tbuckley/cabot-search huggingface dataset:
Acetylcholinesterase in the human erythron. II. Biochemical assay
Authors: Ronald D. Barr, Marijke Koekebakker, Alison A. Lawson
Journal: American Journal of Hematology (1988)

Abstract Acetylcholinesterase (AChE) is an integral erythrocyte membrane protein. A role for the enzyme in the developing human erythron is being explored. Assays of AchE by the standard Ellman technique overestimate the amount of enzyme by failing to account for the contribution of hemoglobin to the optical density of the reaction mixture. Furthermore, reliance on substrate selection alone for specificity is unsatisfactory. Incorporation of inhibitors of “true” AchE and of pseudocholinestearase confer greater ability to distinguish one enzyme from the other. In our experience, the inhibitor constant (K 1 ) for edrophonium, which is highly specific for AChE, is approximately 5 × 10 −5 M against adult human erythrocytes that contain significantly more total cholinesterase activity than do erythrocytes from umbilical cord blood. This consists of both “true” and “pseudo” enzyme, the former predominating and accounting for 0.75–1.65 (mean 1.02, median 0.87) femtomoles of substrate hydrolysed per min per cell in adult blood, with values of 0.15–1.04 (mean 0.71, median 0.73) obtained on cord blood. Moreover, the enzyme activity in neonatal erythrocytes has a rather different inhibitor profile from that of adult cells. AChE was also demonstrated in fresh (ALL) and cultured (K562 and HL60) human leukemic cells, as well as in primitive granulocyte‐macrophage and erythroid cells cloned from normal human bone marrow. In the erythroid colonies the enzyme activity was 0–3.76 (mean 1.20, median 0.76) femtomoles per min per cell, apparently the first successful measurement of AChE in such cells.
Abstract 2273: Autophagic cell death induced by curcumin is mediated by p38/Beclin 1 to crosstalk with apoptotic cell death in DU145 cells
Authors: Dongxu Kang, Wungki Park, Joo-Hang Kim, Jae Jin Song
Journal: Cancer Research (2012)

Abstract Curcumin as an anticancer agent was investigated to study how it can regulate cancer cells’ destination to either apoptosis or autophagy. At higher concentration, curcumin induced ROS production leading to JNK and p38 phosphorylation in DU-145 prostate cancer cell. Of the two MAP kinases, p38 was phosphorylated earlier during curcumin treatment, and responsible for curcumin-induced autophagic cell death by using GFP-LC3 expression. p38-induced autophagy signaling pathway occurred at even 1h, and was enhanced by blocking JNK signaling, and JNK signaling was more involved in apoptosis rather than autophagy. In the case of curcumin treatment. Beclin 1, an essential autophagic protein was mainly activated by dissociation from Bcl2 or Bcl-xL after Beclin 1 phosphorylation induced by p38-DAPK, or from Bcl-2 phosphorylation induced by JNK1. Based on these results, we concluded that curcumin exhibited cytotoxicity in DU-145 cells and this cytotoxicity was mediated by p38 signaling pathway triggering both beclin 1 activation to induce autophagic cell death, which in turn inhibits the apoptotic cell death induced by curcumin-ROS-JNK signaling cascade, leading to a complex crosstalk between autophagy and apoptosis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2273. doi:1538-7445.AM2012-2273
Nature group extends rules on disclosure to review authors
Authors: S. Mayor
Journal: BMJ (2003)

The Nature group of journals announced last week that it was extending its policy on disclosure of financial interests to include authors of review papers, in addition to authors of original research papers.

Writing in the October issue of Nature Neuroscience (2003;6: 997), the journals' editors announced that they were widening their policy on financial disclosure after controversy over a review article on mood disorders published last November.

