tbuckley/cabot-search huggingface dataset:
Resection of Mycotic Aneurysm of the Small-Bowel Mesentery
Authors: Michael M. Lovezzola
Journal: New England Journal of Medicine (1958)

THE following case is considered of interest because only 1 similar case could be found in the medical literature:Case ReportJ.W.B. (V.A.H. 10,928), a 34-year-old man, was admitted to the hospital on October 27, 1956, and a clinical diagnosis of subacute bacterial endocarditis was made. Blood culture demonstrated an anaerobic alpha-hemolytic streptococcus. Five weeks after admission, while he was ambulant and undergoing satisfactory convalescence, sudden abdominal pain began. Seventy-two hours after the onset of the pain he was seen in surgical consultation. Examination disclosed mild, diffuse spasm without definite local abdominal tenderness. There was mild rebound and high anterior . . .
Identification of the Genes Involved in Enhanced Fenretinide-Induced Apoptosis by Parthenolide in Human Hepatoma Cells
Authors: Jeong-Hyang Park, Lan Liu, In-Hee Kim, Jong-Hyun Kim, Kyung-Ran You, Dae-Ghon Kim
Journal: Cancer Research (2005)

Fenretinide (N-4-hydroxyphenyl retinamide, 4HPR) is a synthetic anticancer retinoid that is a well-known apoptosis-inducing agent. Recently, we observed that the apoptosis induced by fenretinide could be effectively enhanced in hepatoma cells by a concomitant treatment with parthenolide, which is a known inhibitor of nuclear factor-kappaB (NF-kappaB). Furthermore, treatment with fenretinide triggered the activation of NF-kappaB during apoptosis, which could be substantially inhibited by parthenolide, suggesting that NF-kappaB activation during fenretinide-induced apoptosis has an antiapoptotic effect. This study investigated the molecular mechanism of this apoptotic potentiation by NF-kappaB inhibition. The genes involved in the enhanced fenretinide-induced apoptosis by parthenolide were identified using the differential display-PCR method and subsequent Northern blot or semiquantitative reverse transcriptase PCR analysis. This study identified 35 apoptosis-related genes including 12 unknown genes that were either up- or down-regulated by parthenolide. Interestingly, one up-regulated gene (HA1A2) was isolated and cloned from the liver cDNA, and was found to be identical to ANKRD1, which is also referred to as the CARP gene. Compared with controls treated with an empty vector or with antisense cDNA, the ectopic expression of ANKRD1 led to reduced colony formation and to enhanced apoptotic cell death in hepatoma cells. These results suggest that ANKRD1 and the other genes, whose expressions were substantially modulated by the parthenolide-mediated inhibition of NF-kappaB activation, play roles in the enhanced drug-induced apoptosis. In addition, this study suggests that those identified genes may be useful in anticancer strategies against hepatoma.
BM-15 * TARGETING MEK IS A NOVEL AND EFFECTIVE TREATMENT STRATEGY OF LUNG CNS METASTASIS
Authors: K. N. Johnson, G. Gooden, P. Gonzalez, M. Sepulveda, L. Gorgol, E. F. Petricoin, M. Pierobon, S. Byron, J. Glen, M. Ahluwalia, M. Bernstein, S. A. Toms, B. Salhia
Journal: Neuro-Oncology (2014)

There is an urgent need to introduce novel therapies that prevent death due to lung cancer CNS metastasis, which remains a clinically unmet need. Targeted molecular therapies and prophylactic measures might shift the current strategy and improve outcomes. Accordingly our study has focused on identifying novel monotherapies and combination therapies that are based on causal, actionable molecular derangements in lung cancer CNS metastasis, and which can be effectively targeted within the context of the brain microenvironment. We have recently established 6 novel patient-derived cell-lines and matching mouse xenograft models of lung CNS metastasis for preclinical testing of novel therapeutic approaches. Cell-lines were implanted intra-cardiacally for confirmation of CNS homing potential. Therapeutic selections for in vivo testing were based on systems biology-based analyses of the matching clinical material using genomic, epigenomic and phosphoproteomic analyses, which revealed systemic biochemical changes that are druggable. Matching datasets were generated for each cell-line and xenograft to ensure the effectiveness of models in representing the human disease. Primary lung tumors were analyzed when available (2/6 cases). Data analysis revealed defects in KRAS activation due to amplifications, mutations and signaling. Therefore, we proceeded to examine the anti-tumor effects of the MEK inhibitor, PD032591 for in vivo targeting of KRAS. There was >90% inhibition of tumor growth and prolonged survival of animals when treated for 14-30 days with PD032591 in an ectopic or orthotopic setting. Signaling architecture was analyzed pre and post treatment and demonstrated strong attenuation of phospho-ERK without concomitant activation of compensatory mechanisms. We are also currently performing a comprehensive functional screen to identify a synergistic combination strategy for use with PD032591 by testing over 300 clinically available compounds. This first-of-its-kind study has demonstrated a strong preclinical rationale for targeting MEK in lung cancer CNS metastasis with KRAS alterations.
Abstract 3323: E7449, a potent inhibitor of PARP 1 and 2, is active in acute myeloid leukemia.
Authors: Sharon McGonigle, Zhihong Chen, Jiayi Wu, Donna Kolber-Simonds, Shannon McGrath, Karen TenDyke, Zichun Wang, Kenichi Nomoto
Journal: Cancer Research (2013)

