tbuckley/cabot-search huggingface dataset:
<scp>F</scp>cε<scp>RI</scp> stimulation promotes the differentiation of histamine receptor 1‐expressing inflammatory macrophages
Authors: N. Novak, W. M. Peng, T. Bieber, C. Akdis
Journal: Allergy (2013)

Abstract Background Monocyte differentiation into dendritic cells or macrophages and recruitment to peripheral organs in chronic inflammatory diseases are directed by allergen challenge via F cε RI as well as the nature of soluble factors in the microenvironment. High‐affinity receptor for IgE stimulation of effector cells results in the release of histamine, which acts on various histamine receptors ( HR ) 1‐4, expressed by immune cells. Methods We examined the effect of F cε RI stimulation of human monocytes on H 1 R expression and function of differentiating cells. The m RNA levels of H 1 R , H 2 R and histidine decarboxylase of differentiating cells were detected by quantitative real‐time PCR . Expression of CD 1c, CD 11c, CD 68 and CD 163 was detected by flow cytometry. Amount of histamine, IL ‐6 and IL ‐12p70 in the cell culture was measured with the help of cytometric bead arrays or ELISA assays. Numbers of H 1 R ‐expressing macrophages were evaluated by immunofluorescence double staining of CD 68 and H 1 R on human skin sections. Results We demonstrated that F cε RI stimulation promotes the generation of H 1 R ‐expressing macrophage‐like cells with enhanced histamine biosynthesis and H 1 R ‐mediated proinflammatory properties. Supporting our in vitro findings, high numbers of H 1 R ‐expressing CD 68 pos macrophages were detected in the dermis of atopic dermatitis ( AD ) skin lesions. Conclusion Our observations point to a close histamine‐/ HR ‐mediated activation of dermal macrophages, leading to modified cell differentiation and responsiveness via H 1 R , which might contribute to the aggravation of allergic skin inflammation in AD .
A Dependent-Rates Model and an MCMC-Based Methodology for the Maximum-Likelihood Analysis of Sequences with Overlapping Reading Frames
Authors: Anne-Mette Krabbe Pedersen, Jens Ledet Jensen
Journal: Molecular Biology and Evolution (2001)

We present a model and methodology for the maximum-likelihood analysis of pairwise alignments of DNA sequences in which two genes are encoded in overlapping reading frames. In the model for the substitution process, the instantaneous rates of substitution are allowed to depend on the nucleotides occupying the sites in a neighborhood of the site subject to substitution at the instant of the substitution. By defining the neighborhood of a site to extend over all sites in the codons in both reading frames to which a site belongs, constraints imposed by the genetic code in both reading frames can be taken into account. Due to the dependency of the instantaneous rates of substitution on the states at neighboring sites, the transition probability between sequences does not factorize and therefore cannot be obtained directly. We present a Markov chain Monte Carlo procedure for obtaining the ratio of two transition probabilities between two sequences under the model considered, and we describe how maximum-likelihood parameter estimation and likelihood ratio tests can be performed using the procedure. We describe how the expected numbers of different types of substitutions in the shared history of two sequences can be calculated, and we use the described model and methodology in an analysis of a pairwise alignment of two hepatitis B sequences in which two genes are encoded in overlapping frames. Finally, we present an extended model, together with a simpler approximate estimation procedure, and use this to test the adequacy of the former model.
Targeting Bcl-2 family members with the BH3 mimetic AT-101 markedly enhances the therapeutic effects of chemotherapeutic agents in in vitro and in vivo models of B-cell lymphoma
Authors: Luca Paoluzzi, Mithat Gonen, Jeffrey R. Gardner, Jill Mastrella, Dajun Yang, Jon Holmlund, Mel Sorensen, Lance Leopold, Katia Manova, Guido Marcucci, Mark L. Heaney, Owen A. O'Connor
Journal: Blood (2008)
Treatment compliance and self-medication in asthma in France
Authors: S Pretet, S Perdrizet, N Poisson, JC Pujet, J Marsac
Journal: European Respiratory Journal (1989)

