tbuckley/cabot-search huggingface dataset:
Primary autoimmune myelofibrosis: Definition of a distinct clinicopathologic syndrome
Authors: Vinod Pullarkat, Randall D. Bass, Jerald Z. Gong, Donald I. Feinstein, Russell K. Brynes
Journal: American Journal of Hematology (2002)

Myelofibrosis is characterized by reticulin fibrosis of the bone marrow with resulting features of myelophthisis. Besides hematopoietic malignancies and other neoplasms involving the bone marrow, myelofibrosis has been described in association with autoimmune disorders, especially systemic lupus erythematosus. We describe the clinicopathologic features of a primary form of autoimmune myelofibrosis (AIMF) in patients who do not have systemic lupus erythematosus or another well-defined autoimmune syndrome. Absence of marked splenomegaly, peripheral blood cytopenias with mild teardrop poikilocytosis and leukoerythroblastosis, bone marrow lymphoid aggregates, and presence of autoantibodies are some of the salient features of primary AIMF. AIMF should especially be differentiated from chronic idiopathic myelofibrosis, a neoplastic myeloproliferative disease. Primary AIMF appears to have an excellent prognosis, with all patients reported in this series responding to a short course of corticosteroid therapy.
Comparison of the Eder-Puestow and Celestin techniques for dilating benign oesophageal strictures.
Authors: K R Hine, C J Hawkey, M Atkinson, G K Holmes
Journal: Gut (1984)

The Celestin and Eder-Puestow methods of dilating benign oesophageal strictures have been compared prospectively in a randomised trial. One hundred and thirty three dilatations were performed on 72 patients. There was no significant difference between the two techniques with regard to the long term relief of symptoms. Celestin dilatation was quicker, less likely to cause pharyngeal trauma, and less damaging to guide wires. It could not be used, however, in those patients in whom only a short length of guide wire could be passed through the stricture.
Impact of maternal postnatal depression on cognitive development of young children.
Authors: S R Cogill, H L Caplan, H Alexandra, K M Robson, R Kumar
Journal: BMJ (1986)

Ninety four women and their first born children took part in a longitudinal study of maternal mental health during pregnancy and after delivery. The children9s cognitive functioning was assessed at age 4 using the McCarthy scales, without knowledge of the mothers9 psychiatric history or current health. As expected girls performed slightly better than boys and children from middle class and professional families did better than children from working class homes, as did children whose mothers had achieved at least one A level at school. Significant intellectual deficits were found in the children whose mothers had suffered with depression, but only when this depression occurred in the first year of the child9s life. Marital conflict and a history of paternal psychiatric problems were independently linked with lower cognitive test scores; together with a working class home background these were the only factors that contributed to the deleterious effect of maternal postnatal depression.
Whole Chloroplast Genome Comparison of Rice, Maize, and Wheat: Implications for Chloroplast Gene Diversification and Phylogeny of Cereals
Authors: Yoshihiro Matsuoka, Yukiko Yamazaki, Yasunari Ogihara, Koichiro Tsunewaki
Journal: Molecular Biology and Evolution (2002)

The fully sequenced chloroplast genomes of maize (subfamily Panicoideae), rice (subfamily Bambusoideae), and wheat (subfamily Pooideae) provide the unique opportunity to investigate the evolution of chloroplast genes and genomes in the grass family (Poaceae) by whole-genome comparison. Analyses of nucleotide sequence variations in 106 cereal chloroplast genes with tobacco sequences as the outgroup suggested that (1) most of the genic regions of the chloroplast genomes of maize, rice, and wheat have evolved at similar rates; (2) RNA genes have highly conservative evolutionary rates relative to the other genes; (3) photosynthetic genes have been under strong purifying selection; (4) between the three cereals, 14 genes which account for about 28% of the genic region have evolved with heterogeneous nucleotide substitution rates; and (5) rice genes tend to have evolved more slowly than the others at loci where rate heterogeneity exists. Although the mechanism that underlies chloroplast gene diversification is complex, our analyses identified variation in nonsynonymous substitution rates as a genetic force that generates heterogeneity, which is evidence of selection in chloroplast gene diversification at the intrafamilial level. Phylogenetic trees constructed with the variable nucleotide sites of the chloroplast genes place maize basal to the rice-wheat clade, revealing a close relationship between the Bambusoideae and Pooideae.
Acute β-Blockade Increases Muscle Sympathetic Activity and Modifies Its Frequency Distribution
Authors: Chiara Cogliati, Simona Colombo, Tomaso Gnecchi Ruscone, Domenico Gruosso, Alberto Porta, Nicola Montano, Alberto Malliani, Raffaello Furlan
Journal: Circulation (2004)

