tbuckley/cabot-search huggingface dataset:
Variation in the Intergenic Spacer of Ribosomal DNA of Wild Wheat, Triticum dicoccoides. In Israel
Authors: RB Flavell, M O'Dell, P Sharp, E Nevo, A Beiles
Journal: Molecular Biology and Evolution (1986)

The variation in the intergenic spacer of ribosomal DNA (rDNA) of tetraploid wild emmer wheat, Triticum dicoccoides, in Israel was examined in 112 individual plants representing 12 populations tested earlier for allozymic variation encoded by 50 gene loci. The variation detected by means of restriction endonucleases results in part from variation in the number of 135-bp repeats that are in tandem array in the intergenic DNA. Intergenic spacers of genes within a single locus are relatively homogeneous, but populations of T. dicoccoides display a wide spectrum of rDNA spacer-length variation. Some populations are very homogeneous, whereas others are heterogeneous. The most homogeneous population consists of plants with spacerrDNA lengths that are the most common in T. dicoccoides in Israel. The lengths of specific regions within the spacer DNA are identical for loci on different chromosomes in the most homogeneous population. The allozymic and rDNA diversities within populations are highly and significantly intercorrelated, and both allozymic and rDNA diversities are significantly correlated with and predictable in terms of climatic variables.
X-linked Inhibitor of Apoptosis: A Chemoresistance Factor or a Hollow Promise
Authors: Hamid Kashkar
Journal: Clinical Cancer Research (2010)

The X-linked inhibitor of apoptosis (XIAP) is the only cellular protein that has evolved to potently inhibit the enzymatic activity of mammalian caspases and promotes resistance to apoptosis. Given its role in apoptosis and its frequently elevated expression in malignant cells, XIAP has garnered the most attention as a promising therapeutic target in cancer to overcome drug resistance. Accordingly, XIAP is thought to render tumor cells resistant to chemotherapy through its ability to inhibit caspases, and it is on this basis that XIAP has been proposed as an important adverse biomarker for chemoresistance in cancer patients. Here, the current understanding of the role of XIAP in cancer is reviewed. Further, the notion is explored that the elevated XIAP expression frequently observed in malignant tissues is, at least, not exclusively responsible for the resistance of tumor cells to conventional therapeutic treatment; rather, the function of XIAP seems to be conducive to the process of malignant transformation and/or progression.
Audit of acute admissions of COPD: standards of care and management in the hospital setting
Authors: C.M. Roberts, I. Ryland, D. Lowe, Y. Kelly, C.E. Bucknall, M.G. Pearson
Journal: European Respiratory Journal (2001)

Despite publication of several management guidelines for COPD, relatively little is known about standards of care in clinical practice. Data were collected on the management of 1400 cases of acute admission with Chronic Obstructive Pulmonary Disease in 38 UK hospitals to compare clinical practice against the recommended British Thoracic Society standards. Variation in the process of care between the different centres was analysed and a comparison of the management by respiratory specialists and nonrespiratory specialists made. There were large variations between centres for many of the variables studied. A forced expiratory volume in one second measurement was found in only 53% of cases. Of the investigations recommended in the acute management arterial blood gases were performed in 79% (interhospital range 40–100%) of admissions and oxygen was formally prescribed in only 64% (range 9–94%). Of those cases with acidosis and hypercapnia 35% had no further blood gas analysis and only 13% received ventilatory support. Long-term management was also deficient with 246 cases known to be severely hypoxic on admission yet two-thirds had no confirmation that oxygen levels had returned to levels above the requirements for long-term oxygen therapy. Only 30% of current smokers had cessation advice documented. To conclude, the median standards of care observed fell below those recommended by the guidelines. The lowest levels of performance were for patients not under the respiratory specialists, but specialists also have room for improvement. The substantial variation in the process of care between hospitals is strong evidence that it is possible for other centres with poorer performance to improve their levels of care.
In vivo detection of Staphylococcus aureus endocarditis by targeting pathogen-specific prothrombin activation
Authors: Peter Panizzi, Matthias Nahrendorf, Jose-Luiz Figueiredo, Jennifer Panizzi, Brett Marinelli, Yoshiko Iwamoto, Edmund Keliher, Ashoka A Maddur, Peter Waterman, Heather K Kroh, Florian Leuschner, Elena Aikawa, Filip K Swirski, Mikael J Pittet, Tilman M Hackeng, Pablo Fuentes-Prior, Olaf Schneewind, Paul E Bock, Ralph Weissleder
Journal: Nature Medicine (2011)
Efficient Analysis of Experimental Observations
Authors: W J Dixon
Journal: The Annual Review of Pharmacology and Toxicology (1980)