Abstract Leukemic cells, like many other cancer cells, are often deficient in DNA repair capacity. PARP inhibitors have demonstrated synthetic lethality in cancer cells with defective DNA repair. E7449 is an orally bioavailable, potent, small molecule inhibitor of poly(ADP-ribose) polymerase (PARP)1 and PARP2. In this study we describe the therapeutic potential of the PARP inhibitor E7449 in acute myeloid leukemia (AML). E7449 inhibited proliferation of leukemia cells in a long term in vitro growth inhibition assay in a panel of leukemic cell lines. The MV-4-11 AML cell line was identified as particularly sensitive to E7449 PARP inhibition, and induction of apoptosis was observed in these cells. An in vivo survival model of acute myeloid leukemia (AML) was established in NSG mice using MV-4-11-luc2/AcGFP human AML cells. Daily dosing of E7449 at 100 mg/kg resulted in statistically significant anticancer activity in this model. Reduced disease burden as measured by luciferase signal was observed. This decrease in leukemic load also translated into a statistically significant survival benefit in E7449 treated mice. In AML cells, high P-glycoprotein (P-gp) expression is often observed, particularly in older patients, and this often leads to resistance to typical therapies. E7449 anti-proliferative activity was assessed in paired murine leukemia cells with basal (P388/S) and overexpressed P-gp protein (P388/VMDRC.04). E7449 effectively inhibited growth of the high P-gp expressing cells as well as the parent P388/S cells, with no significant difference in the presence or absence of verapamil, in contrast to data obtained for the P-gp substrate doxorubicin. These data demonstrate that E7449 is not a substrate for P-gp transport. Importantly, E7449 also significantly inhibited proliferation of primary patient AML cells ex vivo. In addition, E7449 proved highly potent at inhibiting colony formation in the majority of primary patient AML specimens assessed in long term (14 day) clonogenic survival assays. Studies to discern the mechanism underlying sensitivity to E7449 in AML cells are underway. Conclusion: In this study, E7449 possessed potent anti-cancer activity against AML cell lines and primary patient AML cells in vitro and ex vivo, it was not a substrate for P-gp transport, and it reduced disease burden and increased survival in an AML in vivo model. These data support the assessment of E7449 as a therapy for AML in the clinic. Citation Format: Sharon McGonigle, Zhihong Chen, Jiayi Wu, Donna Kolber-Simonds, Shannon McGrath, Karen TenDyke, Zichun Wang, Kenichi Nomoto. E7449, a potent inhibitor of PARP 1 and 2, is active in acute myeloid leukemia. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3323. doi:10.1158/1538-7445.AM2013-3323
Exercise-induced pulmonary vasoconstriction during combined blockade of nitric oxide synthase and beta adrenergic receptors.
Authors: D W Kane, T Tesauro, T Koizumi, R Gupta, J H Newman
Journal: Journal of Clinical Investigation (1994)