Background— The possible mechanisms by which β-adrenergic antagonists may act on the neural regulation of the cardiovascular system are still elusive. Recent studies reported a marked increase of postganglionic muscle sympathetic nerve activity (MSNA) after acute β-blockade associated with unchanged values of arterial blood pressure and baroreflex sensitivity. We tested the hypothesis that acute β-blockade might also alter the oscillatory characteristics of MSNA, thus decreasing its effectiveness on peripheral vasoconstriction. Methods and Results— In 11 healthy volunteers, ECG, MSNA, arterial pressure, and respiration were recorded before and after atenolol (0.05 mg/kg IV bolus) administration. The frequency distribution of RR interval, MSNA, systolic arterial pressure (SAP), and respiratory variability was assessed by spectrum and cross-spectrum analysis. Spontaneous baroreflex sensitivity (α-index) and plasma catecholamines (high-performance liquid chromatography) were measured. Atenolol induced a significant increase in RR interval (14.3±1.6%) with no changes in systolic and diastolic arterial pressure. MSNA increased (42±13% from 18±2 bursts per minute). The low-frequency (LF) component of RR and MSNA variability decreased (−44±7% and −24±5%, respectively), whereas the high-frequency (HF) component increased (163±55% and 34±11%, respectively), expressed in normalized units. Spectral coherence, an index of oscillatory coupling, decreased between LF RR and LF MSNA , whereas it increased between HF MSNA and HF Resp . SAP variability, α-index, and plasma catecholamines remained unchanged. Conclusions— Atenolol induced a change in MSNA frequency distribution reflecting a stronger respiratory coupling. This shift toward high frequency, despite an increase in MSNA, may lead to a less efficient sympathetic vasomotor modulation.
ABC of Medical Computing: AN INTRODUCTION TO COMPUTING IN MEDICAL PRACTICE
Authors: N. Lee, A. Millman
Journal: BMJ (1995)

The past decade has seen an explosive growth in the number of computers, and in Britain alone there are now over 10 million in use. The capability of computers has also increased so that today's desktop PC is far more powerful than older main frame computers. This breathtaking pace of change has inevitably left many people behind. It is extraordinary that, despite the fact that information technology is now taught in every school, only a minority of current medical students consider themselves computer literate. The proportion of practising doctors who are able to get the best out of a computer is even smaller. We hope to remove some of the mystique from computing and to share our confidence that the technology can easily be mastered.

Modern desktop PC.

**FIGURE OMITTED**

The commonest reason for buying a computer is the need to write simple letters, medical reports, papers, and curriculum vitae using a word processor. Most modern word processors are, however, capable of handling far more than simple text. You can create and incorporate colourful …
DETANONOate, a Nitric Oxide Donor, Decreases Amiloride-sensitive Alveolar Fluid Clearance in Rabbits
Authors: VANCE G. NIELSEN, MANUEL S. BAIRD, LAN CHEN, SADIS MATALON
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Inhaled nitric oxide (NO) has been administered to animals to selectively reduce pulmonary hypertension via NO donors such as the NONOates. However, vectorial Na+ transport across confluent monolayers of alveolar type II (ATII) pneumocytes has been decreased by NO. We tested the hypothesis that administration of the NO donor, DETANONOate, would decrease alveolar fluid clearance (AFC) in the rabbit in vivo. We instilled a solution of 5% albumin in 0.9% NaCl with 3 mM DETANONOate into anesthetized rabbits. Two hours later, similar AFC values were measured in the presence and absence of 3 mM DETANONOate (38 ± 12% versus 43 ± 13%; mean ± SD). However, animals coadministered 1 mM amiloride with one of three doses of DETANONOate (100 μ M, 300 μ M, or 3 mM) had significantly (p < 0.05) greater AFC values (23 ± 8, 20 ± 14, 28 ± 12%, respectively) than those administered amiloride alone (10 ± 7%). When 5% albumin in a Cl−-free solution was administered in the presence or absence of 100 μ M DETANONOate, neither AFC values nor alveolar Cl− concentrations were different. DETANONOate decreases the amiloride-sensitive fraction of AFC but does not decrease total AFC. DETANONOate does not influence total AFC secondary to an increase in the amiloride-insensitive fraction of AFC that is not associated with a decrease in alveolar Cl− secretion.
Sense With Cimetidine
Authors: Donald O. Castell
Journal: JAMA (1978)

Recent investigations into histamine pharmacology have shown the presence of two classes of histamine receptors analogous to the two types of receptors (a and β) for adrenergic stimulation.<sup>1</sup>These studies have resulted in the current understanding that long-known histamine effects like bronchial constriction and capillary dilation are due to stimulation of H<sub>1</sub>histamine receptors, these effects being blocked by the classical antihistaminic agents (H<sub>1</sub>receptor antagonists). Other actions of histamine, such as its ability to promote acid production from the gastric parietal cell, are now known to be due to stimulation of a distinct histamine receptor, which is designated as an H<sub>2</sub>receptor. The recent research into histamine pharmacology has resulted in the development of a series of compounds that specifically block the H2 histamine receptor.<sup>1</sup>In fact, at the annual meeting of the American Gastroenterological Association in the spring of 1974, great excitement was generated by
P3-17-10: EpCAM as a Target for Chemical Antibodies in Metastatic Breast Cancer.
Authors: SL Shigdar, W Duan
Journal: Cancer Research (2011)

