tbuckley/cabot-search huggingface dataset:
Serum Lactic Dehydrogenase Levels in Mice During the Development of Autochthonous and Chemically Induced Tumors&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: Charles G. Crispens, Jr.
Journal: JNCI Journal of the National Cancer Institute (1963)

Serum lactic dehydrogenase (LDH) levels were determined in mice during the development of autochthonous lymphocytic leukemia and methyl-cholanthrene-induced fibrosarcomas. No correlation was found between tumor size and enzyme activity in mice with chemically induced neoplasms. Tumors were detected, by palpation, in mice with autochthonous and methyl-cholanthrene-induced tumors as much as 4 and 11 weeks, respectively, before significant increases in serum LDH were recorded. The LDH time curves for both groups of animals were similar. Maximal enzyme levels occurred 2 weeks before death; a few days before death, there was an abrupt fall in serum LDH activity. The implications of these findings, in terms of the use of LDH assays in the diagnosis of early cancers and a mechanism of serum LDH elevation, are discussed.
Bicarbonate-treated gastroendoscopy
Authors: Y. Kim
Journal: Journal of Clinical Oncology (2006)

14138 Background: Endoscopy is the most powerful examination to detect cancer. We showed efficacy and feasibility of the bicarbonate(bC)-treated gastroendoscopy (bCGE) to the patients (Y. Kim, et al. ICACT2004, Paris, France, and Y. Kim. 2006 GI Cancers Symposium, San Francisco, CA, USA). We tried an alternative preparation, divided alkalization, to modify the bCGE to less threaten patients in the examination. Methods: Enrollment-criteria was described; age 20 to 85, Performance Status 0 to 2, and no history of lidocaine (L) allergy, no wound in the oral cavity, and no severe organ dysfunction. The alkalizing-agent was 7-% sodium-bC solution (S-bC). The divided bC-treatment was shown: gurgling and swallowing a half, 10-mL, of 20-mL S-bC divided by L application into two parts, the 1st and the 2nd alkalization. pH Levels in the left pharyngeal-arch were measured. The patients were applied a deffervescent agent orally, L sprays in the pharyngeal-arch and L gel onto the pharyngeal-wall for 5-minute, and gastrointestinal-paralyzing agents intramuscularly. The reflexes (coughing and nausea), and pulse rates (PR) of the patients were monitored in the bCGE. Results: This study analyzed 9-patient in intent-to-treat method. All patients, 100%, accomplished the bCGE with the divided alkalization. Course of pH Levels, incidence of the reflexes and increasing ratio of PR were given in the table below. The divided alkalization enhanced the L effects in the pH Levels after the 2nd alkalization depending manner. Conclusions: We found the bCGE with the divided alkalization might be effective and feasible. The pH Levels after the 2nd alkalization could be the predictive factors for the successful bCGE with the divided alkalization. [Table: see text] No significant financial relationships to disclose.
A Study of the Molecular Pathology of Sucrase-Isomaltase Deficiency
Authors: Mark L. Lloyd, Ward A. Olsen
Journal: New England Journal of Medicine (1987)

