tbuckley/cabot-search huggingface dataset:
Abstract 3406: Activity of catechol-O-methyltransferase gene promoter polymorphisms in renal cancer cells
Authors: Inik Chang, Shinichiro Fukuhara, Darryn K. Wong, Ankurpreet Gill, Varahram Shahryari, Soichiro Yamamura, Shahana Majid, Sharanjot Saini, Hiroshi Hirata, Koji Ueno, Guoren Deng, Rajvir Dahiya, Yuichiro Tanaka
Journal: Cancer Research (2014)

Abstract Catechol-compounds such as 4-hydroxy-estrogen have been shown to play a role in the renal carcinogenesis process. To counter the effects of the highly reactive and mutagenic catechol-estrogens, the catechol-O-methyltransferase (COMT) gene detoxifies these compounds by forming methoxy compounds, which have been shown to be biologically inactive. Proper COMT function is thus vital for cells and a mechanism by which activity levels can be affected is through polymorphisms. The Val(158)Met polymorphism that correlates with renal cancer has been shown to reduce COMT enzymatic activity, but also of importance are those variants in the promoter region which can lead to alterations in gene expression levels. The aim of this study was to determine if polymorphisms of the COMT promoter can influence their transcription levels. To examine this, plasmids containing wildtype regions of the COMT promoter were obtained and site-directed mutagenesis used to create polymorphic variants. Constructs were then transfected into the Caki-1 renal cell line to measure their effects on gene expression by using a luciferase reporter assay. A total of 8 polymorphic sites covering the distal and proximal promoter region were evaluated. Results indicate that the variant at polymorphic sites rs2020917 (C to T), rs13306278 (C to T), and rs6269 (A to G) caused a significant reduction (P&amp;lt;0.01) whereas rs165656 (G to C) and rs165722 (C to T) caused a significant increase (P&amp;lt;0.01) in luciferase activity. No differences were observed for rs737865 (A to G), 4646312 (T to C), and rs3810595 (G to C). These results demonstrate polymorphisms of the COMT promoter region to cause altered expression levels in renal cells and warrant further studies with clinical case-control specimens to determine their associations for renal cell cancer. Citation Format: Inik Chang, Shinichiro Fukuhara, Darryn K. Wong, Ankurpreet Gill, Varahram Shahryari, Soichiro Yamamura, Shahana Majid, Sharanjot Saini, Hiroshi Hirata, Koji Ueno, Guoren Deng, Rajvir Dahiya, Yuichiro Tanaka. Activity of catechol-O-methyltransferase gene promoter polymorphisms in renal 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 3406. doi:10.1158/1538-7445.AM2014-3406
Maintenance of the inotropic effect of digoxin on long-term treatment.
Authors: B E Griffiths, W J Penny, M J Lewis, A H Henderson
Journal: BMJ (1982)

M-mode echocardiograms and systolic time intervals were recorded before and six weeks after stopping digoxin in 11 patients in sinus rhythm to see whether the inotropic effect of digoxin was maintained with long-term treatment. Significant changes indicating a reduction in inotropic state on stopping digoxin were observed in the group. Clinical deterioration occurred in only one patient, associated with evidence of initially impaired cardiac function rather than an atypical response to digoxin. This study provides evidence that chronic digoxin treatment does continue to exert a positive inotropic effect.
Multiple Single-breath Measurements of Nitric Oxide in the Intubated Patient
Authors: Daniel C. Törnberg, Håkan Björne, Jon O. Lundberg, Eddie Weitzberg
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Multiple flow rate measurements of exhaled nitric oxide (NO) have been advocated to fractionate NO from alveolar and bronchial sources. The aim of this study was to develop a method by which multiple single-breath exhalations at various flow rates could be performed in intubated, mechanically ventilated patients. Nine patients without lung disease were studied awake and after intubation, during general anesthesia. A suction ejection system connected to a restrictor valve was used to control the exhalation flow rate. From these measurements the fraction of alveolar NO (FANO), the fraction of airway wall NO (FawNO), and the airway wall transfer rate (DNO) were calculated. The fraction of exhaled NO was reduced by 50% after intubation. DNO was also reduced by intubation (from 10 ± 1.3 to 6.4 ± 2.1 nl second−1 ppb−1 × 10−3) whereas neither FawNO nor FANO was affected. The peak NO concentration after 20 seconds of apnea during general anesthesia was similar to calculated FawNO. The vacuum aspiration method used in this study allowed for reproducible multiple single-breath measurements and calculation of alveolar and bronchial NO parameters. Further studies will reveal whether this methodology will improve the value of exhaled NO analysis in intubated, mechanically ventilated patients with pulmonary disease.
Acquired amegakaryocytic thrombocytopenic purpura
Authors: Neeraj Agarwal, Joseph E. Spahr, Theresa L. Werner, David L. Newton, George M. Rodgers
Journal: American Journal of Hematology (2006)

