode or before referral) than they would be in most hospitals, so that the chances of misdiagnosis are reduced.We should not generalise the study findings to hospitals where initial assessment may be undertaken with little or no access to specialist neurological opinion or investigations.Secondly, the negative message-that high rates of undetected neurological disease are not seen at follow up-has been allowed to obscure the important positive findings of the study.Even years later, the patients had disabling physical symptoms and substantial psychiatric problems.As in Slater's original study, preventable deaths occurred from suicide and the complications of immobility.Many people were apparently not referred for psychiatric help either at the time of the initial presentation or subsequently.The important conclusion of Crimlisk et al's study must be that every neurology service should have easy access to referral to specialist liaison psychiatry. 4This group of patients, who are difficult to treat, are often resistant to treatment, and have a poor prognosis, may then have a reasonable chance of obtaining appropriate treatment for their primary disorder.
Abstract 788: Lichen-derived metabolites show synergistic effects in combination with lapatinib and doxorubicin against breast cancer cells
Authors: Margret Bessadottir, Edda A. Skuladottir, Sindri Baldursson, Sesselja Omarsdottir, Helga M. Ögmundsdottir
Journal: Cancer Research (2014)

Abstract Protolichesterinic acid (PA) is the major biologically active second metabolite of the lichen Cetraria islandica. PA has anti-proliferative effects on several types of cancer cells, but no effect on normal skin fibroblasts and is an inhibitor of 5- and 12-lipoxygenase (LOX). Usnic acid (UA) (from Cladonia arbuscula) has a wide range of biological activities, e.g. anti-inflammatory, anti-viral and anti-bacterial activity. UA affects pH gradients and inhibits growth and proliferation of several cancer cells. Fatty acid synthase (FASN) is up-regulated in a variety of cancers. Overexpression of human epidermal growth factor receptor 2 (HER2) has been linked to increased translation of FASN. The chemical structure of PA is very similar to the FASN inhibitor, C75. FASN inhibition interacts synergistically with HER2 targeted drugs (e.g. lapatinib) in breast cancer cells and can overcome resistance. Doxorubicin stops DNA replication. The accumulation and distribution of doxorubicin in cells is pH-dependent. Synergistic effects of the lichen compounds and lapatinib or doxorubicin were estimated, using the CalcuSyn software, in the breast cancer cell lines, SK-BR-3 (HER2+, high levels of FASN) T-47D (P53-mutated) and MCF7. Significant synergistic effects were obtained in SK-BR-3 cell line after combined treatment with PA/lapatinib, and in T-47D cells but at higher concentrations. No synergism was seen in MCF7 cells. Treatment with UA/doxorubicin showed marked synergism at all tested concentrations in T-47D cells; none was seen in SK-BR-3 cells. Synergism between a lichen compound and a drug can be related to metabolic effects. Moreover the synergistic effects appear to be cell-type-dependent. Citation Format: Margret Bessadottir, Edda A. Skuladottir, Sindri Baldursson, Sesselja Omarsdottir, Helga M. Ögmundsdottir. Lichen-derived metabolites show synergistic effects in combination with lapatinib and doxorubicin against breast cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 788. doi:10.1158/1538-7445.AM2014-788
176. In Vivo Selective Enhancement of Correction of Human X-Linked Chronic Granulomatous Disease Neutrophils in NOD/SCID Mice Transplanted with CD34+ Stem Cells Transduced with a Bicistronic gp91phox/Benzyl Guanine Resistant Methylguanine Methyltransferase Vector
Authors: Uimook Choi, Kouhei Yamashita, Lanise Caldwell, Harry L. Malech
Journal: Molecular Therapy (2004)

X-linked chronic granulomatous disease (X-CGD) results from a deficiency of gp91phox, the NADPH/flavin/heme binding component of the phagocyte oxidase. Correction of gp91phox expression provides no selective growth or survival advantage to hematopoietic stem cells (HSC). Achievement of clinical benefit from CGD gene therapy may require co-expressing a gene conferring a selective growth advantage at the stem cell level together with therapeutic gp91phox gene. Methylguanine methyltransferase (MGMT) can repair alkylation of DNA resulting from 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) treatment. Human P140K mutant MGMT (hMGMT*) is highly resistant to inactivation by the irreversible inhibitor substrate, O6-benzylguanine (BG), while retaining DNA repair capacity, thus protecting HSC from synergistic cytotoxicity of sequential treatment with BG and BCNU. The advantage of this selective system as shown by others is that it can be applied in vivo to enhance the percent of cells marked with hMGMT*. We used a bicistronic onco-retrovirus bicistronic vector, RD114 pseudotyped MFGS-gp91phox-IRES-hMGMT*, to transduce human CD34+ cells from patients with X-CGD. After transplant into NOD/SCID mice, we demonstrated in vivo selective enhancement of gp91phox expression in human neutrophils arising in these mice following treatment with BG/BCNU 20/6 mg/kg at week 4 and week 5 post transplant. 90% of the ex vivo transduced human X-CGD CD34+ cells expressed gp91phox transgene. Neutrophils differentiating from these transduced cells in culture demonstrate a high level of correction of oxidase activity, and this correction can be further enhanced by ex vivo selection with BG/BCNU. Transplant of the transduced X-CGD CD34+ cells into NOD/SCID mice was followed by BG/BCNU treatment of some animals. NOD/SCID mice were sacrificed at 7 weeks to evaluate gp91phox transgene expression and oxidase activity without or with in vivo BG/BCNU treatment. Average human cell engraftment (human CD45+) in mice not treated with BG/BCNU was 18.5 13 % versus 29 13 % in mice treated with BG/BCNU, a trend that did not reach statistical significance. However, in these experiments only 0.8 0.6 % of human neutrophils in bone marrow of untreated mice (CD45+/high side scatter) expressed gp91phox, but 11.4 4.6 % of human neutrophils in BG/BCNU mice expressed gp91phox transgene, a difference that was highly significant (p < 0.01). Thus we used the NOD/SCID mouse system to demonstrate for the first time that hMGMT* linked to a human therapeutic gene in a retrovirus vector can be used to enhance correction of a human blood disorder (X-CGD) following in vivo treatment with BG/BCNU.