The intestinal brush-border enzyme sucrase-isomaltase splits sucrose into its component monosaccharides, glucose and fructose. A deficiency of the enzyme leads to sucrose intolerance. We studied the synthesis and intracellular processing of sucrase-isomaltase, using human intestinal explants in organ culture. Pulse–chase experiments with [35S]methionine followed by immunoprecipitation, sodium dodecyl sulfate–polyacrylamide-gel electrophoresis, and fluorography of labeled sucrase-isomaltase demonstrated that the molecule was initially recognized as a protein with a relative molecular weight (Mr) of 205,000. This was apparently converted to a species of 225,000 Mr within two hours. We studied the glycosylation of the protein using endo-β-N-acetylglucosaminidase H and peptide-N4-(N-acetyl-β-glucosaminyl)-asparagine amidase digestion of oligosaccharide side chains of the two forms of sucrase-isomaltase. The results showed that the early-appearing 205-kd (kilodalton) molecule contained high-mannose asparagine-linked oligosaccharides, and that the later-appearing, 225-kd molecule contained highly processed (mature) carbohydrate chains. Studies in a patient with primary sucrase-isomaltase deficiency demonstrated normal translation and high-mannose glycosylation of the precursor but a failure in further processing of the oligosaccharides, with subsequent intracellular degradation of the glycoprotein and undetectable enzymatic activity of intestinal sucrase. Abnormal intracellular processing of the enzyme was the probable mechanism of enzyme deficiency in this patient. (N Engl J Med 1987; 316:438–42.)
Interim Results of a Multi-Center Observational Study of Current Treatment Patterns for Patients with Severe Aplastic Anemia (SAA), Very Severe Aplastic Anemia (VSAA) and Transfusion-Dependent Non-Severe Aplastic Anemia (TD-NSAA) in China
Authors: Feng-Kui Zhang, Xiao-Fan Zhu, Hai-Long He, Shun-Qing Wang, Jing-Yan Tang, Dao-Bin Zhou, Dong-Hua Zhang, Yu-Hong Zhou, De-pei Wu, Wei Li, Ling-Hui Xia, Huan-Ling Zhu, Feng Liu, Hong-Xia Shi, Xi Zhang, Fang Zhou, Jian-Da Hu, Jian-Pei Fang, Xie-Qun Chen, Tie-Zhen Ye, Ying-Min Liang, Jie Jin
Journal: Blood (2015)
Epidermal growth factor receptor copy number gain (EGFR CNG) and response to gefitinib in esophageal cancer (EC): Results of a biomarker analysis of a phase III trial of gefitinib versus placebo (TRANS-COG).
Authors: Russell D. Petty, Asa Dahle-Smith, Zosia Miedzybrodzka, Susan J. Dutton, Graeme I Murray, David Stevenson, Doreen Massie, Aileen Osbourne, Caroline Clark, Wasat Mansoor, Joyce Thompson, Mark Harrison, Anirban Chatterjee, Stephen Falk, Sean Elyan, Angel Garcia-Alonso, David Walter Fyfe, Ian Chau, Diane Collinson, David Ferry
Journal: Journal of Clinical Oncology (2014)

4016 Background: The Cancer Oesophagus Gefitinib (COG) trial randomised (1:1) 450 patients(pts) with advanced EC who had progressed after 1-2 lines of chemotherapy to gefitinib (G) or placebo (P). Improved disease control rates- DCR= RECIST CR+PR+SD at 8 weeks (P 15.6%, G 24.1%, p = 0.016), improved patient reported outcomes, and progression free survival (HR = 0.80, 95%CI 0.66, 0.96, p = 0.020) were seen with G-indicative of rapid and durable responses that were observed in a subset. We hypothesised that EGFR CNG in ECs would identify a subgroup responsive to G. Methods: EGFR CNG was determined by FISH on FFPE tumour specimens(all subject to central pathology review) and performed blind to treatment allocation and outcome. Disomy, low and high trisomy and low polysomy were classified as negative (No CNG) and high polysomy and amplification as positive(CNG). Primary endpoint was OS for G versus P in EGFR CNG and no CNG groups. Secondary endpoints were PFS, DCR and HRQL and outcomes in EGFR amplified patients only. Results: EGFR FISH results were available for 295 patients. Clinical features were not different from the COG trial . EGFR CNG was found in 46/295 (15.6%). There was no significant correlation with EGFR CNG and any clinical features which were also balanced in G and P groups. In EGFR CNG Pts OS was improved with G compared to P (HR=0.53 95%CI 0.28, 0.98 p=0.042), with survival for G vs P 71 vs 64% ,38 vs 14% , 25 vs 5% and 13 vs 0% at 3 ,6, 9, and 12 months respectively. There was no difference in OS for G vs P in EGFR No CNG pts (HR=0.892 95%CI 0.69, 1.16 p=0.395). For PFS EGFR CNG pts, HR=0.58, 95%CI 0.30, 1.07 p=0.080 for G vs P and HR=0.83 95% CI 0.64, 1.07,p=0.144 for EGFR No CNG pts. DCR was improved for G in EGFR CNG pts(42 vs 13%, p=0.035), and less so for EGFR No CNG (24 vs 14 %, p=0.053). EGFR amplification(6%) pts gained greatest benefit from G ( OS, HR=0.19 95%CI 0.05, 0.65 p=0.007). Conclusions: EGFR CNG identified a subgroup of EC who benefit from Gefitinib as a second line treatment and is a useful predictive biomarker for the first stratified treatment approach in this setting and also a subgroup that may be responsive to other anti-EGFR therapies. Clinical trial information: ISRCTN32435732.
Biodegradable Metals for Cardiovascular Stents: from Clinical Concerns to Recent Zn‐Alloys
Authors: Patrick K. Bowen, Emily R. Shearier, Shan Zhao, Roger J. Guillory, Feng Zhao, Jeremy Goldman, Jaroslaw W. Drelich
Journal: Advanced Healthcare Materials (2016)