The prime goal of this chapter is to encourage researchers in pharmacology to make use of some of the statistical techniques developed in recent years that could increase the efficiency of their analyses. The topics we have chosen to illustrate are fractional replicates of fac­ torial experiments, single degrees of freedom and half-normal plots in the analysis of variance, robust estimation, and up-and-down method for quan­ tal responses. Briefly, the advantages of the techniques illustrated here are the follow­ ing.
Ornithine Aminotransferase versus GABA Aminotransferase: Implications for the Design of New Anticancer Drugs
Authors: Hyunbeom Lee, Jose I. Juncosa, Richard B. Silverman
Journal: Medicinal Research Reviews (2014)

Ornithine aminotransferase (OAT) and γ-aminobutyric acid aminotransferase (GABA-AT) are classified under the same evolutionary subgroup and share a large portion of structural, functional, and mechanistic features. Therefore, it is not surprising that many molecules that bind to GABA-AT also bind well to OAT. Unlike GABA-AT, OAT had not been viewed as a potential therapeutic target until recently; consequently, the number of therapeutically viable molecules that target OAT is very limited. In this review the two enzymes are compared with respect to their active-site structures, catalytic and inactivation mechanisms, and selective inhibitors. Insight is offered that could aid in the design and development of new selective inhibitors of OAT for the treatment of cancer.
Early B-Cell Differentiation in Merkel Cell Carcinomas: Clues to Cellular Ancestry
Authors: Axel zur Hausen, Dorit Rennspiess, Veronique Winnepenninckx, Ernst-Jan Speel, Anna Kordelia Kurz
Journal: Cancer Research (2013)

Merkel cell carcinoma (MCC) is a highly malignant neuroendocrine nonmelanoma skin cancer, which is associated with the Merkel cell polyoma virus (MCPyV). Recently, expression of the terminal deoxynucleotidyl transferase (TdT) and the paired box gene 5 (PAX 5) has been consistently reported in the majority of MCCs. We tested 21 MCCs for the expression of MCPyV, TdT, PAX5, IgG, IgM, IgA, kappa, and lambda by immunohistochemistry and assessed IgH and Igk rearrangement in all 21 MCCs. All of the MCCs revealed specific expression of PAX5 and 72.8% of the MCCs expressed TdT. In addition, most of the MCCs revealed specific expression of one or more Ig subclasses and kappa or lambda. One MCC did reveal monoclonal IgH and Igk rearrangement next to two other MCCs showing Igk rearrangement. As coexpression of TdT and PAX5 under physiologic circumstances is restricted to pro/pre- and pre-B cells we propose, on the basis of our results, that the cell of origin of MCCs is a pro/pre- or pre-B cell rather than the postmitotic Merkel cells. MCPyV infection and transformation of pro-/pre-B cells are likely to induce the expression of simple cytokeratins as has been shown for SV40 in other nonepithelial cells. This model of cellular ancestry of MCCs might impact therapy and possibly helps to understand why approximately 20% of MCCs are MCPyV-negative.
Different types of chronic hepatitis in alcoholic patients: Does chronic hepatitis induced by alcohol exist?
Authors: Shujiro Takase, Nobuo Takada, Nobuyuki Enomoto, Minoru Yasuhara, Aicira Takada
Journal: Hepatology (1991)

To verify the existence of chronic hepatitis induced by alcohol, the clinicopathological features of chronic hepatitis in heavy drinkers were studied using various viral markers. Histological features of chronic active hepatitis were seen in 27 heavy drinkers. These patients were divided into four groups. The AL group (seven cases) consisted of alcoholics who were negative for both hepatitis C antibody and HBsAg; the HB group (four cases) was positive for HBsAg; the HC1 group (seven cases) was positive for hepatitis C antibody but negative for hepatitis C virus-RNA genome; and the HC2 group (nine cases) was positive both for hepatitis C antibody and hepatitis C virus-RNA genome. Serum AST and ALT activity declined during 4 wk of abstinence in most patients in the AL group and in the HC1 group. The response of serum AST and ALT to abstinence was poor in most patients in the HB group and the HC2 group. Serum desialo-transferrin and alcohol liver membrane antibodies were detected more frequently in the sera of patients in the AL group and HC1 group. A trend toward increased frequency of centrilobular ballooning existed in the AL group, but this did not reach statistical significance. These results suggest that chronic active hepatitis in patients in the AL group, in whom markers of HBV and hepatitis C virus were absent, may be caused by alcohol. Patients in the HC1 group who had hepatitis C antibody but not hepatitis C virus-RNA may represent cases where both alcohol and hepatitis C virus are involved.
Receptor-mediated entry of beta-glucuronidase into the parasitophorous vacuoles of macrophages infected with Leishmania mexicana amazonensis.
Authors: V L Shepherd, P D Stahl, P Bernd, M Rabinovitch
Journal: The Journal of Experimental Medicine (1983)