We studied the effects of inhibition of nitric oxide (NO) (endothelium-derived relaxation factor) synthase in combination with alpha and beta adrenergic receptor blockade on pulmonary vascular tone during exercise. In paired studies, we exercised sheep on a treadmill at a speed of 4 mph, and measured blood flow and pressures across the pulmonary circulation with and without inhibition of NO synthase (N omega-nitro-L-arginine 20 mg/kg intravenous [i.v.]), alpha receptor blockade (phentolamine 5 mg i.v.), beta receptor blockade (propranolol 1 mg i.v.), and combined alpha and beta receptor blockade. Activation of both types of adrenergic receptors occurs with exercise, and because increased release in NO is hypothesized to occur during exercise, these studies were designed to determine the magnitude of effect and interactions of these competing dilator and constrictor influences. We found that inhibition of NO synthase raised pulmonary vascular resistance (PVR) at rest and that, although a reduction in PVR occurred with exercise from this new baseline, vasoconstriction persisted. Combined beta blockade and NO synthase inhibition unmasked unopposed alpha vasoconstriction; PVR rose at rest and continued to rise with exercise; and mean pulmonary arterial pressures approached very high levels, 43.8 +/- 4.4 cmH2O. Using a distal wedged pulmonary artery catheter technique, most of the vasoconstriction was found to be in vessels upstream from small pulmonary veins. During exercise in sheep there appears to be a high degree of alpha and beta adrenergic-mediated tone in the pulmonary circulation. Endogenous production of NO actively dilates pulmonary vessels at rest and opposes potent alpha-mediated pulmonary vasoconstriction during exercise.
Phosphatidylinositol-3-OH kinase and nutrient-sensing mTOR pathways control T lymphocyte trafficking
Authors: Linda V Sinclair, David Finlay, Carmen Feijoo, Georgina H Cornish, Alex Gray, Ann Ager, Klaus Okkenhaug, Thijs J Hagenbeek, Hergen Spits, Doreen A Cantrell
Journal: Nature Immunology (2008)
Holmes or Spade?
Authors: Samuel Vaisrub
Journal: JAMA (1977)

To the patient, an illness is a dramatic, often tragic chapter in a long autobiography. To the diagnostician, however, it is primarily a mystery story in which he is the detective. As such, he may wish to draw some parallels from the behavior of his counterpart, the professional sleuth of popular fiction.  In a recent essay, the master dichotomist C. P. Snow 1 classified detective stories into two species, the classical and the romantic. In the former, the detective solves his problem by deductions based on observation and logic, much as the scientist solves his by the scientific process. Curious, observant, and impeccably logical, he does not indulge in psychological analysis, nor does he display any emotional involvement, let alone righteous indignation. His satisfaction, as well as that of the reader, comes from solving a mystery, from bringing order into a disorderly situation.  This type of detective was predominant in the
Prostaglandins and pruritus*
Authors: C.R. LOVELL, PATRICIA A. BURTON, ETHEL H.L. DUNCAN, J.L. BURTON
Journal: British Journal of Dermatology (1976)

Journal Article Prostaglandins and pruritus Get access C.R. LOVELL, C.R. LOVELL Department of Dermatology, Bristol Royal Infirmary, Bristol Search for other works by this author on: Oxford Academic Google Scholar PATRICIA A. BURTON, PATRICIA A. BURTON Department of Dermatology, Bristol Royal Infirmary, Bristol Search for other works by this author on: Oxford Academic Google Scholar ETHEL H.L. DUNCAN, ETHEL H.L. DUNCAN Department of Community Health, University of Bristol, Bristol Search for other works by this author on: Oxford Academic Google Scholar J.L. BURTON J.L. BURTON Department of Dermatology, Bristol Royal Infirmary, Bristol Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 94, Issue 3, 1 March 1976, Pages 273–275, https://doi.org/10.1111/j.1365-2133.1976.tb04383.x Published: 01 March 1976
Direct reprogramming of induced neural progenitors: a new promising strategy for AD treatment
Authors: Siqiang Lai, Min Zhang, Dongsheng Xu, Yiying Zhang, Lisha Qiu, Changhai Tian, Jialin Charlie Zheng
Journal: Translational Neurodegeneration (2015)

Alzheimer’s disease (AD) is a prominent form of dementia, characterized by aggregation of the amyloid β-peptide (Aβ) plaques and neurofibrillary tangles, loss of synapses and neurons, and degeneration of cognitive functions. Currently, although a variety of medications can relieve some of the symptoms, there is no cure for AD. Recent breakthroughs in the stem cell field provide promising strategies for AD treatment. Stem cells including embryonic stem cells (ESCs), neural stem cells (NSCs), mesenchymal stem cells (MSCs), and induced pluripotent stem cells (iPSCs) are potentials for AD treatment. However, the limitation of cell sources, safety issues, and ethical issues restrict their applications in AD. Recently, the direct reprogramming of induced neural progenitor cells (iNPCs) has shed light on the treatment of AD. In this review, we will discuss the latest progress, challenges, and potential applications of direct reprogramming in AD treatment.
Exposure assessment for endocrine disruptors: some considerations in the design of studies.
Authors: Carol Rice, Linda S Birnbaum, James Cogliano, Kathryn Mahaffey, Larry Needham, Walter J Rogan, Frederick S vom Saal
Journal: Environmental Health Perspectives (2003)