A study was carried out among asthmatic patients in order to determine their compliance to treatment and self-medication. Data collection used a self-administered postal questionnaire as tested in a previous study. The population under study included 450 asthmatic patients; 370 answered; their mean age was 47 +/- 16 yrs and 44% were men. An aerosol was the preferred route of administration (41%). Eighty two percent of the patients tended to reduce the doses following improvement; 80% claimed to know treatment for attacks; 90% had already been using an inhaler, although only 62% had been shown how to use one. Forty eight percent had already bought drugs without prescription, especially patients within the 25-34 yrs age group. This study is consistent with similar surveys performed in other populations. Improved quality of information about treatments and how to use drugs is higher in patients with chronic forms of asthma involving unpredictable acute attacks.
Ernest Henry Starling, His Predecessors, and the “Law of the Heart”
Authors: Arnold M. Katz
Journal: Circulation (2002)

T he discovery that end-diastolic volume regulates the work of the heart is generally credited to Ernest Henry Starling, who described this relationship in a series of papers between 1912 and 1914 [1][2][3][4] and in his Linacre Lecture, which was given at Cambridge University in 1915 and published in 1918. 5In these papers, Starling and his collaborators acknowledge that they were not the first to describe this relationship 6 ; they cite the work of Blix 7 and Evans and Hill 8 on the length-dependence of energy release by skeletal muscle, Frank's 1895 description of the influence of diastolic volume on the work of the frog ventricle, 9 and contemporary descriptions in canine 10 and feline hearts. 11The present article reviews evidence that what we now call "Starling's Law of the Heart" or "The Frank-Starling Relationship" was widely appreciated by late 19th century physiologists.
Effects of Isoflavone Dietary Supplementation on Cardiovascular Risk Factors in Type 2 Diabetes
Authors: Susana González, Vijay Jayagopal, Eric S. Kilpatrick, Tom Chapman, Stephen L. Atkin
Journal: Diabetes Care (2007)

A diet supplemented with soy protein and isoflavones has been shown to reduce cardiovascular risk factors in postmenopausal women with type 2 diabetes. However, it remains unclear which component is responsible for these effects. Our aim was to determine whether the addition of isoflavones alone modifies cardiovascular disease risk markers in this group of patients. Cardiovascular disease (CVD) is the leading cause of mortality in women in developed countries (1), and women with diabetes are four times more likely to die from CVD than men (2). Among other factors, postmenopausal estrogen depletion, greater insulin resistance, and dyslipidemia (3,4) may contribute to high risk of accelerated CVD.

Modification of lifestyle is important to reduce CVD risk factors and delay progression of type 2 diabetes–associated complications. In particular, the addition of oral supplements, such as soy products, as part of a healthy diet has attracted recent interest because of their beneficial effects on lipid profiles (5–10). However, scant information is available on the effects of soy in individuals with type 2 diabetes (11–13), who are at higher risk due to hyperlipidemia, lower HDL levels, and abnormalities in LDL/lipoprotein composition (14). It also remains unclear whether a beneficial effect can be attributed to the soy protein or isoflavones. …
Effect of endoscopic sphincterotomy on gall bladder bile lithogenicity and motility
Authors: B C Sharma, D K Agarwal, S S Baijal, T S Negi, G Choudhuri, V A Saraswat
Journal: Gut (1998)

Background —Endoscopic sphincterotomy has been shown to inhibit stone formation in the gall bladder of experimental animals. Aims —To investigate the alterations in bile composition and gall bladder motility after endoscopic sphincterotomy. Patients —A study was performed of gall bladder bile composition and gall bladder motility in patients with gallstone disease ((n = 20; age 40–60 years, median age 55 years: seven men), with gall bladder calculi (n = 12) and with diseased gall bladder (chronic inflammation) without gall bladder calculi (n = 8)), who had received endoscopic sphincterotomy for common bile duct stones. Age and sex matched disease controls comprised 20 patients with gallstone disease but without stones and an intact sphincter of Oddi (with gall bladder calculi (n = 10) and diseased gall bladder without gall bladder calculi (n = 10)). Methods —Gall bladder motility was assessed by ultrasound. Duodenal bile collected by nasoduodenal tube after stimulation of gall bladder by intravenous ceruletid infusion was analysed for cholesterol, phospholipid, and bile acid concentrations, cholesterol saturation index, and nucleation time. Results —There was a significant reduction in mean (SEM) fasting volume (12.5 (1.7) ml v 26.4 (2.5) ml; p&lt;0.001) and mean (SEM) residual volume (4.34 (0.9) ml v 14.7 (0.98) ml; p&lt;0.001), and increase in mean (SEM) ejection fraction (65.7 (4.2)% v 43.6 (5.52)%; p&lt;0.001) and mean (SEM) rate constant of gall bladder emptying (−0.031/min v −0.020/min; p&lt;0.01) in patients who had been subjected to endoscopic sphincterotomy. Median nucleation time was significantly longer (17 days v 6 days; p&lt;0.006) in treated patients. There was a reduction in total mean (SEM) lipid concentrations (6.73 (0.32) g/dl v 7.72 (0.84) g/dl; p&lt;0.05), cholesterol (5.6 (1.5) mmol/l v 10.3 (2.23) mmol/l; p&lt;0.001) and CSI (0.72 (0.15) v 1.32 (0.31); p&lt;0.001). There was no significant change in mean (SEM) phospholipid (25.6 (3.5) mmol/l v 23.4 (6.28) mmol/l) and bile acid (93.7 (7.31) mmol/l v 105.07 (16.6) mmol/l) concentrations. Conclusions —After endoscopic sphincterotomy there was enhanced contractility of the gall bladder, accompanied by a prolongation of nucleation time and reduction in cholesterol saturation index.
Factor‐X deficiency in amyloidosis: A critical review
Authors: Philip R. Greipp, Robert A. Kyle, E. J. Walter Bowie
Journal: American Journal of Hematology (1981)