Metallic stents are used to promote revascularization and maintain patency of plaqued or damaged arteries following balloon angioplasty. To mitigate the long‐term side effects associated with corrosion‐resistant stents (i.e., chronic inflammation and late stage thrombosis), a new generation of so‐called “bioabsorbable” stents is currently being developed. The bioabsorbable coronary stents will corrode and be absorbed by the artery after completing their task as vascular scaffolding. Research spanning the last two decades has focused on biodegradable polymeric, iron‐based, and magnesium‐based stent materials. The inherent mechanical and surface properties of metals make them more attractive stent material candidates than their polymeric counterparts. A third class of metallic bioabsorbable materials that are based on zinc has been introduced in the last few years. This new zinc‐based class of materials demonstrates the potential for an absorbable metallic stent with the mechanical and biodegradation characteristics required for optimal stent performance. This review compares bioabsorbable materials and summarizes progress towards bioabsorbable stents. It emphasizes the current understanding of physiological and biological benefits of zinc and its biocompatibility. Finally, the review provides an outlook on challenges in designing zinc‐based stents of optimal mechanical properties and biodegradation rate.
Case 2-1992
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, D.S. Sax, J.-P. Vonsattel
Journal: New England Journal of Medicine (1992)

Presentation of CaseAn 88-year-old woman was seen at this hospital because of a question of Huntington's disease.The patient was well until 28 years earlier, around the time that her husband had a stroke, when she became less interested in her usual activities and spent much time staring out a window. Approximately five years later she began to make restless movements, characterized by repeated lifting of her heels off the ground and by turning her feet from side to side. When the patient was 69 years old, a physician who cared for her and two of her sisters noted . . .
Deficiency of Hepatic Organic Anion-Binding Protein, Impaired Organic Anion Uptake by Liver and Physiologic Jaundice in Newborn Monkeys
Authors: A. Jonathan Levi, Zenaida Gatmaitan, Irwin M. Arias
Journal: New England Journal of Medicine (1970)

The possibility that "physiologic" jaundice in monkeys results from immaturity of the hepatic organic anion-uptake process was investigated by serial measurement of the initial plasma clearance of intravenously administered bromsulfalein (BSP), the serum bilirubin concentration and the hepatic intracellular concentration of Y and Z, two cytoplasmic organic anion-binding proteins. The intracellular concentration of Y, plasma clearance of BSP and serum bilirubin concentrations were abnormal in newborn monkeys and reached mature values within the first 10 days of life. These findings suggest that relative deficiency of Y, the main acceptor protein, may be important in the etiology of "physiologic jaundice" in monkeys as well as other primates, including man.
Clonal Chromosomal Abnormalities Showing Multiple-Cell-Lineage Involvement in Acute Myeloid Leukemia
Authors: Mauri Keinänen, James D. Griffin, Clara D. Bloomfield, Joy Machnicki, Albert de la Chapelle
Journal: New England Journal of Medicine (1988)

To determine whether one or more hematopoietic-cell lineages are involved in acute myeloid leukemia (AML), we designed a technique that simultaneously identifies a cell as malignant and determines its lineage. We used numerical clonal chromosomal abnormalities, which are readily detected, to indicate neoplasia, and monoclonal antibodies in an alkaline phosphatase–antialkaline phosphatase detection procedure to identify lineages as granulocytic–monocytic, erythrocytic, or megakaryocytic. Examination of bone marrow from 12 patients with AML showed metaphases of granulocytic-monocytic lineage with abnormal karyotypes in all patients. In seven patients, we also detected abnormal karyotypes in the erythrocytic or megakaryocytic lineage. In all four patients with monosomy 7, both granulocytic-monocytic and erythrocytic cells were affected. Two of four patients with trisomy 8 also had evidence of multiple-lineage involvement, but in two the erythrocytic lineage had normal karyotypes, suggesting an origin at a progenitor-cell stage committed to granulocytic–monocytic development. Multiple-lineage involvement was found in AML both arising de novo (four of five analyzable cases) and following another cancer (three of four analyzable cases). These data demonstrate multiple-lineage involvement in a high proportion of cases of AML and suggest that many cases originate from the multipotent hematopoietic cell or from an earlier progenitor cell. (N Engl J Med 1988; 318:1153–8.)
Cost analysis of non-medical vs. treatment-related costs in patients with chemotherapy for colorectal cancer
Authors: S. G. Hahn, G. Jacobs, H. Heck, S. Kremers, H. Brase, B. Jüngling, S. Zeuzem, A. Matzdorff, M. P. Lutz
Journal: Journal of Clinical Oncology (2008)