In February Robert Rubin, professor of neurosciences and psychiatry at Drexell University College of Medicine, Allegheny General Hospital, Pittsburgh, and Bernard Carroll, of the Pacific Behavioral Research Foundation, Carmel, California, wrote to the Nature group complaining …
ADENOMATOUS APPENDICULAR POLYPS
Authors: P. C. Martineau
Journal: JAMA (1952)

Adenomatous appendicular polyps are rare. White and Ellis<sup>1</sup>collected a total of 21 cases from the literature in 1945 and added a single case of their own. In 1948 Brewer and Marcus<sup>2</sup>described a patient in whom the polyp had caused an intussusception of the appendix. They were able to gather four other similar cases from older literature, prior to 1923. Numerous workers<sup>3</sup>have suggested that these polyps are precancerous lesions with potentialities similar to those of adenomatous polyps of the colon. Uihlein and McDonald<sup>3c</sup>reported cases studied photomicrographically showing "an adenomatous polyp" containing "regions of malignancy characterized by larger deeper-staining nuclei." They prefer to call tumors with anaplastic areas of that type "papillary adenocarcinoma grade I." In another paper Woodruff and McDonald<sup>4</sup>described a role that adenocarcinoma grade 1 of the appendix may play in the formation of a mucocele and of pseudomyxoma peritonei.
Psychologically Mediated Effects of Diagnostic Tests
Authors: HAROLD C. SOX
Journal: Annals of Internal Medicine (1981)

Laboratory tests are purported to affect patients even if they have no diagnostic value. We tested this hypothesis by measuring clinical outcomes of 176 patients thought clinically to have nonspecific chest pain. They were randomly allocated either to have a routine electrocardiogram and serum creatine phosphokinase test (test group) or to have all diagnostic tests withheld (no-test group). Fewer patients in the test group (20%) reported short-term disability after the index visit than patients in the no-test group (46%) (p = 0.001). Logistic discriminant analysis confirmed that the use of diagnostic tests was an independent predictor of recovery. Patients in the test group felt that care was "better than usual" more often (57%) than patients in the no-test group (31%) (p = 0.001). After the index visit, the two groups were equally worried about serious disease and equally sparing in their use of other medical care for chest pain.
Development of a dual‐color, double fusion FISH assay to detect <i>RPN1/EVI1</i> gene fusion associated with inv(3), t(3;3), and ins(3;3) in patients with myelodysplasia and acute myeloid leukemia
Authors: Brandon M. Shearer, William R. Sukov, Heather C. Flynn, Ryan A. Knudson, Rhett P. Ketterling
Journal: American Journal of Hematology (2010)

Abstract Approximately 2–3% of adult patients with acute myeloid leukemia harbor a rearrangement of RPN1 (at 3q21) and EVI1 (at 3q26.2) as inv(3)(q21q26.2), t(3;3)(q21;q26.2), or ins(3;3)(q26.2;q21q26.2). The most recent World Health Organization (WHO) classification has designated AML with inv(3) or t(3;3) and associated RPN1/EVI1 fusion, as a distinct AML subgroup associated with an unfavorable prognosis. We have created a dual color, double fusion fluorescence in situ hybridization (D‐FISH) assay to detect fusion of the RPN1 and EVI1 genes. A blinded investigation was performed using 30 normal bone marrow samples and 51 bone marrow samples from 17 patients with inv(3)(q21q26.2), 11 patients with t(3;3)(q21;q26.2), and one patient with ins(3;3)(q26.2;q21q26.2) previously defined by chromosome analysis. The unblinded results indicated abnormal RPN1/EVI1 fusion results in 30 (97%) of 31 samples from the inv(3)(q21q26.2) group including seven bone marrow samples for which chromosome analysis was unsuccessful or failed to detect an inv(3)(q21q26.2). Abnormal FISH results were detected in 14 (88%) of 16 samples with t(3;3)(q21;q26.2) and in the sole sample with an ins(3;3)(q26.2;q21q26.2). All 30 negative controls were normal and were used to establish a normal cutoff of 0.6% for the typical abnormal D‐FISH signal pattern. Overall, this D‐FISH assay was more accurate than chromosome analysis and based on the normal cutoff of 0.6%, this assay can be used for minimal residual disease detection and disease monitoring in patients with RPN1/EVI1 fusion. Am. J. Hematol., 2010. © 2010 Wiley‐Liss, Inc.
Scarlet Fever and Necrotizing Fasciitis Caused by Coagulase-Positive Hemolytic Staphylococcus aureus, Phage Type 85
Authors: RICHARD V. MCCLOSKEY
Journal: Annals of Internal Medicine (1973)