Acquired amegakaryocytic thrombocytopenia is an unusual hematologic disorder characterized by thrombocytopenia in association with markedly diminished bone marrow megakaryocytes. We report a case that responded to treatment with cyclosporine but not to IL-11. The bone marrow biopsy, repeated after resolution of thrombocytopenia, showed normal number of megakaryocytes.
URIC ACID AND HEMOGLOBIN LEVEL: NOVEL RISK PREDICTORS OF ACUTE KIDNEY INJURY IN PATIENT UNDERGOING PERCUTANEOUS CORONARY INTERVENTION WITH DRUG-ELUTING STENTS
Authors: SangHo Park, Seung-Woon Rha, Seung-Jin Lee, Won-Yong Shin, Dong-Kyu Jin, Ji Young Park, Byoung Geol Choi, Kanhaiya L. Poddar, Meera Kumari, Yun Kyung Kim, Cheol Ung Choi, Hong Euy Lim, Jin Won Kim, Chang Gyu Park, Hong Seog Seo, Dong Joo Oh
Journal: Journal of the American College of Cardiology (2011)
THE USE OF NATIONAL FOODS IN TREATING DIABETIC PATIENTS OF FOREIGN BIRTH
Authors: FRANCES STERN
Journal: JAMA (1927)

The use of food in the body is now fairly well understood, and the composition of all familiar food material is known. The cold, hard, mathematical basis for dietetics has therefore been laid, but the ability to calculate and balance rations is not enough for the successful physician. He should remind himself occasionally of the counsel set forth by a well known authority:1Much of the feeding in the treatment of disease must rest on clinical experience, for the personal equation always enters into the picture, and it will always be true that certain individuals will not react to food stimuli in a normal way, idiosyncrasy playing a not inconsiderable role. Since this is true in health, how much greater the variation in disease when one considers that all people differ in their habits, environment, age, activity of gland and susceptibility to certain food elements.  A consideration of the
Ethical Responsibility of Phase 0 Trials
Authors: Roberto Jun Arai, Paulo Marcelo Gehm Hoff, Gilberto de Castro, Arnold Stern
Journal: Clinical Cancer Research (2009)

To the Editor: We read with great interest the article by Abdoler et al. (1) on the ethics-based interpretation of phase 0 trials in cancer patients. In our opinion, drugs that consistently show favorable toxicity profile and beneficial therapeutic activity in preclinical models should be tested in anima nobile. This is particularly important for molecular targeted therapies, in which impressive responses are sometimes seen in particular subpopulations.As pointed out by the authors, the reconceptualization of the investigator-subject relationship and a deep evaluation of the subjects' understanding of phase 0 trials are essential for subject enrollment. Paying modest quantities was also recommended. This must be seriously considered especially in the developing countries where most participants are in a vulnerable condition due to lower per capita incomes (2, 3).Whereas recruitment of terminally ill cancer patients in phase 0 trials is controversial, the issues of indirect and/or direct benefits such as access to therapy once successful are also equally disputed. Paragraph 30 of Declaration of Helsinki and its clarification note emphasize the needed assurance of post-trial access by study participants to the best therapeutic method identified as beneficial during the drug development. This is particularly important for subjects enrolled in phase III trials. However, because cancer patients that are eligible to phase 0 trials are end-staged, their chances of direct clinical benefits from proven therapy are highly limited. In this context, the nontherapeutic nature of such trials will always raise ethical and/or moral-based discussions (4). Therefore, access to identified beneficial therapy should be expanded to subjects enrolled in earlier trials on which phase III were based.Paragraph 19 of the Declaration of Helsinki states that medical research is ethically justified only if there is a reasonable chance that the population on which it is conducted will benefit from the results. It is expected that subsequent trials using information derived from phase 0 would lead to fewer toxicities and higher probability of clinical benefits. Therefore, the community or population from which the subjects are derived may benefit from data originated in phase 0 trials, if the emphasis of subsequent trials is placed to the same tested population. Importantly, by extending the access of subsequent trials where phase 0 was conducted, the population, and not only the tested individuals per se, may benefit from the proven therapy.No potential conflicts of interest were disclosed.
Hemoglobinopathies Affect Hemoglobin A_1C Measurement
Authors: Gregory S. Holt
Journal: Annals of Internal Medicine (1991)