6619 Background: There is an ongoing debate about the cost-effectiveness of chemotherapy in colorectal cancer which is entirely based on direct medical cost evaluation and thus reflects mainly the view of health-care providers. In contrast, other costs which have to be covered by the patient and by society, e.g. loss of income or household productivity, support by relatives, transportation etc, are unknown. We hypothesized that these costs are as high as the direct medical costs. Methods: Patients with ongoing systemic palliative or adjuvant chemotherapy for colorectal cancer were asked to complete a structured questionnaire (cost diary) with all cancer-related resource use during a 4-week period in a prospective manner. Outpatients able to comply were included from five oncological centers. Direct treatment-related non-medical costs were differentiated from indirect costs (i.e. productivity loss) in a standardized manner according to the german AG Reha- Ökonomie. Direct medical costs were obtained from health care providers and verified using the public accounting system. Results: 76 pts were evaluated, 68 agreed to participate. 63 diaries have been completed. The mean age was 65 years. The average non-medical costs were $2.864 per patient and month with no significant differences between palliative (n=45, $3.016) or adjuvant (n=18, $2.477) treatment. Of these, direct non-medical costs were $1485 (range $18 - $7.178) per patient and month with 43% due to care by relatives, 49% to loss of leisure time and 5% to transportation. Indirect costs were $1.379 for all patients with a range from $0 in patients without employment to $4.825 for those patients who had to interrupt work (n=18). The median direct treatment costs per patient were $7.156 (range $290 - $13.909). In summary, the overall medical and non-medical costs were $10.020/month, of whom 71% were directly related to medical treatment. 15% were non health-care related but treatment-associated costs, whereas 14% were indirect costs. Conclusions: The costs of colorectal cancer treatment in germany are largely dominated by direct health-care related costs. As compared to other chronic diseases, the non-medical costs are relatively low because the majority of patients are above 65 years old and thus are retired. No significant financial relationships to disclose.
A Controlled Trial of Immunotherapy in Insect Hypersensitivity
Authors: Kevin J. Hunt, Martin D. Valentine, Anne K. Sobotka, Allen W. Benton, Frank J. Amodio, Lawrence M. Lichtenstein
Journal: New England Journal of Medicine (1978)

Insect hypersensitivity is currently treated by immunization using whole-body extracts. We compared this regimen with immunotherapy using insect venoms or placebo in groups of 20 patients matched for history and sensitivity, as judged by venom skin test, histamine release and IgE antibody to venom. After six to 10 weeks of immunization, systemic reactions to stings occurred in seven of 12, seven of 11, and one of 18 patients treated with placebo, whole-body extract, and venom, respectively. Placebo and whole-body extract gave similar results and were significantly less effective than venom immunotherapy (P less than 0.01). The 14 patients with failure of treatment with whole-body extract and placebo were subsequently provided with venom immunotherapy; one reacted to a subsequent sting. We conclude that venom immunotherapy is clinically superior to therapy on whole-body extract or placebo.
Combined Therapy With BRD4 Antagonist and JAK Inhibitor Is Synergistically Lethal Against Human Myeloproliferative Neoplasm (MPN) Cells
Authors: John A Valenta, Warren Fiskus, Taghi Manshouri, Sunil Sharma, Jun Qi, Leasha J Schaub, Bhavin Shah, Melissa Rodriguez, Santhana Devaraj, Swaminathan Padmanabhan Iyer, Srdan Verstovsek, James E Bradner, Kapil N. Bhalla
Journal: Blood (2013)
P276 The Prevalence of Ticarcillin Hyper-susceptible Pseudmonoas aeruginosa isolates from Non Cystic Fibrosis Bronchiectasis patients compared to patients with Cystic Fibrosis and controls
Authors: IT Hettiarachchi, T O’Sullivan, M Wootton, J Duckers, R Dhillon
Journal: Thorax (2015)

