tbuckley/cabot-search huggingface dataset:
Inactivation of S-adenosylhomocysteine hydrolase during adenine arabinoside therapy.
Authors: S L Sacks, T C Merigan, J Kaminska, I H Fox
Journal: Journal of Clinical Investigation (1982)

To assess for possible inhibition of cellular transmethylation during adenine arabinoside (ara-A) therapy, S-adenosylhomocysteine hydrolase activity was analyzed in 10 patients with chronic hepatitis B virus infection. In six patients receiving ara-A, enzyme activity was suppressed to 0-2% of control erythrocyte enzyme activity. This decrease in enzyme activity was evident within 4 h of starting the drug infusion and continued for 7 d after cessation of therapy. S-adenosylhomocysteine hydrolase activity of peripheral mononuclear cells was also measured in two patients receiving ara-A. Suppression to as low as 3.5% of pretreatment levels was found; however, marked fluctuations with partial return of enzyme activity during therapy was also observed in mononuclear cells. Inhibition of an enzyme involved in transmethylation reactions was observed in patients during ara-A therapy. This could contribute to the side effects and antiviral properties of ara-A.
Gaps in anaphylaxis management at the level of physicians, patients, and the community: a systematic review of the literature
Authors: M. Kastner, L. Harada, S. Waserman
Journal: Allergy (2009)

Diagnosis and management of anaphylaxis can be a challenge because reactions are often unexpected and progress quickly. The focus of anaphylaxis management has mostly been on the acute episode, with little attention given to the long-term management of patients at risk. This is compounded by conflicting information in current guidelines and a general lack of agreement among clinicians about which management strategies are the most appropriate. We systematically reviewed the literature to identify and summarize studies that investigated gaps in anaphylaxis management. Our search included MEDLINE, EMBASE, CINAHL, and Evidence-Based Medicine Reviews. Studies were included if they addressed an outcome describing gaps in anaphylaxis knowledge, education, anaphylaxis management, and quality of life (QOL). Populations of interest were health care professionals involved in the care of patients at risk for anaphylaxis, and patients of any age, their parents, caregivers, and teachers in primary care, hospital or community settings. Of 5014 citations that were identified, the final 59 studies (selected from 75 full-text articles) met the inclusion criteria. Two hundred and two gaps were identified and classified according to major themes: gaps in knowledge and anaphylaxis management (physicians and patients); gaps in follow-up care (physicians); and QOL of patients and caregivers. Findings from this systematic review revealed gaps in anaphylaxis management at the level of physicians, patients, and the community. Findings will be used to provide a basis for developing interventional strategies to help address these deficiencies.
Regulation and revalidation of doctors: Summary of other responses
Authors: Birte Twisselmann
Journal: BMJ (2006)

Pringle's editorial on revalidation, which was largely supportive of the chief medical officer's report, came in for unbridled criticism.1 Eleven respondents, mostly general practitioners from the United Kingdom, warned against introducing fundamental new measures in such haste, expressing serious concerns about abolishing self regulation and about the safety of patients.

Adam Pringle sets the tone in criticising the hurry: “Anybody pretending to intellectual validity and scientific rigour would test and validate their tools first, and design their system later.” He also takes issue with the proposed enforced membership …
Dithranol-UV-A phototherapy (DUVA) for psoriasis: a treatment without dressings
Authors: C. HINDSON, B. DIFFEY, FRANCES LAWLOR, ANNE DOWNEY
Journal: British Journal of Dermatology (1983)

Dithranol in yellow soft paraffin with 2% salicylic acid was applied daily (increasing concentrations from 0.2% to 5%) for 1 hour to twenty consecutive patients with diffuse psoriasis. The ointment was then washed off and patients were irradiated with 10 J cm-2 of UV-A radiation since the absorption spectrum of dithranol is maximum in the UV-A waveband. The median clearance time was 14 days (range 7-39 days). No dressings were required. The patients were allowed to apply an emollient if the skin became dry.
Treatment of Dysmenorrhea-Reply
Authors: Penny Wise Budoff
Journal: JAMA (1982)