Letters1 July 1991Hemoglobinopathies Affect Hemoglobin A1C MeasurementGregory S. Holt, MD, James L. Wofford, MD, Ramon Velez, MDGregory S. Holt, MDSearch for more papers by this author, James L. Wofford, MDSearch for more papers by this author, Ramon Velez, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-115-1-68_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editors:Assays for hemoglobin (Hgb) A1Care considered by some to be the "gold standard" for monitoring long-term glycemic control in diabetic patients (1). Various techniques are currently available to measure Hgb A1C, including chromatography (column ion-exchange, liquid, affinity, minicolumn), electrophoresis (isoelectric focusing), and colorimetric methods. These methods have been shown to have reasonable precision. However, ion-exchange chromatography, a popular and relatively inexpensive technique, seems to be affected by hemoglobin variants (2). A falsely elevated Hgb A1Cby this method may occur in patients with increased Hgb F or beta-thalassemia, whereas falsely low results may occur when Hgb...References1. StrowigRaskin SP. Insulin treatment and patient management. In: Rifkin H, Porte D, eds. Diabetes Mellitus: Theory and Practice. 2d edition. New York: Elsevier; 1990:514-23. Google Scholar2. Eberentz-LhommeDucrocqIntratorElionNunezAssain CRSJER. Haemoglobinopathies: a pitfall in the assessment of glycosylated hemoglobin by ion-exchange chromatography. Diabetologia. 1984;27:596-8. CrossrefMedlineGoogle Scholar3. Beutler E. The sickle diseases and related disorders. In: Williams W, Beutler E, eds. Hematology. 4th edition. New York: McGraw-Hill; 1990:613-44. Google Scholar4. Ravel R. Tests for diabetes and hypoglycemia. In: Ravel R, ed. Clinical Laboratory Medicine. 5th edition. Chicago: Year Book Medical Publishers, Inc.; 1989:471-3. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Bowman-Gray School of Medicine Reynolds Health Center Winston-Salem, NC 27103 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByEffect of Hemoglobinopathies on Hemoglobin A1c MeasurementsFetal Hemoglobin Alters Hemoglobin A1c MeasurementsRichard W. Bergstrom, MD, James R. Kelley, MD, W. Kenneth Ward, MD 1 July 1991Volume 115, Issue 1Page: 68-69KeywordsBeta-thalassemiaChromatographyHemoglobinHemoglobinopathies Issue Published: 1 July 1991 PDF DownloadLoading ...
Mutant forms of spectrin alpha-subunits in hereditary elliptocytosis.
Authors: S L Marchesi, J T Letsinger, D W Speicher, V T Marchesi, P Agre, B Hyun, G Gulati
Journal: Journal of Clinical Investigation (1987)

Two variant spectrins have been described in hereditary elliptocytosis (HE) and pyropoikilocytosis (HPP). Both are characterized by increased susceptibility of the alpha I (N-terminal) 80-kD domain to mild tryptic digestion, yielding peptides of 46-50 or 65-68 kD (T50a and T68 in our terminology). In this report we add a third unstable spectrin alpha I domain found in three kindreds with HE; alpha IT80 in this type of spectrin is cleaved by mild tryptic digestion to a 50-kD peptide (T50b) distinguished from T50a by its more basic isoelectric point. All three spectrins show impaired self-association to form oligomers. Intermediate tryptic peptides of the three unstable alpha I domains from HE spectrins were characterized by monoclonal immunoblotting and I125 limit peptide mapping and affinity purified using polyclonal anti-alpha IT80. Partial amino acid sequences of alpha I domain peptides were obtained from two unrelated patients for each of the three variant spectrins. T50a results from cleavage at arginine 250 or lysine 252 of alpha IT80; a proline replaced the normal leucine or serine at residues 254 and 255, respectively. T50b and a 19-kD peptide result from cleavage at arginine 462 or arginine 464; a proline replaced the normal residue 465 (in T19b) in one of the two patients studied. T68 results from cleavage at arginine 131. In both 68-kD peptides examined, a leucine is inserted at residue 150. The relationship of the sequence changes to the new tryptic cleavages, to the current model of alpha I domain structure, and to defective spectrin self-association is discussed.
Evaluation of combination therapy against hepatitis C virus infection in human liver chimeric mice
Authors: Ype P. de Jong, Charles M. Rice, Alexander Ploss
Journal: Journal of Hepatology (2010)