125I-labeled rat preputial gland beta-glucuronidase was shown by light and electron microscopic radioautography to accumulate within the parasitophorous vacuoles of in vitro derived bone marrow macrophages infected with Leishmania mexicana amazonensis. beta-glucuronidase uptake was mediated by the mannose receptor, since the penetration of the ligand was inhibited by mannan. Uptake was detected as soon as 4 h after incubation of infected cells with the ligand, and increased at 24 and 48 h. The label persisted in the vacuoles for at least 24 h after a 24-h pulse with the ligand, a finding compatible with the relatively long half-life of labeled beta-glucuronidase in normal macrophages. Parasitophorous vacuoles were also labeled in macrophages exposed to the ligand only before infection, indicating that secondary lysosomes containing the ligand fused with the parasitophorous vacuoles. Another mannosylated ligand, mannose-BSA, which, in contrast to beta-glucuronidase, is rapidly degraded in macrophage lysosomes, did not detectably accumulate in the vacuoles. The results support and extend information previously obtained with electron opaque tracers that emphasizes the phagolysosomal nature of Leishmania parasitophorous vacuoles. In addition, the results suggest that appropriate mannosylated molecules may be used as carriers for targeting of leishmanicidal drugs to the parasitophorous vacuoles of infected macrophages.
Diagnosis of psychiatric disorder in clinical evaluation of chronic fatigue syndrome
Authors: Alicia Deale, Simon Wessely
Journal: Journal of the Royal Society of Medicine (2000)

The overlap of symptoms in chronic fatigue syndrome (CFS) and psychiatric disorders such as depression can complicate diagnosis. Patients often complain that they are wrongly given a psychiatric label. We compared psychiatric diagnoses made by general practitioners and hospital doctors with diagnoses established according to research diagnostic criteria. 68 CFS patients referred to a hospital fatigue clinic were assessed, and psychiatric diagnoses were established by use of a standardized interview schedule designed to provide current and lifetime diagnoses. These were compared with psychiatric diagnoses previously given to patients. Of the 31 patients who had previously received a psychiatric diagnosis 21 (68%) had been misdiagnosed: in most cases there was no evidence of any past or current psychiatric disorder. Of the 37 patients who had not previously received a psychiatric diagnosis 13 (35%) had a treatable psychiatric disorder in addition to CFS. These findings highlight the difficulties of routine clinical evaluation of psychiatric disorder in CFS patients. We advise doctors to focus on subtle features that discriminate between disorders and to use a brief screening instrument such as the Hospital Anxiety and Depression Scale.
A Trial of a 7-Valent Pneumococcal Conjugate Vaccine in HIV-Infected Adults
Authors: Neil French, Stephen B. Gordon, Thandie Mwalukomo, Sarah A. White, Gershom Mwafulirwa, Herbert Longwe, Martin Mwaiponya, Eduard E. Zijlstra, Malcolm E. Molyneux, Charles F. Gilks
Journal: New England Journal of Medicine (2010)

is a leading and serious coinfection in adults with human immunodeficiency virus (HIV) infection, particularly in Africa. Prevention of this disease by vaccination with the current 23-valent polysaccharide vaccine is suboptimal. Protein conjugate vaccines offer a further option for protection, but data on their clinical efficacy in adults are needed.
Hand Hygiene among Physicians: Performance, Beliefs, and Perceptions
Authors: Didier Pittet, Anne Simon, Stéphane Hugonnet, Carmen Lúcia Pessoa-Silva, Valérie Sauvan, Thomas V. Perneger
Journal: Annals of Internal Medicine (2004)

