tbuckley/cabot-search huggingface dataset:
Phosphoglycerate kinase San Francisco: A new variant associated with hemolytic anemia but not with neuromuscular manifestations
Authors: M. S. Guis, N. Karadsheh, W. C. Mentzer
Journal: American Journal of Hematology (1987)

Abstract Phosphoglycerate kinase deficiency is a rare, x‐linked glycolytic defect that, when severe, can be associated with hemolytic anemia, rhabdomyolysis, or neurological disorders. We report here a new phosphoglycerate kinase variant discovered in a boy with severe hemolytic anemia but no evidence of neuromuscular disease or developmental delay. The biochemical properties of the variant enzyme (greatly increased k m ATP and k m 3‐phosphoglycerate; normal pH optimum, electrophoretic mobility, and substrate specificity; resistance to heat inactivation) establish its uniqueness. Separation of light and dense red cells by centrifugation showed no greater loss of phosphoglycerate kinase activity in dense (“old”) variant cells than in normal cells. We postulate that the striking stability of the variant enzyme allows cells capable of protein synthesis to accumulate sufficient enzyme to limit neuromuscular sequelae.
Recycling endosomes supply cardiac pacemaker channels for regulated surface expression
Authors: Nadine Hardel, Nadine Harmel, Gerd Zolles, Bernd Fakler, Nikolaj Klöcker
Journal: Cardiovascular Research (2008)

AimsCellular excitability is not only determined by the type but also by the number of ion channels in the plasma membrane. Recent evidence indicates that cell surface expression of cardiac pacemaker channels might be controlled beyond the level of biosynthesis by regulating their surface transport. However, neither the underlying trafficking pathways nor their molecular control have yet been investigated.
An unusual case of diaphragm paralysis
Authors: S. Freilich, J. C. Janssen, M. I. Polkey
Journal: Thorax (2010)

Our patient was a 62-year-old retired accountant of previous good health. He was not taking any medications and had no family history of neurological disease. He was involved in a minor road traffic accident in which his car was shunted from behind. No immediate injuries were sustained; however, he presented to his general practitioner 4 days later with lumbar spine discomfort. He was prescribed a codeine–paracetamol combination pill and diclofenac. Immediately after taking the first dose of these medications he developed severe dizziness and marked vomiting, which culminated in mild haematemesis, indicative of a Mallory–Weiss tear. Subsequently he discovered that he was dyspnoeic lying flat. He presented to his local emergency department with symptoms including marked orthopnoea, and dyspnoea on water immersion past his costal margin and on bending forward.

Physical examination showed gross paradoxical abdominal motion and mild breathlessness when recumbent. Respiratory system, some left basal crackles; cardiovascular system, normal; abdomen, normal; neurology, normal.

Arterial blood gas measurements showed a Pao2 of 11.1 kPa and a Paco2 of 5.1 kPa. A chest radiograph showed an elevated left hemidiaphragm with some atelectasis above it. A CT pulmonary angiogram excluded any diaphragmatic rupture or pulmonary embolus as an underlying cause of orthopnoea. His sniff nasal inspiratory pressure (SNIP) was measured at 22 cm H2O. Detailed testing showed no response to bilateral anterior magnetic phrenic nerve stimulation or to right unilateral phrenic nerve stimulation, with a greatly reduced response to left-sided stimulation (twitch transdiaphragmatic pressure 1.3 cm H2O; normal >8 cm H2O). Pulmonary function tests (performed in …
Effects of Controlled-Release Metoprolol on Total Mortality, Hospitalizations, and Well-being in Patients With Heart Failure
Authors: Åke Hjalmarson, Sidney Goldstein, Björn Fagerberg, Hans Wedel, Finn Waagstein, John Kjekshus, John Wikstrand, Dia El Allaf, Jirí Vítovec, Jan Aldershvile, Matti Halinen, Rainer Dietz, Karl-Ludwig Neuhaus, András Jánosi, Gudmundur Thorgeirsson, Peter H. J. M. Dunselman, Lars Gullestad, Jerzy Kuch, Johan Herlitz, Peter Rickenbacher, Stephen Ball, Stephen Gottlieb, Prakash Deedwania, None for the MERIT-HF Study Group
Journal: JAMA (2000)

HRONIC HEART FAILURE IS Acommon disease that has a poor prognosis and periods of incapacitating symptoms necessitating recurrent hospital admis-sions. 1,2The most common modes of death are sudden death or death from worsening heart failure. 3The discovery of the pathophysiological impor-
Investigating the early-life determinants of illness in Africa: the Drakenstein Child Health Study
Authors: H J Zar, W Barnett, L Myer, D J Stein, M P Nicol
Journal: Thorax (2014)

