tbuckley/cabot-search huggingface dataset:
Effect of lemakalim on action potentials, intracellular calcium, and contraction in guinea pig and human cardiac myocytes
Authors: C. Jiang, S. Mochizuki, P. A Poole-Wilson, S. E Harding, K. T MacLeod
Journal: Cardiovascular Research (1994)

The aim was to investigate the effects of lemakalim on action potential duration, intracellular free calcium ([free Ca2+]i), and cell contraction in human and guinea pig cardiac myocytes. In addition, the possible modulation by pH of lemakalim induced activation of ATP sensitive potassium (KATP) channels was assessed.Single ventricular myocytes were enzymatically dissociated from adult male guinea pigs (300-600 g). Single myocytes were isolated from human ventricular tissues. Cells were loaded with the acetoxymethyl ester form of fura-2 to monitor changes in [free Ca2+]i and subjected to conventional electrophysiological techniques.In guinea pig cells, lemakalim (3, 10, 30 microM) reduced action potential duration in a concentration dependent manner. This decrease was accompanied by hyperpolarisation of the resting membrane potential. Lemakalim (3, 10, 30 microM) reduced the systolic fura-2 fluorescence ratio without having a significant effect on diastolic fluorescence and also reduced the cell contraction in concentration dependent manner. Glibenclamide (1 microM), a specific inhibitor of KATP channels, did not affect action potential duration, fura-2 fluorescence ratio, or cell contraction in the absence of lemakalim. However, the same dose of glibenclamide markedly inhibited the lemakalim induced decrease in action potential duration, fura-2 fluorescence ratio, and cell contraction. Reducing extracellular pH enhanced the decrease in action potential duration induced by lemakalim. In human ventricular myocytes, lemakalim (3, 10 and 30 microM) caused a decrease in action potential duration and systolic fura-2 fluorescence ratio. The reduction in action potential duration and fura-2 fluorescence ratio was also reversed by glibenclamide (1 microM).These results suggest that lemakalim reduces systolic [free Ca2+]i by activating ATP sensitive potassium channels which results in a decrease of action potential duration in guinea pig and human ventricular myocytes. The reduction in [free Ca2+]i mediates the negative inotropic effect induced by lemakalim. In addition, pH may modulate the KATP channel activation by the channel opener.
Sleep and Wakefulness
Authors: George L. Engel
Journal: JAMA (1964)

The reissue in revised and enlarged form of Kleitman's classic work, first published in 1939, is a service mainly to scholars, who will welcome a compilation of much of the world literature on sleep. But as a compilation, the book suffers badly from the author's unwillingness to weed out a host of worthless references, many of which are reported with disarming credulity. The extensive bibliography lists 4,337 titles, but unfortunately the format and typography make it very difficult to pick out the names of the authors, even though listed alphabetically. The index is inadequate, considering that the volume is mainly valuable as a reference source. In addition there are numerous typographical errors. The use of capital letters to indicate overlong terms, as BSRF, ARAS, LVFA, DTPS, would have been forgivable if a convenient glossary had been provided. The author certainly deserved better editorial assistance from a university press which should
Mucosal immune responses to HIV-1 in elite controllers: a potential correlate of immune control
Authors: April L. Ferre, Peter W. Hunt, J. William Critchfield, Delandy H. Young, Megan M. Morris, Juan C. Garcia, Richard B. Pollard, Hal F. Yee, Jeffrey N. Martin, Steven G. Deeks, Barbara L. Shacklett
Journal: Blood (2008)
Mineralocorticoid secretion in essential hypertension with normal and low plasma renin activity.
Authors: F H Messerli, O Kuchel, W Nowaczynski, K Seth, M Honda, S Kubo, R Boucher, G Tolis, J Genest
Journal: Circulation (1976)