Abstract EpCAM is a 40kDa glycoprotein that functions as an adhesion molecule in benign epithelium. However, it is over-expressed in nearly all carcinomas, including breast carcinomas, and has been implicated in the pathogenesis and progression of cancer. In primary breast carcinoma, its over-expression correlates with a diminished overall survival in patients with node-positive disease. Indeed, recent evidence has shown that EpCAM is expressed at a higher level in metastases than in matched primary breast carcinoma. This has led to the suggestion that EpCAM over-expression is associated with aggressive behaviour, and that it could be considered a promising therapeutic target for breast cancer. Several immunotherapy trials are ongoing, though there are limitations to their delivery and distribution, suggesting a smaller and more effective EpCAM targeting molecule is required. Aptamers, also known as chemical antibodies, are short-stranded DNA or RNA molecules and are selected via the systematic evolution of ligands by exponential enrichment (SELEX). They are 10 to 20 times smaller than antibodies and exhibit superb tissue penetration, thereby indicating their suitability in cancer targeting. In addition, aptamers are more stable, non-immunogenic and non-toxic. Following 12 rounds of SELEX using EpCAM protein as a target, we generated several EpCAM specific RNA aptamers. These were investigated using flow cytometry and confocal microscopy for their ability to bind to three breast cancer cell lines, MCF-7, T47D and MDA-MB-231. Our 19-nt aptamer showed specific binding to all three cell lines. In addition, it also showed superior penetration of breast cancer 3-D spheroid tumor models, as compared to a control aptamer and negative cell lines. This aptamer has also shown efficient internalisation via receptor-mediated endocytosis, suggesting it to be a suitable targeting moiety for drug delivery to both primary and metastatic tumors. The usefulness of this aptamer in clinical applications is being actively investigated. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-17-10.
Cost-effectiveness of ultrasound-guided liver biopsy
Authors: Tousif Pasha, Sherine Gabriel, Terry Therneau, Rolland E. Dickson, Keith D. Lindor
Journal: Hepatology (1998)

The risk of a major complication from “blind” percutaneous liver biopsy is reported to be in the range of 0.24% to 3.8%. In a recent randomized trial, patients whose liver biopsies were performed with ultrasonography had a significant reduction in complications requiring hospitalization compared with patients without ultrasound-guided biopsies (0.5% vs. 2.2%, P &lt; .05). Despite this, routine use of ultrasonography for liver biopsies has not been implemented because of controversies with respect to cost-effectiveness. The aim of our study was to analyze the relative cost-effectiveness of performing ultrasound-guided liver biopsies using decision analysis. A decision tree was constructed to compare a strategy of liver biopsy using ultrasonography with a strategy without ultrasonography. The major outcomes included were minor complications such as pain requiring analgesics and major complications, which require hospitalization. Costs included were direct medical costs from the payer’s perspective. In our baseline model, the cost from complications per patient with and without ultrasonography was $62 and $129, respectively. The marginal effectiveness expressed as the number of major complications avoided was 1.2/100 liver biopsies. The incremental cost to avoid one major complication was $2,731. The model was most sensitive to the frequency of major complications and the additional cost of ultrasonography. Our decision analysis model suggests that ultrasound-guided liver biopsy is cost-effective. Future studies assessing the efficacy of image-guided liver biopsies should be conducted.
Blockade of a Key Region in the Extracellular Domain Inhibits HER2 Dimerization and Signaling
Authors: Javier A. Menendez, Barbara Schroeder, Susan K. Peirce, Luciano Vellon, Adriana Papadimitropoulou, Ingrid Espinoza, Ruth Lupu
Journal: JNCI Journal of the National Cancer Institute (2015)