In studies designed to evaluate exposure-response relationships in children's development from conception through puberty, multiple factors that affect the generation of meaningful exposure metrics must be considered. These factors include multiple routes of exposure; the timing, frequency, and duration of exposure; need for qualitative and quantitative data; sample collection and storage protocols; and the selection and documentation of analytic methods. The methods for exposure data collection and analysis must be sufficiently robust to accommodate the a priori hypotheses to be tested, as well as hypotheses generated from the data. A number of issues that must be considered in study design are summarized here.
Superoxide dismutase reduces reperfusion arrhythmias but fails to salvage regional function or myocardium at risk in conscious dogs.
Authors: J Nejima, D R Knight, J T Fallon, N Uemura, W T Manders, D R Canfield, M V Cohen, S F Vatner
Journal: Circulation (1989)

To determine if oxygen free radical scavengers administered before coronary artery reperfusion can limit reperfusion arrhythmias, increase the return of regional function in ischemic myocardium, and reduce tissue necrosis at 1 week after 90-minute coronary artery occlusion and reperfusion, conscious dogs were treated with superoxide dismutase (SOD) and catalase before and for 1 hour after coronary artery reperfusion. Another group was treated with recombinant SOD (rSOD) because the commercially available SOD and catalase contained endotoxin. The conscious dogs were studied 3-4 weeks after implanting left ventricular pressure gauges, ultrasonic wall thickness gauges in the posterior left ventricular wall, left atrial catheters, and arterial catheters, Doppler flow transducers, and hydraulic occluders on the left circumflex coronary artery. The only beneficial effect observed was that the number of arrhythmic beats per minute in the rSOD-treated group was significantly lower (p less than 0.05) when compared with a control group after coronary artery reperfusion. Treatment neither increased the amount of recovery of wall thickening in the ischemic zone nor reduced infarct size when expressed either as a percentage of the area at risk or as a function of collateral blood flow in the ischemic zone. For example, infarct size as a percentage of the area at risk was 32.6 +/- 5.8%, 37.4 +/- 6.4%, 28.3 +/- 5.1% in the control, SOD and catalase-, and rSOD-treated groups, respectively. Thus, although treatment with oxygen free radical scavengers invoked a transient reduction in the number of reperfusion arrhythmias, this treatment in conscious dogs failed to improve regional myocardial dysfunction or reduce the amount of necrosis when compared with a control group. The lack of a sustained salutary effect may indicate that longer periods of treatment with free radical scavengers are required in chronic preparations.
Corticosteroids and Growth
Authors: John N. Loeb
Journal: New England Journal of Medicine (1976)

One the most conspicuous effects of the glucocorticoid hormones is an inhibition of somatic growth in immature animals. In 1940, shortly after adrenocortical hormones became available for experimental purposes, Wells and Kendall observed that small doses of cortisone promptly suppressed growth in the rat,1 and in the ensuing "steroid era" clinicians soon recognized that inhibition of growth is a prominent and often distressing problem in children treated chronically even with relatively low doses of adrenal corticosteroids. By the early 1960's several careful clinical studies had shown that as little as 45 mg of cortisone2 or 6 mg of prednisone3 per . . .
Corrigendum to “Characteristics and Outcomes of Patients with Clinical T1 Grade 3 Urothelial Carcinoma Treated with Radical Cystectomy: Results from an International Cohort” [Eur Urol 2010;57:300–9]
Authors: Hans-Martin Fritsche, Maximilian Burger, Robert S. Svatek, Claudio Jeldres, Pierre I. Karakiewicz, Giacomo Novara, Eila Skinner, Stefan Denzinger, Yves Fradet, Hendrik Isbarn, Patrick J. Bastian, Bjoern G. Volkmer, Francesco Montorsi, Wassim Kassouf, Derya Tilki, Wolfgang Otto, Umberto Capitanio, Jonathan I. Izawa, Vincenzo Ficarra, Seth Lerner, Arthur I. Sagalowsky, Mark Schoenberg, Ashish Kamat, Colin P. Dinney, Yair Lotan, Shahrokh F. Shariat
Journal: European Urology (2015)
Triiodothyronine turnover studies in euthyroid patients with autonomous thyroid nodules
Authors: R. Bianchi, G.C. Zucchelli, D. Giannessi, A. Pilo, F. Cazzuola, L. Del Corso, N. Molea, A. Carpi, M.G. Toni, G. Mariani
Journal: Metabolism (1979)
High <i>ALK</i> Receptor Tyrosine Kinase Expression Supersedes <i>ALK</i> Mutation as a Determining Factor of an Unfavorable Phenotype in Primary Neuroblastoma
Authors: Johannes H. Schulte, Hagen S. Bachmann, Bent Brockmeyer, Katleen DePreter, André Oberthür, Sandra Ackermann, Yvonne Kahlert, Kristian Pajtler, Jessica Theissen, Frank Westermann, Jo Vandesompele, Frank Speleman, Frank Berthold, Angelika Eggert, Benedikt Brors, Barbara Hero, Alexander Schramm, Matthias Fischer
Journal: Clinical Cancer Research (2011)