In 19 control subjects, 33 patients with essential hypertension and normal plasma renin activity (PRA) and 11 patients with low PRA, secretory rates of 18-hydroxy-11-deoxy-corticosterone (18-OH DOC), 11-deoxycorticosterone (DOC) and corticosterone were measured. Patients with low PRA were significantly older and had higher arterial pressure and slightly lower plasma potassium levels than patients with normal PRA. Mean 18-OH DOC secretion rate was higher in patients with normal PRA (603 +/- 112 SEM mug/24 hr) than in control subjects (219 +/- 19) and considerably higher (P less than 0.001) in patients with low PRA (1800 +/- 472). DOC and corticosterone secretion rates were within normal limits in most hypertensive patients. Plasma aldosterone was significantly higher in the hypertensive population than in control subjects whereas no significant difference was observed between the low- and normal-renin groups. A significant (P less than 0.01) mutual positive correlation was found between the secretion rates of 18-OH DOC, DOC and corticosterone in patients with low plasma renin activity. In contrast, there was no correlation between the secretion rates of the three mineralocorticoids in control subjects and patients with normal plasma renin activity. These data suggest a biosynthetic variation of the mineralocorticoid pathways in essential hypertension.
An array of mitochondrial alterations in the hepatocytes of long-evans cinnamon rats
Authors: Irmin Sternlieb, Nelson Quintana, Irene Volenberg, Michael L. Schilsky
Journal: Hepatology (1995)

In an attempt to identify the cellular targets of copper toxicity, we studied the ultrastructure of hepatocytes in the livers of 23 Long-Evans Cinnamon (LEC) rats ranging in age from 10 to 89 weeks. The hepatic copper concentration ranged from 325 to 2,126 (mean, 930) micrograms/g dry weight. Thirteen rats displayed varying degrees of jaundice at the time of killing. Numerous nuclei were indented by cytoplasmic invaginations. Conspicuous abnormalities were displayed by mitochondria. These included marked pleomorphism; increased or diminished matrical density; rearrangement, elongation, dilatation, stacking, or disappearance of cristae; absence of matrical granules; presence of matrical inclusions of flocculent electron-dense deposits; and degenerative changes. The severity of the ultrastructural changes did not correlate with the hepatic copper concentration but did correlate with the degree of the icterus displayed by the rats. Certain mitochondrial changes resembled those encountered in the hepatocytes of patients with Wilson's disease, confirming that these organelles are important targets of copper toxicity.
Antibody-induced loss of Friend virus leukemia cell surface antigens occurs during progression of erythroleukemia in F1 mice.
Authors: D Doig, B Chesebro
Journal: The Journal of Experimental Medicine (1978)

Friend virus (FV)-induced leukemic spleen cells from (B10.A X A)F1 mice were found to lose sensitivity to antibody-mediated lysis during progression of erythroleukemia. This was correlated with a 78% loss of FV-induced cell surface antigens as determined by quantitative absorption of cytotoxic antibodies and with a decreased percentage of leukemic spleen cells showing membrane immunofluorescence with anti-FV antibody. Antigen loss was observed only with virus-induced antigens, and was limited to antigens expressed on the cell surface. FV-induced antigens were regained when low-antigen leukemia cells from late stages of the leukemia were transferred to lethally irradiated nonimmune recipients, but not when these cells were transferred to hyperimmune lethally irradiated recipients. Conversely, when high-antigen leukemic spleen cells from early stages of the erythroleukemia were transferred to hyperimmune irradiated recipients, antigen loss was induced. The immune response to virus-induced antigens appeared to be involved in causing the antigenic changes observed on leukemia cells in this system.
Analysis of the systematic reviews process in reports of network meta-analyses: methodological systematic review
Authors: A. Bafeta, L. Trinquart, R. Seror, P. Ravaud
Journal: BMJ (2013)

<b>Objective</b> To examine whether network meta-analyses, increasingly used to assess comparative effectiveness of healthcare interventions, follow the key methodological recommendations for reporting and conduct of systematic reviews. <b>Design</b> Methodological systematic review of reports of network meta-analyses. <b>Data sources</b> Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Medline, and Embase, searched from inception to 12 July 2012. <b>Review methods</b> All network meta-analyses comparing clinical efficacy of three or more interventions based on randomised controlled trials, excluding meta-analyses with an open loop network of three interventions. We assessed the reporting of general characteristics and key methodological components of the systematic review process using two composite outcomes. For some components, if reporting was adequate, we assessed their conduct quality. <b>Results</b> Of 121 network meta-analyses covering a wide range of medical areas, 100 (83%) assessed pharmacological interventions and 11 (9%) non-pharmacological interventions; 56 (46%) were published in journals with a high impact factor. The electronic search strategy for each database was not reported in 88 (73%) network meta-analyses; for 36 (30%), the primary outcome was not clearly identified. Overall, 61 (50%) network meta-analyses did not report any information regarding the assessment of risk of bias of individual studies, and 103 (85%) did not report any methods to assess the likelihood of publication bias. Overall, 87 (72%) network meta-analyses did not report the literature search, searched only one database, did not search other sources, or did not report an assessment of risk of bias of individual studies. These methodological components did not differ by publication in a general or specialty journal or by public or private funding. <b>Conclusions</b> Essential methodological components of the systematic review process—conducting a literature search and assessing risk of bias of individual studies—are frequently lacking in reports of network meta-analyses, even when published in journals with high impact factors.
Nephrogenic Diabetes Insipidus Due to Demethylchlortetracycline Hydrochloride
Authors: Donald O. Castell
Journal: JAMA (1965)