The syndromes of scarlet fever and necrotizing fasciitis are typically caused by group A hemolytic streptococci. A 23-year-old woman developed both syndromes. The causative organism was a coagulase-positive hemolytic Staphylococcus aureus, phage type 85. This staphylococcus produced exfoliative toxin in vitro but no delta toxin and only small amounts of alpha toxin. The organism was resistant to penicillin, tetracycline, and neomycin. Filtered broth cultures contained a factor that produced fever and a scarlatiniform rash in a Dick test-positive human volunteer. The staphylococcal erythrogenic toxin may cause the vasculitis of both staphylococcal scarlet fever and necrotizing fasciitis. Initial treatment of adults with suspected bacteremia and either scarlet fever or necrotizing fasciitis should include intravenous administration of a penicillinase-resistant penicillin until the antibiotic sensitivities of the causative organism are known.
Atheromatous Emboli with Progressive Renal Failure
Authors: JOHN T. HARRINGTON
Journal: Annals of Internal Medicine (1968)

Two patients studied by renal arteriography as part of an evaluation for hypertension subsequently developed progressive deterioration of renal function and within 2 to 4 months died in uremia. Atheroembolic disease of the kidney, severe enough to account for the renal failure, was demonstrated by renal biopsy or autopsy. Both patients had severe erosive atheromatous disease of the abdominal aorta and underlying nephrosclerosis with moderate renal insufficiency. The conclusion that the renal arteriography was the critical factor in the initiation of progressive renal failure is based on the temporal relationship between arteriography and the deterioration of renal function, the actual demonstration of embolization during the arteriographic procedure in one of the patients, and the findings of extensive atheroembolism of the kidneys in both. Renal arteriography is an invaluable diagnostic tool, but unless the indications are urgent, it should probably be avoided in patients with extensive arteriosclerosis and impaired renal function. If it is deemed necessary, however, manipulation with rigid catheters should be held to a minimum.
Role for Substance P–Based Nociceptive Signaling in Progenitor Cell Activation and Angiogenesis During Ischemia in Mice and in Human Subjects
Authors: Silvia Amadesi, Carlotta Reni, Rajesh Katare, Marco Meloni, Atsuhiko Oikawa, Antonio P. Beltrami, Elisa Avolio, Daniela Cesselli, Orazio Fortunato, Gaia Spinetti, Raimondo Ascione, Elisa Cangiano, Marco Valgimigli, Stephen P. Hunt, Costanza Emanueli, Paolo Madeddu
Journal: Circulation (2012)

Pain triggers a homeostatic alarm reaction to injury. It remains unknown, however, whether nociceptive signaling activated by ischemia is relevant for progenitor cells (PC) release from bone marrow. To this end, we investigated the role of the neuropeptide substance P (SP) and cognate neurokinin 1 (NK1) nociceptor in PC activation and angiogenesis during ischemia in mice and in human subjects.The mouse bone marrow contains sensory fibers and PC that express SP. Moreover, SP-induced migration provides enrichment for PC that express NK1 and promote reparative angiogenesis after transplantation in a mouse model of limb ischemia. Acute myocardial infarction and limb ischemia increase SP levels in peripheral blood, decrease SP levels in bone marrow, and stimulate the mobilization of NK1-expressing PC, with these effects being abrogated by systemic administration of the opioid receptor agonist morphine. Moreover, bone marrow reconstitution with NK1-knockout cells results in depressed PC mobilization, delayed blood flow recovery, and reduced neovascularization after ischemia. We next asked whether SP is instrumental to PC mobilization and homing in patients with ischemia. Human PC express NK1, and SP-induced migration provides enrichment for proangiogenic PC. Patients with acute myocardial infarction show high circulating levels of SP and NK1-positive cells that coexpress PC antigens, such as CD34, KDR, and CXCR4. Moreover, NK1-expressing PC are abundant in infarcted hearts but not in hearts that developed an infarct after transplantation.Our data highlight the role of SP in reparative neovascularization. Nociceptive signaling may represent a novel target of regenerative medicine.
Complement membrane attack complex stimulates production of reactive oxygen metabolites by cultured rat mesangial cells.
Authors: S Adler, P J Baker, R J Johnson, R F Ochi, P Pritzl, W G Couser
Journal: Journal of Clinical Investigation (1986)