<h3>Background and aims</h3> Pseudomonas aeruginosa (PsA) is associated with considerable morbidity and mortality in Non-Cystic Fibrosis bronchiectasis (NCFB) and Cystic Fibrosis (CF) patients. Ticarcillin, a carboxypenicillin, is occasionally used in NCFB and CF to treat pulmonary exacerbations. In CF, a subpopulation of PsA exists that is hypersusceptible to ticarcillin (Tichs) <i>in vitro</i>, (minimum inhibitory concerntration [MIC] &lt;4 µg/ml). This phenotype, is associated with reduced MICs to β-lactams, fluoroquinolones, tetracyclines and a degree of resistance to aminoglycosides. The aim of this study was to investigate whether this Tichs strain exists in NCFB patients and compare this to the prevalence rates from CF and control cohorts. We also assessed whether this strain correlated with enhanced susceptibility to temocillin and other anti-pseudomonal antibiotics. <h3>Methods</h3> 18 isolates of PsA from NCFB patients, 23 PsA isolates from CF patients and 18 PsA isolates from controls with no chronic lung disease were analysed. MICs for each isolate were determined by agar dilution using ISO20776–1 for the antibiotics listed in Table 1 and interpreted using EUCAST breakpoints. <h3>Results</h3> The NCFB isolates had the highest prevalence of the Tichs strain of the three cohorts we tested, with a prevalence of 76%, compared to a prevalence of 48% in the CF cohort and 0% in the controls. Resistant strains of PsA were more prevalent in the CF cohort compared to the NCFB and control cohorts, except for temocillin and ticarcillin where the CF and NCFB cohorts had lower MICs compared to the control cohort (Table 1). The Tichs strain in NCFB and CF was associated with reduced MICs to all antibiotics apart from ciprofloxacin in comparison to the non- Tichs strain. In CF, the Tichs strain was also associated with increased MICs to gentamicin. <h3>Conclusion</h3> Our data supports the existence of a Tichs strain of PsA in NCFB patients, which existed in greater prevalence compared to our CF cohort. This appears to correlate with reduced MICs to temocillin, to which PsA would normally be resistant. Therefore, temocillin may provide a useful alternative to the current anti-pseudomonal antibiotics in treating NCFB and CF patients.
Abstract 19300: Drug Screening in Human Neutral Lipid Storage Disease iPSCells Identifies Modulators of Intracellular Lipid Metabolism That Reduce Disease Phenotype in vitro
Authors: Rajarajan Kuppusamy, Becca Feistritzer, Marc Engels, Anthony Sturzu, Karolina Plonowska, Guang Li, Arun Sharma, Kenta Nakamura, Hinson John, Xiaojing Huang, Wenpo Chuang, Ken-ichi Hirano, Sean Wu
Journal: Circulation (2014)

Induced pluripotent stem cells (iPSCs) hold great promise as in vitro disease models for pathway discovery and therapeutic drug screening. Here, we generated an in vitro model of neutral lipid storage disease, myopathy subtype (NLSD-M), a condition characterized by a marked elevation of lipid accumulation in cardiac and skeletal muscle due to the loss of functional adipose triglyceride lipase (ATGL), by reprogramming patient fibroblasts into iPSCs. These hiPSCs were confirmed of carrying mutations in exon 5and exon 7 of the ATGL gene and were shown to recapitulate the disease phenotype by the presence of Oil Red O positive lipid granules in cardiomyocytes. To corroborate this finding, expression of metabolic genes such as Peroxisome proliferator-activated receptors (PPAR-a and PPAR-g) were significantly decreased in diseased cardiomyocytes compared to control. Furthermore, the down-regulation of PPAR-gamma coactivators (PGC-1a and PGC-1b) and PPAR target genes expression were associated with increased lipid accumulation in vitro. Utilizing the previously identified compounds that induces glycolysis and suppresses oxidative respiration, we found that the accumulation of intracellular lipids in cardiomyocytes was reduced in treated cells when compared with un-treated cells (0.041 ± 0.02 vs 0.186 ± 0.05). Strikingly, such a treatment effect was not observed when Wild Type iPSC derived cardiomyocytes was studied instead, suggesting a disease-specific effect of the identified drugs. Our results represent one of the first successful human induced Pluripotent Stem Cell validation of high throughput drug screening hits from murine iPSC lines. Given the increased prevalence of NLSD-Min the Japanese population, our findings raise the prospect that a treatment for this devastating disease using drug hits from in vitro iPSC screening may be feasible in the near future.
Tamoxifen, a Trigger Factor of Hereditary Angioedema with Normal C1-INH with a Specific Mutation in the F12 Gene (HAE-FXII)
Authors: Stephan Rietz, Konrad Bork, Karin Wulff, Guenther Witzke, Jochen Hardt
Journal: Journal of Allergy and Clinical Immunology (2016)
Treating Patients with Severe Sepsis
Authors: Arthur P. Wheeler, Gordon R. Bernard
Journal: New England Journal of Medicine (1999)

Sepsis is an infection-induced syndrome defined as the presence of two or more of the following features of systemic inflammation: fever or hypothermia, leukocytosis or leukopenia, tachycardia, and tachypnea or a supranormal minute ventilation.1 When an organ system begins to fail because of sepsis, the sepsis is considered severe. Each year, sepsis develops in more than 500,000 patients in the United States, and only 55 to 65 percent survive.2,3 Fortunately, the death rates in some subgroups of patients with sepsis-induced organ failure have decreased, even though there is no specific therapy for sepsis.3,4 The reduced mortality may be . . .