In Reply.—  My comments were specifically addressed to the treatment of primary dysmenorrhea and stated that the benefits of the NSAI drugs were too quickly dismissed if by chance the first prescribed drug did not work for that particular patient. Based on six years' experience with thousands of women, I suggested that a change to a different NSAI is most often all that is required.  Obviously, not all NSAIs are equivalent to each other, although overall they often give clinically similar results. The fact that they can differ clinically is borne out by the finding that patients with primary dysmenorrhea may respond to one drug and not another and that failure on one treatment may often be corrected by changing to another drug of the same type. These same therapy problems are known to occur in other disorders, ie, inflammatory joint disease, but they are poorly understood.  Chemical idiosyncrasy concerns
Geographic Variations of the International Diabetes Federation and the National Cholesterol Education Program–Adult Treatment Panel III Definitions of the Metabolic Syndrome in Nondiabetic Subjects
Authors: Carlos Lorenzo, Manuel Serrano-Ríos, María T. Martínez-Larrad, José L. González-Sánchez, Segundo Seclén, Arturo Villena, Clicerio Gonzalez-Villalpando, Ken Williams, Steven M. Haffner
Journal: Diabetes Care (2006)

OBJECTIVE—We have carried out international comparisons of the metabolic syndrome using the International Diabetes Federation (IDF) and National Cholesterol Education Program–Adult Treatment Panel III (ATP III) definitions. This analysis could help to discern the applicability of these definitions across populations. RESEARCH DESIGN AND METHODS—Nondiabetic subjects aged 35–64 years were eligible for analysis in population-based studies from San Antonio (Mexican Americans and non-Hispanic whites, n = 2,473), Mexico City (n = 1,990), Spain (n = 2,540), and Peru (n = 346). κ Statistics examined the agreement between metabolic syndrome definitions. RESULTS—Because of the lower cutoff points for elevated waist circumference, the IDF definition of the metabolic syndrome generated greater prevalence estimates than the ATP III definition. Prevalence difference between definitions was more significant in Mexican-origin and Peruvian men than in Europid men from San Antonio and Spain because the IDF definition required ethnic group–specific cutoff points for elevated waist circumference. ATP III and IDF definitions disagreed in the classification of 13–29% of men and 3–7% of women. In men, agreement between these definitions was 0.54 in Peru, 0.43 in Mexico City, 0.62 in San Antonio Mexican Americans, 0.69 in San Antonio non-Hispanic whites, and 0.64 in Spain. In women, agreement between definitions was 0.87, 0.89, 0.86, 0.87, and 0.93, respectively. CONCLUSIONS—The IDF definition of the metabolic syndrome generates greater prevalence estimates than the ATP III definition. Agreement between ATP III and IDF definitions was lower for men than for women in all populations and was relatively poor in men from Mexico City.
Resolution of psoriasis following allogeneic bone marrow transplantation for chronic myelogenous leukemia: Case report and review of the literature
Authors: Heiwa Kanamori, Masatsugu Tanaka, Hiroshi Kawaguchi, Satoshi Yamaji, Katsumichi Fujimaki, Naoto Tomita, Shin Fujisawa, Yoshiaki Ishigatsubo
Journal: American Journal of Hematology (2002)

Abstract We describe a case of a 49‐year‐old man with chronic myelogenous leukemia (CML) whose coincidental psoriasis resolved following allogeneic bone marrow transplantation (BMT). The patient had suffered from psoriasis for 20 years and was treated with corticosteroid ointment. He was diagnosed as having CML in 1998, and his psoriasis deteriorated following interferon therapy. In March 1999, he received a BMT from an HLA‐identical sister after undergoing a conditioning regimen involving busulfan, cytosine arabinoside, and cyclophosphamide. Prophylaxis of acute graft‐versus‐host disease was done using short‐term methotrexate and cyclosporin A. His psoriasis improved immediately and disappeared completely on day 70 after BMT. For 2.5 years, his CML remains in remission and he is free of psoriasis without undergoing immunosuppressive therapy. This case suggests the potential benefits of the treatment of immune‐mediated diseases with allogeneic BMT. Am. J. Hematol. 71:41–44, 2002. © 2002 Wiley‐Liss, Inc.
Reversal of Early Graft Rejection After Renal Heterotransplantation in Man
Authors: Keith Reemtsma, Brian H. McCracken, Jorgen U. Schlegel, Maurice A. Pearl, Charles W. De Witt, Oscar Creech
Journal: JAMA (1964)