Genomic alterations of the anaplastic lymphoma kinase (ALK) gene have been postulated to contribute to neuroblastoma pathogenesis. This study aimed to determine the interrelation of ALK mutations, ALK expression levels, and clinical phenotype in primary neuroblastoma.The genomic ALK status and global gene expression patterns were examined in 263 primary neuroblastomas. Allele-specific ALK expression was determined by cDNA cloning and sequencing. Associations of genomic ALK alterations and ALK expression levels with clinical phenotypes and transcriptomic profiles were compared.Nonsynonymous point mutations of ALK were detected in 21 of 263 neuroblastomas (8%). Tumors with ALK mutations exhibited about 2-fold elevated median ALK mRNA levels in comparison with tumors with wild-type (WT) ALK. Unexpectedly, the WT allele was preferentially expressed in 12 of 21 mutated tumors. Whereas survival of patients with ALK mutated tumors was significantly worse as compared with the entire cohort of WT ALK patients, it was similarly poor in patients with WT ALK tumors in which ALK expression was as high as in ALK mutated neuroblastomas. Global gene expression patterns of tumors with ALK mutations or with high-level WT ALK expression were highly similar, and suggested that ALK may be involved in cellular proliferation in primary neuroblastoma.Primary neuroblastomas with mutated ALK exhibit high ALK expression levels and strongly resemble neuroblastomas with elevated WT ALK expression levels in both their clinical and molecular phenotypes. These data suggest that high levels of mutated and WT ALK mediate similar molecular functions that may contribute to a malignant phenotype in primary neuroblastoma.
Effect of ageing on cervical or vaginal cancer in Swedish women previously treated for cervical intraepithelial neoplasia grade 3: population based cohort study of long term incidence and mortality
Authors: B. Strander, J. Hallgren, P. Sparen
Journal: BMJ (2014)

<b>Objective</b> To determine factors influencing long term risks for acquiring or dying from invasive cervical or vaginal cancer in women previously treated for cervical intraepithelial neoplasia grade 3 (CIN3). <b>Design</b> Population based cohort study conducted in 1958-2008, followed up until 2009 in the Swedish Cancer Registry and Swedish Cause of Death Register, linked to the Swedish Population Register. Standardised incidence and mortality ratios were calculated for the risk of acquiring or dying from vaginal or cervical cancer, with the general female population in Sweden as reference. Relative risks in multivariable regression models were also calculated, adjusting for follow-up duration, treatment period, and age at CIN3 treatment or attained age. <b>Setting</b> Entire female population of Sweden. <b>Participants</b> 150 883 women in Sweden diagnosed and treated with CIN3 and followed up for invasive cervical or vaginal cancer, and related mortality. The cohort comprised 3 148 222 woman years. <b>Main outcome measures</b> Standardised incidence and mortality ratios, stratified by period for treatment. Relative standardised incidence ratios and standardised mortality ratios for age at acquiring or dying from cervical or vaginal cancer (attained age), adjusted for preset variables. <b>Results</b> Women previously diagnosed with CIN3 had an increased risk of dying from invasive cervical or vaginal cancer, compared with the general female population (standardised mortality ratio 2.35, 95% confidence interval 2.11 to 2.61). After age 60 years, these women had an accelerated increased risk of acquiring invasive cancer; a similar steep increase in mortality risk was seen after age 70. Regression analyses indicated that the increase in risk over time is highly attributable to ageing. <b>Conclusions</b> Women previously treated for CIN3 are at increased risk of developing and dying from cervical or vaginal cancer, compared with the general female population. The risk accelerates above age 60 years, suggesting a need for lifelong surveillance of these women.