SEVERAL reports have clearly documented the nephrotoxic effect of degraded tetracycline in producing an acquired, adult-type Fanconi syndrome.<sup>1</sup>We have recently studied a patient with polyuria and hyposthenuria following somewhat prolonged administration of demethylchlortetracycline hydrochloride (Declomycin), who did not exhibit any of the previously reported tetracycline-induced renal abnormalities. The medication was neither degraded nor outdated. We obtained stock numbers of the administered medication and determined that the drug was dispensed within the period of warranty and that it had been properly stored. <h3>Report of a Case</h3> A 26-year-old white male, a first lieutenant, in the US Marine Corps, was admitted to the US Naval Hospital, Bethesda, Md on May 22, 1964 for evaluation of polyuria and hyposthenuria. <h3>History of Present Illness.—</h3> In January 1963 the patient had been treated for nonspecific prostatitis while he was stationed at Camp Lejeune, NC. At that time he had symptoms of daytime urinary
Sucrase-alpha-dextrinase in the rat. Postinsertional conversion to inactive molecular species by a carbohydrate-free diet.
Authors: R Quan, G M Gray
Journal: Journal of Clinical Investigation (1993)

Absence of dietary carbohydrate decreases both activities of intestinal brush border sucrase-alpha-dextrinase. We examined the molecular mechanism causing this decrease. Adult rats were fed chow (70% CHO) or matched carbohydrate-free (CHO-free) diet for 7 d. Sucrase activity decreased by 50% in whole homogenates and brush borders. Enzyme kinetics revealed no change in sucrose affinity (CHO-free Km = 18 mM, chow Km = 21 mM), but fewer active sites (CHO-free Vmax = 2,720, chow Vmax = 5,000 mumol/min per g protein). Intraintestinal pulse-labeling of [35S]methionine in vivo revealed no differences in incorporation into sucrase. Immunoreactive sucrase protein, assayed by ELISA and rocket immunoelectrophoresis, increased twofold per milliunit of sucrase enzymatic activity in CHO-free jejunum. Total immunosucrase (St), the sum of active and inactive enzyme (St = Sa+Si), was unchanged with carbohydrate withdrawal, but > 50% of the sucrase protein became inactive. SDS-PAGE of sucrase immunoprecipitates revealed alteration of alpha, beta, and gamma subunits in CHO-free animals: (a) alpha and beta subunits migrated farther (mass change--2 kD); and (b) the alpha subunit became diffuse or was a doublet and was less abundant than the beta subunit. Rather than representing loss of sucrase protein, the decline in sucrase activity is achieved with structural subunit changes, probably involving postinsertional processing.
Assessment of effects of autonomic stimulation and blockade on the signal-averaged electrocardiogram.
Authors: J J Goldberger, M W Ahmed, M A Parker, A H Kadish
Journal: Circulation (1994)

Signal-averaged ECG is a noninvasive test designed to detect "late potentials." The effects of alterations in autonomic tone on the signal-averaged ECG have not been evaluated systematically.The effects of autonomic stimulation and blockade on the signal-averaged ECG were evaluated in 14 healthy subjects (8 men and 6 women; age, 28.5 +/- 4.8 years) on 2 separate days. The signal-averaged ECG was recorded at baseline and after physiological and pharmacologic beta-adrenergic stimulation (tilt, exercise, and epinephrine and isoproterenol infusions), sequential and combined beta-adrenergic and parasympathetic blockade, and alpha-adrenergic stimulation before and after parasympathetic blockade. Analysis was performed with a bidirectional filter (40-Hz high-pass). Significant changes in the signal-averaged QRS duration from baseline (105.1 +/- 12.0 milliseconds) were noted with tilt (96.8 +/- 8.8 milliseconds), tilt after double blockade (97.5 +/- 9.0 milliseconds), epinephrine (110.5 +/- 11.8 milliseconds), and isoproterenol (99.6 +/- 12.6 milliseconds). Changes in the root-mean-square voltage of the terminal 40 milliseconds and the low-amplitude (< 40 microV) signal duration paralleled the changes in the QRS duration.The signal-averaged ECG does not measure only "fixed" parameters but rather is altered under a variety of physiological and pharmacologic conditions. Upright tilt leads to shortening of the QRS duration before and after autonomic blockade; thus, the decrease in QRS duration with tilt may be related to factors other than changes in autonomic tone. These findings have implications for interpretation of the results of signal-averaged ECG.
Sclerosing sweat duct carcinoma of the eyelid margin
Authors: Mark T Duffy, Winston Harrison, Jodi Sassoon, Albert Hornblass
Journal: Ophthalmology (1999)