Thirty cases of amyloidosis with factor-X deficiency, including six of our own, were reviewed. Modest deficiency of factor X was often associated with severe bleeding. In many of the cases, clinical bleeding could not be accounted for by deficiency of factor X alone. Other hemostatic defects were found in these patients and probably contributed to the bleeding. Modes of treatment, including the empiric use of corticosteroids and splenectomy, were discussed in light of current knowledge of pathogenesis of this unusual blood clotting disorder. This involves the interaction of amyloid fibrils and blood clotting factors.
Effects of enteropathogenic Escherichia coli on microvillar membrane proteins during organ culture of rabbit intestinal mucosa.
Authors: H Embaye, C A Hart, B Getty, J N Fletcher, J R Saunders, R M Batt
Journal: Gut (1992)

This study examines the effects of an enteropathogenic Escherichia coli on microvillar membrane proteins during organ culture of rabbit ileal explants. Explants maintained with enteropathogenic E coli showed brush border effacement affecting approximately 50% of enterocytes, and where enteropathogenic E coli were closely adherent to the enterocyte surface microvilli were apparently being shed as vesicles. The microvillar membrane enzymes alkaline phosphatase, aminopeptidase N and alpha-glucosidase were released into the culture medium during organ culture, and this process was significantly enhanced by enteropathogenic E coli. This increased loss of microvillar membrane enzymes into the culture medium was associated with decreased tissue activities of microvillar membrane enzymes in enteropathogenic E coli infected ileal explants compared with control. For aminopeptidase N in particular, however, total enzyme activities in the tissue plus culture medium were increased comparing enteropathogenic E coli with control, suggesting that there might be an increase in the rate of synthesis of certain microvillar membrane proteins. Reorientating sucrose density gradient centrifugation of culture medium showed that alkaline phosphatase, aminopeptidase N and alpha-glucosidase were predominantly associated with particles of peak modal density 1.19 g/ml in both groups, confirming that enteropathogenic E coli accelerate release of microvillar membrane enzymes as vesicles. Analytical fractionation of ileal explants showed that enteropathogenic E coli resulted in a loss of microvillar membrane enzyme activities from the main brush border peak of modal density 1.21 g/ml present in controls. The density of the remaining smaller and lighter peak increased from 1.19 g/ml to 1.23 g/ml after homogenisation in digitonin, confirming association of these proteins with cholesterol containing membranes and not endoplasmic reticulum. These findings suggest that enteropathogenic E. coli accelerate the normal shedding of microvillar membrane proteins as vesicles, and may stimulate a compensatory increase in microvillar membrane protein synthesis.
Osteomalacia Due to 1α,25-Dihydroxycholecalciferol Deficiency
Authors: Marc K. Drezner, Mark N. Feinglos
Journal: Journal of Clinical Investigation (1977)