To explore possible mechanisms by which complement membrane attack complexes (MAC) that are deposited in the glomerular mesangium might be pathogenic, we stimulated rat glomerular mesangial cells grown in vitro with nascent MACs formed from the purified human complement components C5b6 and normal human serum and measured production of superoxide ion (O2-) and hydrogen peroxide (H2O2). Mesangial cells incubated with C5b6 + serum, which results in cell membrane interaction with the MAC, produce 0.9 +/- 0.15 nmol O2-/10(5) cells per 30 min, which was significantly greater than the amount produced by cells incubated with C5b6 alone, serum alone, or decayed MACs that can no longer interact with the cell membrane (0.3 +/- 0.2, 0.4 +/- 0.1, 0.3 +/- 0.2 nmol O2-/10(5) cells per 30 min, respectively; P less than 0.02). Production of O2- after stimulation with MACs increased during the first 20 min of incubation but then plateaued. Cells exposed to decayed MACs produced small amounts of O2-, which did not increase from 20 to 60 min. Production of H2O2 was also observed after stimulation with MACs, and continued to increase during 60 min of incubation (1.22 +/- 0.16 nmol H2O2/10(5) cells per 60 min), whereas H2O2 production could not be detected after exposure to decayed MACs. Cell viability was not adversely affected by exposure to nascent MACs as determined by trypan blue exclusion or chromium-51 release. These results demonstrate that glomerular mesangial cell membrane interaction with the MAC stimulates the production of the toxic oxygen metabolites O- and H2O2. Activation of the terminal complement pathway by mesangial immune deposits in vivo might lead to tissue injury by stimulation of local production of toxic oxygen-free radicals.
Clearance of Clara Cell Secretory Protein 16 (CC16) and Surfactant Proteins A and B from Blood in Acute Respiratory Failure
Authors: IAN R. DOYLE, CEDRIC HERMANS, ALFRED BERNARD, TERENCE E. NICHOLAS, ANDREW D. BERSTEN
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Surfactant proteins A and B (SP-A and SP-B) enter the circulation in a manner that acutely reflects changes in pulmonary function in patients with acute respiratory failure (ARF). There is a small but significant gradient in SP-A and SP-B from arterial to mixed venous (A–V) blood, and since we have detected both proteins in urine, the kidney may be a major site of their systemic clearance. Clara cell secretory protein 16 (CC16), which leaks from the respiratory tract, is known to be freely eliminated by the kidney. Lung plasma protein levels will depend on the rates of both protein entry into and clearance from plasma. In order to study the limiting variable determining these levels, we compared plasma CC16, SP-A, and SP-B in matching A–V blood samples from 37 ARF patients with indices of lung dysfunction and glomerular filtration rate (GFR) (of plasma cystatin C and creatinine). Cystatin C, CC16, SP-A, and SP-B were reduced in mixed venous plasma (all p < 0.001) and their A–V gradients were directly related to their arterial levels (all p < 0.03). Whereas CC16, SP-A, and SP-B reflected blood oxygenation (all p < 0.05), only SP-A and SP-B were related to lung injury score (LIS) (both p < 0.05). In contrast, whereas the clearances of both CC16 and cystatin C were related to that of creatinine (p < 0.02 for both), the clearances of SP-A and SP-B were not. Our study confirms that all three lung proteins are acutely cleared from the circulation of patients with ARF (half-lives < 18 min), and we conclude that whereas the plasma concentration of CC16 depends on GFR, plasma concentrations of SP-A and SP-B reflect lung function independently of this variable.
Abstract 3717: Corrected Qt Interval (qtc) Is Prolonged In Metabolic Syndrome Population
Authors: Weiju Li, Yongyi Bai, Kai Sun, Jingzhou Chen, Yibo Wang, Weili Zhang, Xiaodong Song, Xiaohan Fan, Shuxia Wang, Xiaomin Yang, Yunfeng Han
Journal: Circulation (2007)