ObjectiveSclerosing sweat duct carcinoma (SSDC) is a rare, slow-growing, locally invasive skin tumor of eccrine and pilar origin. It is usually located on the face, particularly the upper lip, cheek, and forehead. It has been infrequently reported on the eyelid, secondarily involved from adjacent cheek and brow tumors. Only four previous cases have reported primary eyelid tumors. The authors present four cases of primary eyelid margin involvement, which show the variability in clinical presentations.DesignRetrospective case series. The authors present four case studies of lower eyelid margin tumors diagnosed as SSDC.Participants/methodsThe history of this recently recognized neoplasm is discussed in relation to the cases presented and the role of the ophthalmologist and pathologist in such cases.ResultsPrimary SSDC of the eyelid margin is a reportedly rare entity. This particular presentation can occur in all age groups; can mimic benign, acanthotic, or basal cell-like tumors; and is usually misdiagnosed initially. This can lead to a delay in definitive treatment for a tumor that classically presents late in its natural history to health professionals. All eight cases of primary eyelid SSDC now reported in the literature have occurred in the lower lid.ConclusionThis rare but aggressive tumor is difficult to diagnose from a simple biopsy and may be more common than previously believed. Initial or early diagnosis is important because of unusually invasive characteristics. Recurrence is common and usually leads to extensive tissue loss via direct invasion or subsequent wide resection. Correct histologic diagnosis at the time of initial tumor removal will likely aid in achieving complete excision with fewer recurrences.
Transfer Factor and Cellular Immune Deficiency Disease
Authors: Louis M. Sherwood, Edith E. Parris, H. Sherwood Lawrence
Journal: New England Journal of Medicine (1970)

SKIN tests performed with microbial antigens for the detection of delayed hypersensitivity have long been used in diagnostic medicine and are increasingly being applied to the investigation of disease. The diagnostic usefulness of this determination has resulted largely from two important characteristics of the host's response: a positive reaction is immunologically specific in that prior infection with the related microbe is an obligatory requirement; and a skin test performed with soluble microbial products does not usually by itself confer delayed cutaneous sensitivity on the negative subject. Hence, the tests are of value in detecting conversion to positive reactivity and thereby . . .
Experimental prestorage filtration removes antibodies and decreases lipids in RBC supernatants mitigating TRALI in vivo
Authors: Christopher C. Silliman, Marguerite R. Kelher, Samina Y. Khan, Monica LaSarre, F. Bernadette West, Kevin J. Land, Barbara Mish, Linda Ceriano, Samuel Sowemimo-Coker
Journal: Blood (2014)
Book Review The Eating Disorders Edited by A. James Giannini and Andrew E. Slaby. 286 pp., illustrated. New York, Springer-Verlag, 1993. $89. 0-387-94002-2 Endorphins, Eating Disorders and Other Addictive Behaviors By Hans F. Huebner. 272 pp. New York, W.W. Norton, 1993. $34.95. 0-393-70156-5
Authors: James E. Mitchell
Journal: New England Journal of Medicine (1993)
Regression of Established Tumors Expressing P-glycoprotein by Combinations of Adriamycin, Cyclosporin Derivatives, and MRK-16 Antibodies
Authors: T. Watanabe, T. Tsuruo, M. Naito, N. Kokubu
Journal: JNCI Journal of the National Cancer Institute (1997)