A 43-year-old man in terminal uremia received a renal transplant from a chimpanzee. The grafted kidneys began functioning immediately but four days later threatened rejection occurred. This was reversed following increased doses of immunosuppressive drugs and radiotherapy. A milder episode of threatened rejection occurring in the fourth week was also reversed. Tests demonstrated function of both transplanted kidneys without evidence of function of the patient's own kidneys. As the patient entered his sixth post-transplantation week he was ambulatory, eating an unrestricted diet, had normal urinary volume and content, and normal blood urea nitrogen and serum creatinine levels. Two months following the heterotransplantation, the patient died with pneumonia. The transplanted kidneys showed no evidence of rejection.
Pressure gradient related to energy conversion in the aorta.
Authors: J Melbin, A Noordergraaf
Journal: Circulation Research (1983)

In this study, we analyzed a common form of experimental investigation of blood vessels, in which measurements are obtained with branches ligated. Utilizing representative pressure and flow pulses and the full expression for the equation of motion, we calculated the axial pressure gradient, in the time domain at a plane in the descending aorta. The time function representing the ratio between axial pressure gradient and axial flow for the resulting tapering geometry was subjected to Fourier analysis. The harmonics were utilized to obtain the real and imaginary components of the longitudinal impedance as if it were a linear system. In a linear system, the real and imaginary components represent the viscous and inertial properties of the fluid, respectively. For the system studied, however, the real part contained both viscous and substantial in-phase components arising from the inertial terms of the equation of motion. The real part, therefore, cannot be interpreted as indicative solely of dissipated energy. When measurements are obtained from an adulterated system, caution must be exercised if the interpretation is to be considered that of the real system. The analysis clarifies an anomalous issue concerning resistive features of the aorta.
Renal Angiotensinase Activity
Authors: HAROLD D. ITSKOVITZ, LEONARD D. MILLER
Journal: Circulation Research (1966)

A rat bioassay technique was employed to determine the localization and properties of the angiotensinase activity present in kidney homogenates of anesthetized rats. The angiotensinase activity per gram of renal cortex was four times greater than renal papilla or medulla. The complete destruction of proximal renal tubular cells by mercuric chloride resulted in losses of cortical angiotensinase activity averaging 40% of control values. The destruction of cells of both the proximal and distal renal tubules by sodium potassium tartrate caused a 90% reduction in angiotensinase activity. Marked reductions in cortical angiotensinase activity were measured in rats injected with meralluride 2 hours previously. The addition of meralluride to in vitro systems of normal rat kidney homogenates caused similar depressions of angiotensinase activity. The presence of reduced glutathione in the reaction media interfered with the ability of meralluride to inhibit angiotensinase and enhanced the activity of this enzyme to greater than normal levels in the absence of the mercurial. Ammonium ion in a concentration of.18 m inhibited angiotensinase activity of renal cortical homogenates by a moderate degree. When both meralluride and ammonium were present in the homogenate system their effects to depress angiotensinase appeared additive.
Long-term Follow-up of Hexamethylene Diisocyanate-, Diphenylmethane Diisocyanate-, and Toluene Diisocyanate-induced Asthma
Authors: PÄIVI L. PIIRILÄ, HENRIK NORDMAN, HELENA M. KESKINEN, RITVA LUUKKONEN, SUVI-PÄIVIKKI SALO, TIMO O. TUOMI, MATTI TUPPURAINEN
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