Oncogenic osteomalacia is a syndrome in which unexplained osteomalacia remits after resection of a coexisting mesenchymal tumor. We have investigated the mechanism by which a giant cell tumor of bone caused biopsy-proved osteomalacia in a 42-yr-old woman. The biochemical abnormalities were: hypophosphatemia; decreased renal tubular maximum for the reabsorption of phosphate per liter of glomerular filtrate; negative calcium and phosphorus balance; hyperaminoaciduria; and subnormal calcemic response to exogenously administered parathyroid hormone. Malabsorption, hypophosphatasia, fluorosis, and acidosis were excluded as causes of the osteomalacia. Serum 25-hydroxycholecalciferol was normal (27±1 ng/ml). However, the serum concentration of 1α,25-dihydroxycholecalciferol was low (1.6±0.1 ng/100 ml). Oral administration of physiological amounts of 1α,25-dihydroxycholecalciferol resulted in resolution of the biochemical abnormalities of the syndrome and healing of the bone pathology. We suggest that tumor-induced inhibition of 1α,25-dihydroxycholecalciferol synthesis caused the osteomalacia. The causal role of the tumor was proved by demonstrating that resection was accompanied by roentgenographic evidence of bone healing and maintenance of normal serum phosphorus; renal tubular maximum for the reabsorption of phosphate; calcium and phosphorus balance; aminoaciduria; and calcemic response to exogenous parathyroid hormone.
A method for finding putative causes of gene expression variation
Authors: Reija Autio, Sampsa Hautaniemi, Markus Ringnér, Päivikki Kauraniemi, Henrik Edgren, Olli Yli-Harja, Jaakko Astola, Anne Kallioniemi, Olli-Pekka Kallioniemi
Journal: Cancer Research (2004)

The majority of microarray studies evaluate gene ex- pression differences between various specimens or con- ditions. However, the causes of this variability often re- main unknown. Our aim is to identify underlying causes of these patterns, a process that would eventually enable a mechanistic understanding of the deregulation of gene expression in cancer. The procedure consists of three phases: pre-processing, data integration and statistical analysis. We have applied the strategy to identify genes that are overexpressed due to amplification in breast cancer. The data were obtained from 14 breast cancer cell lines, which were subjected to cDNA microarray based copy number and expression experiments. The re- sult of the analysis was a list that consisted of 92 genes. This set includes several genes that are known to be both overexpressed and amplified in breast cancer. The com- plete study was published in Journal of the Franklin In- stitute 2004, and in this paper we focus on the main issues of the study. (Less)
Phase I and Pharmacokinetic Study of the Dolastatin-15 Analogue Tasidotin (ILX651) Administered Intravenously on Days 1, 3, and 5 Every 3 Weeks in Patients with Advanced Solid Tumors
Authors: Casey Cunningham, Leonard J. Appleman, Miora Kirvan-Visovatti, David P. Ryan, Eileen Regan, Svetislava Vukelja, Peter L. Bonate, Francis Ruvuna, Robert J. Fram, Antti Jekunen, Steve Weitman, Lisa A. Hammond, Joseph P. Eder
Journal: Clinical Cancer Research (2005)

Abstract Purpose: To determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and pharmacokinetics of tasidotin (ILX651), a dolastatin-15 analogue, when administered on days 1, 3, and 5 every 3 weeks in patients with advanced solid tumors. Patients and Methods: Thirty-two patients were treated with 92 courses of tasidotin through seven dose levels determined by a modified Fibonacci scheme ranging from 3.9 to 45.7 mg/m2. Pharmacokinetic samples were collected during the first course. Results: Neutropenia was the principal DLT at the 45.7 mg/m2/d dose level. In addition, one patient also experienced grade 3 neutropenia complicated with grade 3 esophageal candidiasis and grade 3 dehydration. Only 1 of 11 patients treated at the MTD, 34.4 mg/m2, experienced dose-limiting neutropenia. Other common, drug-related toxicities included mild to moderate fatigue, anemia, nausea, anorexia, emesis, alopecia, and diarrhea. The best observed antitumor response consisted of stable disease and was noted in 10 patients (31%); the median duration on study for those patients with stable disease was 99.5 days compared with 37.5 days for those patients with progressive disease. Tasidotin plasma concentrations declined biphasically with an effective half-life of ≤55 minutes, and ∼11% was excreted unchanged in the urine. Conclusion: The recommended dose for phase II studies and the MTD when tasidotin is administered on days 1, 3, and 5 every 3 weeks is 34.4 mg/m2. The favorable toxicity profile of tasidotin compared with other antitubulin agents, including other dolastatin analogues, and its novel mechanism of action support further disease-directed evaluation of this agent.
The hematopoietic system is a source of odorants that distinguish major histocompatibility types.
Authors: K Yamazaki, G K Beauchamp, L Thomas, E A Boyse
Journal: The Journal of Experimental Medicine (1985)