Hepatitis C virus (HCV) is a blood–borne pathogen that chronically infects approximately 130 million people worldwide and can lead to liver cirrhosis and hepatocellular carcinoma. HCV is divided in seven major genotypes, of which genotype 1 causes the majority of infections in the developed world. In contrast to several other chronic viral infections, e.g. human immunodeficiency virus (HIV) and hepatitis B virus (HBV), HCV can be eradicated in a subset of individuals who clear acute infection and in patients that achieve a sustained virologic response (SVR) after treatment. Cure of HCV decreases the risk of end-stage liver disease and/or hepatocellular carcinoma, even in patients who are cirrhotic. It is, therefore, generally recommended that chronically infected individuals undergo treatment if they are expected to tolerate the current medications. For more than a decade, treatment for all HCV genotypes has been based on a combination of interferon-a (IFNa) and ribavirin (RBV), with the main variables being duration of treatment, the formulation of IFNa, and the dosage of RBV. This combination has empirically proven efficacious but its mechanisms of action remain elusive. IFNa is believed to have both direct antiviral, as well as host immunostimulatory effects, and a wide array of mechanisms have been proposed for RBV, from increased viral mutagenesis to helper T cell modulation [6]. Even with optimal treatment duration, formulation and dosing, however, less than half of genotype 1/4 and approximately two thirds of genotype 2/3 infected patients achieve SVR [7]. Meanwhile, both drugs result in significant adverse events in the majority of patients, most notably cytopenias that frequently require growth factor administration, flu like symptoms, and neuropsychiatric side effects. It is for these reasons that new drugs are currently under development. HCV is a positive stranded RNA virus that encodes a single polyprotein, which is cleaved by host and viral proteases into its functional structural and non-structural (NS) subunits. Two of the viral gene products, namely the NS3-4A protease and NS5B polymerase, have proven attractive drug targets. Over the
Midlife vascular risk factors and Alzheimer's disease in later life: longitudinal, population based study
Authors: M. Kivipelto
Journal: BMJ (2001)

<h3>Abstract</h3> <b>Objective:</b> To examine the relation of midlife raised blood pressure and serum cholesterol concentrations to Alzheimer9s disease in later life. <b>Design:</b> Prospective, population based study. <b>Setting:</b> Populations of Kuopio and Joensuu, eastern Finland. <b>Participants:</b> Participants were derived from random, population based samples previously studied in a survey carried out in 1972, 1977, 1982, or 1987. After an average of 21 years9 follow up, a total of 1449 (73%) participants aged 65–79 took part in the re-examination in 1998. <b>Main outcome measures:</b> Midlife blood pressure and cholesterol concentrations and development of Alzheimer9s disease in later life. <b>Results:</b> People with raised systolic blood pressure (≥160 mm Hg) or high serum cholesterol concentration (≥6.5 mmol/l) in midlife had a significantly higher risk of Alzheimer9s disease in later life, even after adjustment for age, body mass index, education, vascular events, smoking status, and alcohol consumption, than those with normal systolic blood pressure (odds ratio 2.3, 95% confidence interval 1.0 to 5.5) or serum cholesterol (odds ratio 2.1, 1.0 to 4.4). Participants with both of these risk factors in midlife had a significantly higher risk of developing Alzheimer9s disease than those with either of the risk factors alone (odds ratio 3.5, 1.6 to 7.9). Diastolic blood pressure in midlife had no significant effect on the risk of Alzheimer9s disease. <b>Conclusion:</b> Raised systolic blood pressure and high serum cholesterol concentration, and in particular the combination of these risks, in midlife increase the risk of Alzheimer9s disease in later life. <h3>What is already known on this topic</h3> Vascular risk factors may play an important part as risk factors for Alzheimer9s disease No population based studies have evaluated prospectively the impact of both midlife blood pressure and cholesterol concentration in both men and women on the subsequent development of Alzheimer9s disease <h3>What this study adds</h3> Raised systolic blood pressure and high serum cholesterol concentration, and in particular the combination of these risks, in midlife increased the risk of Alzheimer9s disease in later life Raised systolic blood pressure and hypercholesterolaemia may have a role in the pathogenesis of Alzheimer9s disease; more emphasis should be placed on identification and appropriate treatment of these conditions
The Cardiac Output in Chronic Cor Pulmonale
Authors: NOBLE O. FOWLER, RICHARD N. WESTCOTT, RALPH C. SCOTT, EMILY HESS
Journal: Circulation (1952)