Respiratory disease is the predominant cause of illness in children globally. We describe a unique multidisciplinary South African birth cohort, the Drakenstein Child Health Study (DCHS), to investigate the incidence, risk factors, aetiology and long-term impact of early lower respiratory tract infection (LRTI) on child health. Pregnant women from a poor, peri-urban community with high exposure to infectious diseases and environmental risk factors are enrolled with 1000 mother-child pairs followed for at least 5 years. Biomedical, environmental, psychosocial and demographic risk factors are longitudinally measured. Environmental exposures are measured using monitors placed at home visits. Lung function is measured in children at 6 weeks, annually and during LRTI episodes. Microbiological investigations including microbiome and multiplex PCR measures are done longitudinally and at LRTI episodes. The DCHS is a unique African birth cohort study that uses sophisticated measures to comprehensively investigate the early-life determinants of child health in an impoverished area of the world.
Ovarian ablation by radiotherapy; is it still an option for the ovarian function suppression in endocrine responsive premenopausal breast cancer patients?.
Authors: NS Bese, A Iribas, DC Oksuz, G Atkovar, A Ober
Journal: Cancer Research (2009)

Abstract Abstract #5137 Background; Although surgical or medical ovarian ablation is likely to be the treatment of choice at the current time, radiation ablation (RA) can be still a resonable alternative. Data regarding the use of pelvic radiotherapy (RT) for ovarian ablation is very limited and in 10thSt Gallen consensus meeting, ovarian radiation was overwhelmingly rejected. In this retrospective study we evaluated the efficacy of RT for ovarian function suppression in 118 premenopausal breast cancer patients.&amp;#x2028; Materials and Methods; 153 breast cancer patients had RA between the years 1979 and 2002 at the single center where this study was performed. 19 patients who received chemotherapy within 12 months of RA, and 16 patients who were lost to follow-up within 6 months following RA, were not included into the analyses. All patients were premenopausal and the median age at the initiation of RA was 39 years (range, 21- 52 years). 96 of 118 patients (82%) underwent RA for metastatic disease, 17 patients (14%) received RA as the systemic treatment after locoregional recurrences and 5 patients (4%) had RA as an adjuvant treatment. 97 patients (82%) received only RA as their systemic treatment, 20 patients (17%) had RA with tamoxifen and one patient (1%) had RA with aromatase inhibitors. RT was given with either Co-60 or 15 MV photons of the linear accelerator. A modified pelvic volume was irradiated with opposing anterior and posterior fields, and the dose was prescribed to midplane. The median total dose used for RA was 15Gy in 4 fractions (range 5Gy single fraction-36Gy in 18 fractions).&amp;#x2028; Results; As the efficacy of RA, data regarding the menstrual status were collected. Amenorrhea was noted in 113 of 118 patients (96%) in 6 months following RA. 88 patients (75%) experienced amenorrhea in 2 months after pelvic RT. 5 patients (4%) who had still normal menstrual functioning after 6 months of RA had estrodiol and follicle stimulating hormone measurements. As they were found to have premenopausal levels, 3 of them received surgical and 2 of them received medical ablation. No acute Grade 3 or 4 (according to the Radiation Therapy Oncology Group radiation morbidity scoring criteria) toxicities were noted. With a median follow-up of 24,5 months (range; 6-167 months), no late severe complications that could be attributable to RT were reported. The total RT dose (more than 15Gy) were found to be significant on the rate of ovarian ablation with Mann Whithney U-test (p=0.02).&amp;#x2028; Conclusion: Ovarian ablation was achieved with a rate of 96% without any major acute and late toxicity using pelvic RT. It should be considered as an option for endocrine responsive premenopausal breast cancer patients and can be easily delivered when postoperative or palliative irradiation is given. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5137.
Divalproex Treatment for Youth With Explosive Temper and Mood Lability: A Double-Blind, Placebo-Controlled Crossover Design
Authors: S J Donovan, J W Stewart, E V Nunes, F M Quitkin, M Parides, W Daniel, E Susser, D F Klein
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: The authors sought to replicate open-label findings showing that specific criteria for explosive temper and mood lability identify disruptive youth who improve while receiving the anticonvulsant divalproex sodium.METHOD: Twenty outpatient children and adolescents (ages 10–18) with a disruptive behavior disorder (oppositional defiant disorder or conduct disorder) met the specific criteria for explosive temper and mood lability. They received 6 weeks of divalproex treatment and 6 weeks of placebo by random assignment. Independent evaluators blind to group assignment assessed response at the end of each phase.RESULTS: At the end of phase 1, eight of 10 subjects had responded to divalproex; zero of 10 had responded to placebo. Of the 15 subjects who completed both phases, 12 has superior response taking divalproex.CONCLUSIONS: This preliminary study replicates open-label findings showing that divalproex is an efficacious treatment for explosive temper and mood lability in disruptive children and adolescents.
Adiponectin Deficiency Limits Tumor Vascularization in the MMTV-PyV-mT Mouse Model of Mammary Cancer
Authors: Martin S. Denzel, Lionel W. Hebbard, Gregory Shostak, Lawrence Shapiro, Robert D. Cardiff, Barbara Ranscht
Journal: Clinical Cancer Research (2009)