Radiation chimeras were made by restoring lethally irradiated inbred mice with bone marrow cells of F1 hybrid mice of crosses between that inbred strain and an H-2-congenic strain. The urine of these chimeras was tested by the Y maze method, and shown to have acquired a scent indicative of the reconstituting donors' H-2 type. Thus, cells of the hematopoietic system contribute to the H-2-related odorant properties that enable mice to distinguish one another according to their H-2 types.
Growing Importance of <i>MYC</i>/<i>BCL2</i> Immunohistochemistry in Diffuse Large B-Cell Lymphomas
Authors: Michael Pfreundschuh
Journal: Journal of Clinical Oncology (2012)

Prognostic Index (IPI), which was established to predict outcome of patients with aggressive lymphoma treated in the prerituximab era, has been confirmed to be a valid prognosticator for patients receiving rituximab, with the differences between the four risk groups (low, low-intermediate, high-intermediate, and high) being smaller, yet still significant in the rituximab era. 2 However, within each of these IPI risk groups, there are considerable differences in outcome, suggesting underlying biologic differences that are not encompassed by the clinical parameters lactate dehydrogenase, age, advanced stage, performance state, and two or more extralymphatic sites of involvement. By gene expression profiling (GEP), DLBCL can be stratified into biologically and prognostically relevant subtypes 3,4 based on cell-of-origin (COO) gene signatures, with the activated B-cell type being associated with an inferior outcome com
Identification and characterization of specific binding proteins for growth hormone in normal human sera.
Authors: A C Herington, S Ymer, J Stevenson
Journal: Journal of Clinical Investigation (1986)

The well-recognized "big" forms (45,000-100,000 mol wt) of immunoreactive human growth hormone (hGH) in human serum have been reported to be random aggregates or formal polymers. However, we have now investigated the possibility that they are protein-bound forms. After incubation of monomeric 125I-hGH with normal serum, gel chromatography indicated a peak of bound 125I-hGH (at approximately 120,000 mol wt), which was completely displaced by excess unlabeled hGH. When serum alone was chromatographed two peaks of specific binding were subsequently detected, the major peak, eluting between 74,000 and 85,000 mol wt corresponded to the 125I-hGH-binding protein complex observed at approximately 120,000 mol wt. Using a mini-gel filtration system for separating bound from free hormone, binding of 125I-hGH by normal human serum was dependent on time (equilibrium was reached in 2 h at 21 degrees C), temperature (21 degrees C greater than 37 degrees C), Ca2+ and serum concentrations. Binding was reversible and highly specific for hGH, not being displayed by GH or prolactins from several species. Scatchard analysis revealed linear plots with an affinity (KA) of 0.32 +/- 0.06 X 10(9) M-1 (n = 7). Human serum with low endogenous hGH levels, when added to rabbit liver membranes, decreased the binding of 125I-hGH in this tissue in a dose-dependent manner. These data indicate that human sera contain a specific, high affinity binding protein for hGH and that this may account, at least in part, for the known size heterogeneity of GH in serum. Its effect on GH binding to target tissues may indicate a role for the binding protein in the regulation of GH action.
Possible Role of Oxidative Stress in the Pathogenesis of Hypertension
Authors: Antonio Ceriello
Journal: Diabetes Care (2008)

Recently oxidative stress has been proposed as the cause of hypertension. An imbalance in superoxide and nitric oxide production may account for reduced vasodilation, which in turn can favor the development of hypertension. In vitro and in human studies support this hypothesis. The supplementation of antioxidants, particularly in the form of fresh fruit and vegetables, reduces blood pressure, supporting a role for free radicals in hypertension.
How many representations of the body?
Authors: Frédérique de Vignemont
Journal: Behavioral and Brain Sciences (2007)

Abstract Based on functional differences, Dijkerman &amp; de Haan (D&amp;dH) emphasize the duality of somatosensory processing, and therefore of body representations. But how many body representations do we really have? And what kind of criterion can we use to distinguish them? I review here the empirical and conceptual difficulties in drawing such distinctions, and the way to progress.