Background: Physician adherence to hand hygiene remains low in most hospitals. Objectives: To identify risk factors for nonadherence and assess beliefs and perceptions associated with hand hygiene among physicians. Design: Cross-sectional survey of physician practices, beliefs, and attitudes toward hand hygiene. Setting: Large university hospital. Participants: 163 physicians. Measurements: Individual observation of physician hand hygiene practices during routine patient care with documentation of relevant risk factors; self-report questionnaire to measure beliefs and perceptions. Logistic regression identified variables independently associated with adherence. Results: Adherence averaged 57% and varied markedly across medical specialties. In multivariate analysis, adherence was associated with the awareness of being observed, the belief of being a role model for other colleagues, a positive attitude toward hand hygiene after patient contact, and easy access to hand-rub solution. Conversely, high workload, activities associated with a high risk for cross-transmission, and certain technical medical specialties (surgery, anesthesiology, emergency medicine, and intensive care medicine) were risk factors for nonadherence. Limitations: Direct observation of physicians may have influenced both adherence to hand hygiene and responses to the self-report questionnaire. Generalizability of study results requires additional testing in other health care settings and physician populations. Conclusion: Physician adherence to hand hygiene is associated with work and system constraints, as well as knowledge and cognitive factors. At the individual level, strengthening a positive attitude toward hand hygiene and reinforcing the conviction that each individual can influence the group behavior may improve adherence among physicians. Physicians who work in technical specialties should also be targeted for improvement.
High-Purity Isolation and Recovery of Circulating Tumor Cells using Conducting Polymer-deposited Microfluidic Device
Authors: SeungHyun Jeon, WooYoung Hong, Eun Sook Lee, Youngnam Cho
Journal: Theranostics (2014)

We have developed a conductive nano-roughened microfluidic device and demonstrated its use as an electrically modulated capture and release system for studying rare circulating tumor cells (CTCs).The microchannel surfaces were covalently decorated with epithelial cancer-specific anti-EpCAM antibody by electrochemical deposition of biotin-doped polypyrrole (Ppy), followed by the assembly of streptavidin and biotinylated antibody.Our method utilizes the unique topographical features and excellent electrical activity of Ppy for i) surface-induced preferential recognition and release of CTCs, and ii) selective elimination of non-specifically immobilized white blood cells (WBCs), which are capable of high-purity isolation of CTCs.In addition, the direct incorporation of biotin molecules offers good flexibility, because it allows the modification of channel surfaces with diverse antibodies, in addition to anti-EpCAM, for enhanced detection of multiple types of CTCs.By engineering a series of electrical, chemical, and topographical cues, this simple yet efficient device provides a significant advantage to CTC detection technology as compared with other conventional methods.
VORAPAXAR REDUCES PERIPHERAL REVASCULARIZATION REGARDLESS OF THE NUMBER OF DISEASED TERRITORIES: INSIGHTS FROM THE TRA2P–TIMI 50 TRIAL
Authors: Marc Bonaca, Mark Creager, Jeffrey Olin, Benjamin Scirica, Erin Bohula, Sabina Murphy, Eugene Braunwald, David Morrow
Journal: Journal of the American College of Cardiology (2013)
How Physicians Use Laboratory Tests
Authors: Wiveka E. Elion-Gerritzen
Journal: JAMA (1978)

<h3>To the Editor.—</h3> Having conducted a study<sup>1</sup>similar to the one Laurence P. Skendzel, MD, describes in "How Physicians Use Laboratory Tests" (239:1077, 1978), I can underline his finding that physicians react widely different to laboratory test results. This diversity in attitude has been described before<sup>2-4</sup>(201:519, 1967). West,<sup>3</sup>for example, concludes: "Under certain common circumstances some diabetologists would classify as normal more than half of the one- and two-hour (glucose) values considered to be abnormal by other well-qualified diabetologists." My comment on Dr Skendzel's article relates to the experimental setup of his study. He presented a series of brief clinical problems to specialists in internal medicine. In each case an initial laboratory result for a certain constituent was given. Clinicians were asked to indicate which subsequent value in the same patient would be compatible with a medically important change. The initial values were all purposely selected
Rombo syndrome: A second case report and review
Authors: Robin Ashinoff, Mark Jacobson, Donald V. Belsito
Journal: Journal of the American Academy of Dermatology (1993)