Abstract Purpose: High levels of the fat-secreted cytokine adiponectin (APN) are present in the circulation of healthy people, whereas low levels correlate with an increased incidence of breast cancer in women. The current study experimentally probes the physiologic functions of APN in mammary cancer in a newly generated genetic mouse model. Experimental Design: We established an APN null mouse model of mammary cancer by introducing the polyoma virus middle T (PyV-mT) oncogene expressed from mouse mammary tumor virus (MMTV) regulatory elements into APN null mice. MMTV-PyV-mT–induced tumors resemble ErbB2–amplified human breast cancers. We monitored tumor onset, kinetics, and animal survival, and analyzed vascular coverage, apoptosis, and hypoxia in sections from the primary tumors. Metastatic spreading was evaluated by analyses of the lungs. Results: APN prominently localized to the vasculature in human and mouse mammary tumors. In APN null mice, MMTV-PyV-mT–induced tumors appeared with delayed onset and exhibited reduced growth rates. Affected animals survived control tumor-bearing mice by an average of 21 days. Pathologic analyses revealed reduced vascularization of APN null tumors along with increased hypoxia and apoptosis. At the experimental end point, APN null transgenic mice showed increased frequency of pulmonary metastases. Conclusion: The current work identifies a proangiogenic contribution of APN in mammary cancer that, in turn, affects tumor progression. APN interactions with vascular receptors may be useful targets for developing therapies aimed at controlling tumor vascularization in cancer patients.
AN EXPERIMENTAL METHOD FOR SCREENING ANTIPRURITIC AGENTS.
Authors: G. V. JOGLEKAR, M. B. BHIDE, J. H. BALWANI
Journal: British Journal of Dermatology (1963)

Journal Article AN EXPERIMENTAL METHOD FOR SCREENING ANTIPRURITIC AGENTS. Get access G. V. JOGLEKAR, G. V. JOGLEKAR Department of Pharmacology, B. J. Medical College, Poona 1, India Search for other works by this author on: Oxford Academic Google Scholar M. B. BHIDE, M. B. BHIDE Department of Pharmacology, B. J. Medical College, Poona 1, India Search for other works by this author on: Oxford Academic Google Scholar J. H. BALWANI J. H. BALWANI Department of Pharmacology, B. J. Medical College, Poona 1, India Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 75, Issue 3, 1 March 1963, Pages 117–119, https://doi.org/10.1111/j.1365-2133.1963.tb13948.x Published: 01 March 1963
Fenretinide Activity in Retinoid-Resistant Oral Leukoplakia
Authors: Scott M. Lippman, J. Jack Lee, Jack W. Martin, Adel K. El-Naggar, Xiaochun Xu, Dong M. Shin, Margaret Thomas, Li Mao, Herbert A. Fritsche, Xian Zhou, Vassiliki Papadimitrakopoulou, Fadlo R. Khuri, Hai Tran, Gary L. Clayman, Walter N. Hittelman, Waun Ki Hong, Reuben Lotan
Journal: Clinical Cancer Research (2006)