A comparative study was made of the resting cardiac index in 12 cases of chronic cor pulmonale, in 14 normal subjects, and in 10 patients suffering from heart failure due to vascular or valvular disease. The mean cardiac index in the subjects with chronic cor pulmonale was significantly higher than in the group with other types of heart disease and was significantly lower than in the normal individuals. An explanation for the failure to observe elevation of cardiac output in some of these cases of chronic cor pulmonale is offered.
Targeting EGFRs and Src signaling with a modified ectodomain of human EGFR (EBIP) and dasatinib in breast cancer.
Authors: J Nautiyal, Y Yu, BB Patel, AP Majumdar
Journal: Cancer Research (2009)

Abstract Abstract #3069 It is becoming increasingly evident that many solid tumors including breast cancer show increased activation of several growth factor receptors, specifically EGFR and its family members (EGFRs) as well as c-Src, a non-receptor tyrosine kinase that promote proliferation, inhibit apoptosis and induce metastasis. The EGF-receptor (EGFR) consists of an extracellular ligand-binding domain, a hydrophobic transmembrane region, and an intracellular tyrosine kinase domain. The extracellular or ectodomain of EGFR is essential for ligand-binding and subsequent homo/heterodimerization of the receptor. This raises the possibility that the ectodomain of EGFR could be utilized to inhibit EGFR functions and in turn cellular growth. Recently, we generated an ectodomain of human EGFR (hEGFR), composed of 1-448 amino acids fragment of hEGFR and the 30 amino acid epitope (known as “U” region) of rat EGFR-Related Protein (ERRP) fused at the carboxy-terminal end. The new protein, referred to as EBIP (ErbB Inhibitory Protein), as has been observed for ERRP (Xu et al. Mol. Cancer Ther. 2005 (4): 435-42), inhibits growth of colon and breast cancer cells that express varying levels of EGFR and/or its family members. We hypothesize that inhibition of c-Src and EGFRs will be an effective therapeutic strategy for breast cancer. To test our hypothesis we used Dasatinib (BMS-354825; Bristol-Myers Squibb), a newly developed highly potent, ATP-competitive Src and Abl kinase inhibitor and ErbB Inhibitory Protein (EBIP). Four different breast cancer cell lines (MDA-MB-468, SKBr-3, MDA-MB-453 and MDA-MB-231) expressing different levels of EGFR and/or its family members were used. Both EBIP and dasatinib caused a dose dependent inhibition of growth in all breast cancer cells, but dasatinib was less effective compared to EBIP. However, the combination of Dasatinib and EBIP synergistically inhibited cell growth. In EGFR overexpressing MDA-MB-468 cells, the combination therapy also inhibited invasion through extracellular matrix and decreased colony formation. Induction of apoptosis could be attributed to activation of caspases -9 and -8 and by modulating phosphorylation of anti- and pro-apoptotic proteins, Bcl-2 and Bad, respectively. The combination of Dasatinib and EBIP produced a greater inhibition of EGFR and Src activation and their downstream signaling pathways involving Akt and p44/42 MAPK. Additionally, we observed that EGFR promoter activities as well as transactivation of NFκB in MDA-MB-468 cells were greatly reduced. In conclusion, our data suggest that combination treatment of Dasatinib and EBIP that target EGFRs and Src could be a highly effective therapy for breast cancer than mono therapy, as they are likely to impact several aspects of tumor progression. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3069.
EEG ABNORMALITIES AS A CORRELATE OF BEHAVIOR IN ADOLESCENT MALE DELINQUENTS
Authors: S. DALE LOOMIS
Journal: American Journal of Psychiatry (1965)

The incidence of abnormal EEGs among 150 adolescent male delinquents confined in a correctional institution was studied, and an attempt was made to correlate the abnormal tracings with deviant delinquent behavior. Little such correlation was evident, and no increased incidence of EEG abnormality was noted. It is suggested that an undue emphasis has been placed on the role of such pathology in general delinquent behavior. The increased evidence of EEG abnormality among a group specifically referred for EEG indicated that it is apparently possible to select such cases on the basis of aberrant clinical behavior or unusual history. The specifics of such selection remain vague, however, and would seem to warrant further investigation. The psychiatric evaluation in an institutional setting was noted to be a significant area for the further elaboration and clarification of these findings.