Background : Prolonged corrected QT interval (QTc) is a risk factor for cardiovascular disease, recent studies suggested that patients with metabolic syndrome had significantly higher values of QTc, but those studies were conducted in small sample, the result should be verified in large population. Purpose : The study is to evaluate the relationship between QTc and metabolic syndrome in large population and to elucidate the possible pathophysiological mechanism. Methods: The date was collected in a hypertensive survey in rural China, a total of 5467 individuals (men 3667, women 1800), aged from 20 to 80 years, were enrolled. Subjects with history of coronary heart disease, valvular heart disease, stroke, hepatic, renal, thyroid diseases and all kinds of arrhythmia (recorded by 12 lead ECGs) were excluded. Electrocardiogram was recorded and the value of QTc was calculated using Bazett’s equation. All individuals had ultrasonic echocardiograph examination and blood test. Using revised NCEP-ATPIII definition, 2271 individuals were diagnosed with metabolic syndrome, 3128 were non-metabolic syndrome. Results: Both men and women individuals with metabolic syndrome had longer QTc than those with no metabolic syndrome (404.1±30.7ms vs 407.6±31.5 ms, p&lt;0.05; 412.3±32.1 ms vs 417.5 ±32.4ms, p&lt;0.001 respectively). The value of QTc increased with the number of abnormal metabolic parameters. After adjusted age and sex, QTc is negatively correlated to serum potassium concentration and positively correlated with posterior left ventricular wall and intraventricular septum in both men and womem. Conclusion: Metabolic syndrome, even its single component is a risk factor for prolonged QTc. As metabolic syndrome individuals have lower serum potassium concentration and thicker posterior left ventricular wall and intraventricular septum than non-metabolic syndrome individuals, we propose that low serum potassium concentration and myocardial hypertrophy might play important roles in the development of prolonged QTc in metabolic syndrome.
Angiotensin II Receptor Blockers and Nephropathy Trials
Authors: Zachary T. Bloomgarden
Journal: Diabetes Care (2001)

This is the first of a series of reports on the American Diabetes Association (ADA) 61st Scientific Sessions held in Philadelphia in June 2001. It covers topics related to angiotensin II receptor blockers (ARBs) and nephropathy.