Abstract Purpose: To test the hypothesis that the retinamide N-(4-hydroxyphenyl)retinamide (fenretinide) would be clinically active potentially via receptor-independent apoptosis and receptor-dependent effects in natural retinoid-resistant oral leukoplakia patients—the first test of this hypothesis in any in vivo setting. Experimental Design: A phase II trial of fenretinide (200 mg/d for 3 months) in oral leukoplakia patients who had not responded (de novo resistance) or who had responded and then relapsed (acquired resistance) to previous treatment with natural retinoids. We analyzed apoptosis via the terminal deoxynucleotidyl transferase–mediated nick end labeling in situ DNA fragmentation assay. Results: We accrued 35 evaluable patients with retinoid-resistant oral leukoplakia, 12 (34.3%) had partial responses to fenretinide (95% confidence interval, 19.2-52.4%), and response was associated with acquired resistance to natural retinoids (P = 0.015, Fisher's exact test). Nine responders progressed within 9 months of stopping fenretinide. Toxicity was minimal and compliance was excellent. Mean apoptosis values (SE) increased from 0.35% (0.25%) at baseline to 1.18% (0.64%) at 3 months (P = 0.001, sign test); this increase did not correlate with clinical response. The increases in 3-month mean serum concentrations of fenretinide (0.23 μmol/L) and N-(4-methoxyphenyl)retinamide (0.57 μmol/L) correlated with decreased retinol concentrations [Spearman correlation coefficient of −0.57 (P = 0.001) and −0.43 (P = 0.01), respectively]. Conclusions: Low-dose fenretinide was clinically active and produced a small increase in apoptosis in retinoid-resistant oral leukoplakia.
Emphysematous Cystitis due to Clostridium perfringens
Authors: Timothy E. West
Journal: JAMA (1981)

ANAEROBIC bacteria are infrequent pathogens of the urinary tract. Emphysematous cystitis results most commonly from infection with a gasforming aerobic organism such as<i>Escherichia coli</i>.<sup>1</sup>We describe a diabetic patient with emphysematous cystitis due to the gas-forming anaerobe<i>Clostridium perfringens</i>. <h3>Report of a Case</h3> A 72-year-old woman was admitted to the Charleston County Hospital in December 1979 for evaluation of weakness and intermittent, cramping, periumbilical pain of two months' duration. She reported that the pain decreased after voiding and denied any dysuria, urgency, urinary incontinence, or pneumaturia. She was a well-controlled diabetic whose condition was maintained with 20 units of isophane insulin suspension daily. Blood glucose value on admission was 86 mg/dL; hematocrit reading, 31 vol%; and WBC count, 7,700 cells per cubic millimeter, with 41% neutrophils. Findings from urinalysis demonstrated 35 to 45 WBCs per cubic millimeter and were otherwise normal. An abdominal roentgenogram showed an enlarged bladder
Vascular endothelial growth factor triggers signaling cascades mediating multiple myeloma cell growth and migration
Authors: Klaus Podar, Yu-Tzu Tai, Faith E. Davies, Suzanne Lentzsch, Martin Sattler, Teru Hideshima, Boris K. Lin, Deepak Gupta, Yoshihito Shima, Dharminder Chauhan, Constantine Mitsiades, Noopur Raje, Paul Richardson, Kenneth C. Anderson
Journal: Blood (2001)
Addition of cetuximab to first-line chemotherapy in patients with advanced non-small-cell lung cancer: a cost–utility analysis
Authors: M. Joerger, K. Matter-Walstra, M. Früh, U. Kühnel, T. Szucs, B. Pestalozzi, M. Schwenkglenks
Journal: Annals of Oncology (2010)

Adding cetuximab to standard chemotherapy results in a moderate increase of overall survival in patients with advanced non-small-cell lung cancer (NSCLC), but the cost-effectiveness is unknown.A Markov model was constructed based on the results of the First-Line ErbituX in lung cancer randomized trial, adding cetuximab to cisplatin-vinorelbine first-line chemotherapy in patients with advanced NSCLC. The primary outcome was the incremental cost-effectiveness ratio (ICER) of adding cetuximab, expressed as cost per quality-adjusted life year (QALY) gained, and relative to a willingness-to-pay threshold of €60 000/QALY. The impact of cetuximab intermittent dosing schedules on the ICER was also evaluated.Adding cetuximab to standard chemotherapy leads to a gain of 0.07 QALYs per patient at an additional cost of €26 088. The ICER for adding cetuximab to chemotherapy was €376 205 per QALY gained. Intermittent cetuximab dosing schedules resulted in ICERs per QALY gained between €31 300 and €83 100, under the assumption of equal efficacy.From a health economic perspective, the addition of cetuximab to standard first-line chemotherapy in patients with epidermal growth factor receptor-expressing advanced NSCLC cannot be recommended to date, due to a high ICER compared with other health care interventions. Treatment schedules resulting in more favorable cost-utility ratios should be evaluated.
ALS-associated mutation FUS-R521C causes DNA damage and RNA splicing defects
Authors: Haiyan Qiu, Sebum Lee, Yulei Shang, Wen-Yuan Wang, Kin Fai Au, Sherry Kamiya, Sami J. Barmada, Steven Finkbeiner, Hansen Lui, Caitlin E. Carlton, Amy A. Tang, Michael C. Oldham, Hejia Wang, James Shorter, Anthony J. Filiano, Erik D. Roberson, Warren G. Tourtellotte, Bin Chen, Li-Huei Tsai, Eric J. Huang
Journal: Journal of Clinical Investigation (2014)