In 1976–1992 245 new cases of asthma induced by diisocyanates were diagnosed, caused by hexamethylene diisocyanate (HDI) in 39%, diphenylmethane diisocyanate (MDI) in 39%, and toluene diisocyanate (TDI) in 17% of the cases. Our aim was to study the clinical outcome of diisocyanate-induced asthma. A questionnaire was sent to the 235 patients alive in 1995, and validated by reexamining clinically 91 of them. The study was carried out on average 10 (3-19) yr after the diagnosis. Of the patients 82% experienced symptoms of asthma, 34% used no medication, and 35% were on regular medication. The patients having displayed immunoglobulin E (IgE) antibodies to isocyanates used less medication (OR 0.273; CI 0.098, 0.758) and had fewer symptoms of asthma (OR 0.329; CI 0.124, 0.875) than the IgE-negative ones. They also had a significantly shorter duration of symptoms (p = 0.0025), latency period (p = 0.0249), and duration of exposure (p = 0.0008) than the IgE-negative patients. This did not, however, entirely explain the more favourable outcome of the IgE-positive patients. Patients with HDI-induced asthma used less medication (OR 0.412; CI 0.229, 0.739) than patients with MDI- and TDI-induced asthma. The results confirm the generally rather poor medical outcome of diisocyanate-induced asthma; the persistence of symptoms and unspecific bronchial reactivity were pronounced in TDI-induced asthma. A more favourable outcome was associated with IgE mediation and HDI inducement.
Abstract 2201: Pathway analysis of breast cancer genome wide association study highlights three pathways and one canonical signaling cascade
Authors: Idan Menashe, Dennis Maeder, Montserrat Garcia-Closas, Jonine D. Figueroa, Samsiddhi Bhattacharjee, Melissa Rotunno, Peter Kraft, David J. Hunter, Stephen J. Chanock, Philip S. Rosenberg, Nilanjan Chatterjee
Journal: Cancer Research (2010)

Abstract Genome-wide association studies (GWAS) focus on relatively few highly significant loci while less attention is given to other genotyped markers. Employing pathway analysis to existing GWAS data may shed light on relevant biological processes, and illuminate new candidate genes. We employed a pathway-based approach to the breast cancer GWAS data of the National Cancer Institute (NCI) Cancer Genetic Markers of Susceptibility (CGEMS) project that includes 1145 cases and 1142 controls. Pathways were retrieved from three databases: KEGG, BioCarta, and the NCI's Protein Interaction Database (PID). Genes were represented by their most strongly associated SNP, and an enrichment score (ES) reflecting the overrepresentation of gene-based association signals in each pathway was calculated using a weighted Kolmogorov-Smirnov procedure. Finally, hierarchical clustering was used to identify pathways with overlapping genes, and clusters with excess of association signals were determined by the adaptive rank-truncated product (ARTP) method. A total of 421 pathways containing 3962 genes were included in our study. Of these, three pathways (‘Syndecan-1-mediated signaling ‘, ‘Signaling of Hepatocyte Growth Factor Receptor’ and ‘Growth Hormone Signaling’) were highly enriched with association signals (PES &amp;lt; 0.001, False Discovery Rate (FDR) = 0.118). Our clustering analysis revealed that pathways containing key components of the RAS/RAF/MAPK canonical signaling cascade, were significantly more likely to have excess of association signals than expected by chance (PARTP = 0.0051, FDR = 0.07). These results suggest that genetic alterations associated with these three pathways and one canonical signaling cascade may contribute to breast cancer susceptibility. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2201.
Adequacy and utility of the dual-process approach to perception: Time (and research) will tell
Authors: Joel Norman
Journal: Behavioral and Brain Sciences (2002)

My response and reactions to the quite diverse commentaries are presented. Among the topics covered are a response to holders of the ecological viewpoint; memory and learning in the two perceptual systems; development of the two systems; biological motion; size and distance perception; illusion and the two systems; and several others. It is suggested that the dual-process approach is a viable working theory of space perception and, perhaps, of other types of perception as well. Hopefully, future research will enhance it with added refinements and variations on the original theme.
A New IκB Kinase β Inhibitor Prevents Human Breast Cancer Progression through Negative Regulation of Cell Cycle Transition
Authors: Akane Tanaka, Susumu Muto, Masayo Konno, Akiko Itai, Hiroshi Matsuda
Journal: Cancer Research (2006)