At a symposium at the 61st Scientific Sessions of the ADA in June 2001, the results of three recent diabetic nephropathy trials with angiotensin II subtype 1 receptor antagonists were presented. Hans-Henrik Parving, Gentofte, Denmark, pointed out that kidney disease develops in 40% of patients with type 2 diabetes, with 25% of patients in Europe and 46% in the U.S. with end-stage renal disease (ESRD) having diabetes. In the latter population, the proportion increases annually by 1.5%. In type 2 diabetes, microalbuminuria is associated with a 5–10% lifetime risk of progression to overt nephropathy, while patients with normoalbuminuria have a 10- to 20-fold lower risk. In the Irbesartan for Micro-Albuminuria in Type 2 Diabetes (IRMA) study, 590 patients with 20–200 μg/min albuminuria with normal serum creatinine and with blood pressure (BP) >135/85 mm Hg were randomized to placebo or 150 or 300 mg irbesartan daily for 2 years. The mean age was 58 years; 70% were male; all were Caucasian; baseline BP was 153/90 mm Hg; baseline albuminuria was 55 μg/min; baseline glomerular filtration rate (GFR) was 110 ml/min; and baseline HbA1c was 7.2%. Patients treated with aspirin in a dose exceeding 325 mg daily were excluded because of the effect on proteinuria and renal function. The mean trough BP (measured 24 h after the last dose of medication) during the study was 145/84, 143/84, and 142/84 mm Hg with placebo and 150 and 300 mg irbesartan daily, respectively. Progression to macroalbuminuria occurred in 15, 10, and 5%, respectively, of the three groups at 2 years, with adjusted risk reduction of 68% with 300 mg and …
KSR2 Is an Essential Regulator of AMP Kinase, Energy Expenditure, and Insulin Sensitivity
Authors: Diane L. Costanzo-Garvey, Paul T. Pfluger, Michele K. Dougherty, Jeffery L. Stock, Matthew Boehm, Oleg Chaika, Mario R. Fernandez, Kurt Fisher, Robert L. Kortum, Eun-Gyoung Hong, John Y. Jun, Hwi Jin Ko, Aimee Schreiner, Deanna J. Volle, Tina Treece, Amy L. Swift, Mike Winer, Denise Chen, Min Wu, Lisa R. Leon, Andrey S. Shaw, John McNeish, Jason K. Kim, Deborah K. Morrison, Matthias H. Tschöp, Robert E. Lewis
Journal: Cell Metabolism (2009)
Aspirin renography to detect unilateral renovascular hypertension
Authors: Masahito Imanishi, Michiko Yano, Kohei Hayashida, Yoshio Ishida, Makoto Takamiya, Genjiro Kimura, Shunichi Kojima, Yuhei Kawano, Yohkazu Matsushima, Hiroaki Matsuoka, Teruo Omae
Journal: Kidney International (1994)
A yeast estrogen screen for examining the relative exposure of cells to natural and xenoestrogens.
Authors: S F Arnold, M K Robinson, A C Notides, L J Guillette, J A McLachlan
Journal: Environmental Health Perspectives (1996)

Xenoestrogens, such as o,p'-DDT and octyl phenol (OP), have been associated with reproductive abnormalities in various wildlife species. Xenoestrogens mimic the natural estrogen 17 beta-estradiol and compete for binding to the estrogen receptor. Even though the affinity of o,p'-DDT and OP for the estrogen receptor is approximately 1000-fold lower than 17 beta-estradiol, the actions of xenoestrogens could be enhanced if their bioavailability in serum were greater than 17 beta-estradiol. To test this hypothesis, the yeast estrogen screen (YES) was created by expressing human estrogen receptor (hER) and two estrogen response elements (ERE) linked to the lacZ gene. The beta-galactosidase activity of the YES system was significantly increased after treatment with 17 beta-estradiol or the xenoestrogens diethylstilbestrol (DES), o,p'-DDT, and OP but not with vehicle, antiestrogen ICI 164,384, dexamethasone, or testosterone. To determine whether serum proteins affected the bioavailability of natural estrogens compared to xenoestrogens, albumin, sex hormone binding globulin (SHBG), or charcoal-stripped serum were added to the YES system and beta-galactosidase activity assayed. Albumin and SHBG decreased beta-galactosidase activity in the presence of estradiol to a greater extent than DES, o,p'-DDT, and OP. Human and alligator charcoal-stripped serum were also effective at selectively reducing beta-galactosidase activity in the presence of estradiol compared to xenoestrogens. Human serum was more effective than alligator serum in reducing beta-galactosidase activity in the presence of xenoestrogens, indicating that serum may serve as a biomarker for sensitivity to xenoestrogens. Selective binding of 17 beta-estradiol by proteins in serum indicates that certain xenoestrogens may exert greater estrogenicity than originally predicted. The estrogenic potency of a compound involves its binding affinity, bioavailability in serum, and persistence in the environment. Our data demonstrate the utility of the YES system for identifying and characterizing environmental estrogens.