Autosomal dominant mutations of the RNA/DNA binding protein FUS are linked to familial amyotrophic lateral sclerosis (FALS); however, it is not clear how FUS mutations cause neurodegeneration. Using transgenic mice expressing a common FALS-associated FUS mutation (FUS-R521C mice), we found that mutant FUS proteins formed a stable complex with WT FUS proteins and interfered with the normal interactions between FUS and histone deacetylase 1 (HDAC1). Consequently, FUS-R521C mice exhibited evidence of DNA damage as well as profound dendritic and synaptic phenotypes in brain and spinal cord. To provide insights into these defects, we screened neural genes for nucleotide oxidation and identified brain-derived neurotrophic factor (Bdnf) as a target of FUS-R521C–associated DNA damage and RNA splicing defects in mice. Compared with WT FUS, mutant FUS-R521C proteins formed a more stable complex with Bdnf RNA in electrophoretic mobility shift assays. Stabilization of the FUS/Bdnf RNA complex contributed to Bdnf splicing defects and impaired BDNF signaling through receptor TrkB. Exogenous BDNF only partially restored dendrite phenotype in FUS-R521C neurons, suggesting that BDNF-independent mechanisms may contribute to the defects in these neurons. Indeed, RNA-seq analyses of FUS-R521C spinal cords revealed additional transcription and splicing defects in genes that regulate dendritic growth and synaptic functions. Together, our results provide insight into how gain-of-function FUS mutations affect critical neuronal functions.
Risk of Ischemic Heart Disease in Women after Radiotherapy for Breast Cancer
Authors: Sarah C. Darby, Marianne Ewertz, Paul McGale, Anna M. Bennet, Ulla Blom-Goldman, Dorthe Brønnum, Candace Correa, David Cutter, Giovanna Gagliardi, Bruna Gigante, Maj-Britt Jensen, Andrew Nisbet, Richard Peto, Kazem Rahimi, Carolyn Taylor, Per Hall
Journal: New England Journal of Medicine (2013)

Radiotherapy for breast cancer often involves some incidental exposure of the heart to ionizing radiation. The effect of this exposure on the subsequent risk of ischemic heart disease is uncertain.We conducted a population-based case-control study of major coronary events (i.e., myocardial infarction, coronary revascularization, or death from ischemic heart disease) in 2168 women who underwent radiotherapy for breast cancer between 1958 and 2001 in Sweden and Denmark; the study included 963 women with major coronary events and 1205 controls. Individual patient information was obtained from hospital records. For each woman, the mean radiation doses to the whole heart and to the left anterior descending coronary artery were estimated from her radiotherapy chart.The overall average of the mean doses to the whole heart was 4.9 Gy (range, 0.03 to 27.72). Rates of major coronary events increased linearly with the mean dose to the heart by 7.4% per gray (95% confidence interval, 2.9 to 14.5; P<0.001), with no apparent threshold. The increase started within the first 5 years after radiotherapy and continued into the third decade after radiotherapy. The proportional increase in the rate of major coronary events per gray was similar in women with and women without cardiac risk factors at the time of radiotherapy.Exposure of the heart to ionizing radiation during radiotherapy for breast cancer increases the subsequent rate of ischemic heart disease. The increase is proportional to the mean dose to the heart, begins within a few years after exposure, and continues for at least 20 years. Women with preexisting cardiac risk factors have greater absolute increases in risk from radiotherapy than other women. (Funded by Cancer Research UK and others.).
Do Patients Benefit from Routine Follow-up to Detect Recurrences After Radical Cystectomy and Ileal Orthotopic Bladder Substitution?
Authors: Gianluca Giannarini, Thomas M. Kessler, Harriet C. Thoeny, Daniel P. Nguyen, Claudia Meissner, Urs E. Studer
Journal: European Urology (2010)