Rombo syndrome is inherited as an autosomal dominant trait.Patients have a grainy appearance to the skin, multiple basal cell carcinomas, trichoepitheliomas, hypotrichosis, and a peculiar cyanosis of the hands and feet.We report the second case ofthis syndrome. CASE REPORTA 92-year-old white woman had multiple lesions on her face.The patient had mild dementia; her only medication was a phenothiazine.She was otherwise well.The patient and the patient's family were poor historians, although they reported no one else in the family with any skin problems.There was no history of x-irradiation.Physical examination revealed ulcerated pearly papules and plaques on the patient's left cheek, left side of the neck, right cheek, and right side of her upper lip.In ad-
Galactose-1-phosphate uridyltransferase and galactokinase activity in cultured human diploid fibroblasts and peripheral blood leukocytes
Authors: Thomas A. Tedesco, William J. Mellman
Journal: Journal of Clinical Investigation (1969)

The specific activities of galactokinase and galactose-1-phosphate uridyltransferase were determined in peripheral blood leukocytes directly after separation from whole blood, and in cultured skin fibroblasts at various times during the subculture growth period. Growth curves were obtained for fibroblasts based on three different parameters: direct cell counts, total protein, and total deoxyribonucleic acid (DNA) content. At the time in culture when the specific activity of both enzymes was maximal and least variable, the ratio of transferase to galactokinase correlated well with the transferase genotypes of the original tissue donors. Leukocyte transferase: galactokinase ratios gave a similar distribution pattern. Whereas transferase activity in both fibroblasts and leukocytes was similar, galactokinase was approximately three times as active in fibroblasts as in leukocytes. All fibrobast cell strains tested had similar galactokinase activity regardless of transferase genotype.The kinetic properties of fibroblast galactokinase were examined. Galactose-1-phosphate inhibits galactokinase activity in both normal and galactosemic cell strains, whereas other glycolytic intermediates have no effect. There was no detectable transferase activity in eight galactosemic (Gt(G)/Gt(G)) cell strains when transferase activity was maximal in cell strains of other transferase genotypes. Inhibitors responsible for the absence of transferase activity could not be demonstrated. In addition, transferase activity in galactosemic cell lysates was not observed in cells during logarithmic growth; measurable uridine diphosphate galactose (UDPgal) pyrophosphorylase activity was found in human diploid fibroblast cultures, as well as significant levels of endogenous uridine triphosphate (UTP) in lysates of fibroblast cultures.
Single Center Experience of a New Intensive Induction Therapy for Ewing’s Family of Tumors: Feasibility, Toxicity, and Stem Cell Mobilization Properties
Authors: S.J. Strauss, A. McTiernan, D. Driver, M. Hall-Craggs, A. Sandison, A.M. Cassoni, A. Kilby, M. Michelagnoli, J. Pringle, J. Cobb, T. Briggs, S. Cannon, J. Witt, J.S. Whelan
Journal: Journal of Clinical Oncology (2003)

To examine the feasibility, tolerability, and toxicity of an intensified induction regimen (vincristine, ifosfamide, doxorubicin, and etoposide [VIDE]) in patients with newly diagnosed Ewing's family of tumors (EFT); to assess ability to maintain dose-intensity, and predictability of peripheral-blood stem cell mobilization.Thirty patients were treated with vincristine 1.4 mg/m2 (maximum 2 mg) on day 1, doxorubicin 20 mg/m2, ifosfamide 3 g/m2 plus mesna and etoposide 150 mg/m2 on days 1 to 3. Cycles were given every 21 days for up to six cycles.One-hundred and seventy cycles of VIDE were given. The median treatment interval was 21 days (21 to 42) and nadir count: hemoglobin 8.3 (6.3 to 11.9), neutrophils 0.045 (0.0 to 2.1), and platelets 45 (3 to 343). There were 96 episodes of infection requiring hospitalization (56%). Growth factor support reduced infectious complications by 34%. Etoposide dose was reduced, or omitted, in 24% of cycles. Four patients did not complete six cycles due to unacceptable toxicity and one patient progressed on treatment. Twenty patients underwent peripheral-blood stem cell harvesting, 15 after cycle 3, and five after cycle 4. Median CD34+ yield was 4.6 x 106/kg per patient (1.8 to 14.5). Overall response to treatment, measured in 24 patients, was 88%. Seven of 11 patients undergoing surgery achieved greater than 90% necrosis of tumor (64%).VIDE is an effective induction regimen with substantial but acceptable toxicity that allows predictable mobilization of stem cells. Maintenance of dose-intensity is feasible in the majority of patients. Growth factors play a role in maintaining dose-intensity and reduce infectious complications.