Overexpression of P-glycoprotein, a transmembrane protein capable of transporting a broad spectrum of anticancer drugs out of cells, likely contributes to tumor drug resistance. Strategies for overcoming this resistance include the use of specific compounds, such as cyclosporin derivatives, that modulate P-glycoprotein function and antibodies that bind to the protein, thereby altering its activity.We examined the antitumor activity of combination treatment with the anti-P-glycoprotein monoclonal antibody MRK-16, a cyclosporin derivative (either cyclosporin A [CsA] or PSC 833), and the anticancer drug Adriamycin (ADM) against human colorectal carcinoma cells in vitro and established xenografts of these cells in vivo.The human colorectal carcinoma cell line HCT-15 and its ADM-resistant subline HCT-15/ADM2-2 were used in this study. Cellular staining with a tetrazolium dye was used to assess the antitumor (i.e., antiproliferative) effects of treatment in vitro. Caliper measurement of tumor volumes was used to assess the antitumor effects of treatment in vivo. Cell surface binding of MRK-16 was measured by means of an immunofluorescence assay. Differences in the patterns of tumor cell growth in vitro and tumor growth rates in vivo were evaluated by means of repeated measure analysis of variance. Synergy in the combined effects of treatment was evaluated by means of the fractional product method.HCT-15 cells were found to express P-glycoprotein intrinsically; HCT-15/ADM2-2 cells expressed approximately five times more P-glycoprotein than the parental cells. HCT-15/ADM2-2 cells were also found to be about eight times more resistant to ADM in vitro than the parental cells. Incubation of both cell types in vitro with either MRK-16 and ADM or one of the cyclosporin derivatives and ADM inhibited cell growth minimally; however, ternary treatment with MRK-16, one of the cyclosporin derivatives, and ADM dramatically reduced the growth of both cell types. An analysis of treatment effects indicated that synergistic effects were obtained with ternary treatment. When athymic mice bearing established tumors (either HCT-15 or HCT-15/ADM2-2) were treated similarly with various combinations of the tested agents, the most pronounced antitumor effects were observed with ternary treatment. In some mice bearing HCT-15/ADM2-2 xenografts, ternary treatment led to complete tumor regression. Finally, CsA and PSC 833 were both shown to enhance MRK-16 binding to HCT-15 cells and HCT-15/ADM2-2 cells in vitro.Combination treatment with a cyclosporin derivative and an anti-P-glycoprotein antibody can be effective in circumventing P-glycoprotein-mediated drug resistance.
Seasonal Incidence in Clinical Onset of Hodgkin's Disease
Authors: K. W. Beetham
Journal: BMJ (1961)

<h3>ABSTRACT</h3> The sculpting of germ layers during gastrulation relies on coordinated migration of progenitor cells, yet the cues controlling these long-range directed movements remain largely unknown. While directional migration often relies on a chemokine gradient generated from a localized source, we find that zebrafish ventrolateral mesoderm is guided by the uniformly expressed and secreted protein Toddler/ELABELA/Apela, acting as a self-generated gradient. We show that the Apelin receptor, which is specifically expressed in mesodermal cells, has a dual role during gastrulation, acting as a scavenger receptor to generate a Toddler gradient, and as a chemokine receptor to sense this guidance cue. Thus, we uncover a single receptor-based self-generated gradient as the enigmatic guidance cue that can robustly steer the directional migration of mesoderm through the complex and continuously changing environment of the gastrulating embryo. <h3>One sentence summary</h3> Aplnr has a dual role to self-generate and sense a Toddler gradient directing mesodermal cells during zebrafish gastrulation.
Chromosomal High-Polysomies Predict Tumour Progression in T1 Transitional Cell Carcinoma of the Bladder
Authors: M.J. Ribal, A. Alcaraz, L. Mengual, A. Carrio, A. Lopez-Guillermo, C. Mallofré, J. Palou, A. Gelabert, H. Villavicencio
Journal: European Urology (2004)
Molecular characterization of invasive serogroup Y Neisseria meningitidis strains isolated in the Latin America region
Authors: Raquel Abad, Clara I. Agudelo, M. Cristina Brandileone, Grettel Chanto, Jean Marc Gabastou, Juan Carlos Hormazabal, M. Cecilia O Gorla, Aurora Maldonado, Jaime Moreno, Erwan Muros-Le Rouzic, Robert Lersch, Mabel Regueira, Celia Salcedo, Cecilia Sorhouet, Julio A. Vázquez
Journal: Journal of Infection (2009)