Constitutive nuclear factor-kappaB (NF-kappaB) activity plays a crucial role in the development and progression of lymphoma, leukemia, and some epithelial cancers. Given the contribution of NF-kappaB in carcinogenesis, a novel approach that interferes with its activity might have therapeutic potential against cancers that respond poorly to conventional treatments. Here, we have shown that a new IkappaB kinase beta inhibitor, IMD-0354, suppressed the growth of human breast cancer cells, MDA-MB-231, HMC1-8, and MCF-7, by arresting cell cycle and inducing apoptosis. In an electrophoretic mobility shift assay and a reporter assay, IMD-0354 abolished the NF-kappaB activity in MDA-MB-231 cells in a dose-dependent manner. In the cells incubated with IMD-0354, cell cycle arrested at the G0-G1 phase and apoptotic cells were increased. The expression of some cell cycle regulatory molecules and antiapoptotic molecules was suppressed in cells treated with IMD-0354. On the other hand, cyclin-dependent kinase suppressor p27Kip1 was up-regulated by the addition of IMD-0354. Daily administration of IMD-0354 inhibited tumor expansion in immunodeficient mice into which MDA-MB-231 cells were transplanted. These results indicate that NF-kappaB may contribute to cell proliferation through up-regulation of cell cycle progression; accordingly, inhibition of NF-kappaB activity might have a therapeutic ability in the treatment of human breast cancers.
Abstract 2479: Bz-423: A novel benzodiazephine mitochondrial-targeted drug, cytotoxic to human ovarian cancer cells.
Authors: Gong He, Lijun Tan, Weimin Wang, Anthony E. Boitano, Natalie A. Vandeven, Anthony W. Opipari, J Rebecca Liu
Journal: Cancer Research (2013)

Abstract Objectives: Bz-423 is a chemically synthesized 1,4-benzodiazepine with cytotoxic activity in several cell types. We sought to determine the anti-neoplastic potential and mechanism of action in human ovarian cancer cells. Methods: A total of 12 human ovarian cancer cell lines were used. Cultured cells were treated with Bz-423 or vehicle control in dose-response and time-course experiments. Viability was determined on the basis of plasma membrane integrity using flow cytometry. The mechanism leading to death in these cells was characterized ultrastructurally using electron micrscopy and by determining changes in reaction oxygen species, glutathione, mitochondrial function, caspase and Bak activation. Cytochrome c release from mitochondria was analyzed by immunofluorescence. Apoptosome complex formation was monitored by gel filtration chromatography. Results: Bz-423 induced apoptosis in all ovarian cell lines at low micromolar concentrations by generating an intracellular superoxide signal from the mitochondria. The apoptotic response was associated with the release of cytochrome c from the mitochondria, collapse of the mitochondrial transmembrane gradient, and formation of the apoptosome complex containing Apaf-1 and caspase-9. The release of cytochrome c and a decrease in mitochondria glutathione within 2 hours of treatment was identified by ultrastructural evidence of mitochondrial swelling. Furthermore, Bak activation was necessary for apoptosis. Bz-423 effectively induced apoptosis in chemoresistant ovarian cancer cells overexpressing Bcl-2 and Bcl-xL. Conclusion: Bz-423 is a novel compound that effectively kills human ovarian cancer cells, including cells that are resistant to conventional chemotherapies such as Cisplatinum. This compound has cytotoxic qualities that are unique among benzodiazepines. The mechanism of action involves both proximal and direct effects on the cell mitochondria that lead to apoptosis. Bz-423 is a novel compound that may have broad clinical impact in the treatment of ovarian cancer patients. Citation Format: Gong He, Lijun Tan, Weimin Wang, Anthony E. Boitano, Natalie A. Vandeven, Anthony W. Opipari, J Rebecca Liu. Bz-423: A novel benzodiazephine mitochondrial-targeted drug, cytotoxic to human ovarian cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2479. doi:10.1158/1538-7445.AM2013-2479 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Review Body Award and Medical Assistants
Authors: I. M. Librach
Journal: BMJ (1975)

woman doctor in question was one of your own editors and the jouTal hierarchy pre- fers iit not to be too widely known that there is now no woman doctor employed at B.M.A.headquarters, though about one-fifth of the profession is composed of women.The B.M.7.dbose to make its only woman doctor redundant in International Women's Year, giving economy as the emouse.One must a4c, was this economy really necessary?Because in 1975 it certainly was not wise.-I am, etc.,
Maternal Mental Health After a Child’s Diagnosis of Autism Spectrum Disorder
Authors: Elizabeth A. Karp, Alice A. Kuo
Journal: JAMA (2015)

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