Several treatment strategies target the human epidermal growth factor receptor 2 (HER2) in breast carcinomas, including monoclonal antibodies directed against HER2's extracellular domain (ECD) and small molecule inhibitors of its tyrosine kinase activity. Yet, novel therapies are needed that prevent HER2 dimerization with other HER family members, because current treatments are only partially effective.To test the hypothesis that HER2 activation requires a protein sequence in the HER2-ECD that mediates HER2 homo- and heterodimerization, we introduced a series of deletion mutations in the third subdomain of HER2-ECD. These deletion mutants were retrovirally expressed in breast cancer (BC) cells that naturally overexpress HER2 and in noncancerous, HER2-negative breast epithelial cells. One-factor analysis of variance or Student's t test were used to analyze differences. All statistical tests were two-sided.The smallest deletion in the ECD domain of HER2, which removed only 16 amino acids (HER2-ECDΔ451-466), completely disrupted the oncogenic potential of HER2. In contrast to wild-type HER2, the mutant-inhibited anchorage-independent growth (mean number of colonies: mutant, 70, 95% confidence interval [CI] = 55 to 85; wild-type, 400, 95% CI = 320 to 480, P < .001) increased sensitivity to paclitaxel treatment in both transformed and nontransformed cells. Overexpression of HER2Δ451-466 efficiently inhibited activation of HER1, HER2, and HER3 in all cell lines tested.These findings reveal that an essential "activating" sequence exists in the extracellular domain of HER2. Disruption of this sequence disables the HER2 dimerization loop, blocks subsequent activation of HER2-driven oncogenic signaling, and generates a dominant-negative form of HER2. Reagents specifically against this molecular activation switch may represent a novel targeted approach for the management of HER2-overexpressing carcinomas.
DRUG THERAPY IN PYELITIS
Authors: HENRY F. HELMHOLZ
Journal: JAMA (1922)

The present study is concerned with an attempt to determine the direct mode of action of several of the more commonly used drugs in the treatment of pyelitis.The action of the alkalis, of hexamethylenamin and of phenyl salicylate has been studied.First, it must be said that pyelitis, in most instances, is a self limited disease, which may disappear almost as rapidly as it appears.It is sometimes discovered acci- dentally by routine examination of the urine.At other times, it may be associated with very severe symptoms, From the Section on Pediatrics, Mayo Clinic.
Abstract LB-262: Phosphatidylserine-targeting antibody synergizes with anti-PD-1 antibody to inhibit tumor growth in K1735 mouse melanoma model
Authors: Xianming Huang, dan Ye, Rolf Brekken, Yi Yin
Journal: Cancer Research (2014)

Abstract A large body of evidence indicates that PS is a major player in tumor-associated immunosuppression, including the induction and expansion of immune suppressor cells, such as MDSCs and M2 macrophages, and the production of immunosuppressive cytokines, such as TGF-beta and IL-10. Furthermore, PS also inhibits DCs maturation and antigen presentation. Thus, PS is a critical target for cancer immunotherapy. We have previously shown that anti-PS antibody can override PS-driven immunosuppression and re-program the tumor microenvironment from immunosuppressive to immunosupportive, breaks tumor immune tolerance and elicits potent de novo antitumor T-cell immunity. In the present study, we examined the combination of anti-PD-1 with anti-PS antibody in K1735 mouse melanoma model. Tumor-bearing mice were treated with each antibody alone or the combination at 2.5 mg/kg, twice a week. The combination treatment showed significantly superior tumor growth inhibition than with either antibody alone, animals treated with the combination survived significantly longer than with either antibody alone. Flow cytometry analysis showed the combination has the highest ratio of tumor-infiltrating immune effector to suppressor cells. Finally, no toxicity was observed in all treatment groups following multiple treatment doses. These data suggest that combination of PS blockade with immune checkpoint blockade represents a promising combinatorial strategy for cancer immunotherapy. Citation Format: Xianming Huang, dan Ye, Rolf Brekken, Yi Yin. Phosphatidylserine-targeting antibody synergizes with anti-PD-1 antibody to inhibit tumor growth in K1735 mouse melanoma model. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-262. doi:10.1158/1538-7445.AM2014-LB-262
A near-infrared fluorescent heptamethine indocyanine dye with preferential tumor accumulation for in vivo imaging
Authors: Chao Zhang, Tao Liu, Yongping Su, Shenglin Luo, Ying Zhu, Xu Tan, Song Fan, Lilong Zhang, Yue Zhou, Tianmin Cheng, Chunmeng Shi
Journal: Biomaterials (2010)
Improvement in quality of life with infliximab induction and maintenance therapy in patients with moderate-to-severe psoriasis: a randomized controlled trial
Authors: K. Reich, F.O. Nestle, K. Papp, J.-P. Ortonne, Y. Wu, M. Bala, R. Evans, C. Guzzo, S. Li, L.T. Dooley, C.E.M. Griffiths
Journal: British Journal of Dermatology (2006)

Background Psoriasis has a well‐documented, markedly negative effect on patient quality of life. Objectives To evaluate the impact of long‐term infliximab maintenance therapy on health‐related quality of life (HRQoL) in patients with psoriasis. Methods The Dermatology Life Quality Index (DLQI) and 36‐item Short Form Health Survey (SF‐36) were administered as part of the pivotal double‐blind, placebo‐controlled efficacy and safety EXPRESS study of infliximab in chronic plaque psoriasis. In total, 378 patients with moderate‐to‐severe psoriasis were enrolled at 32 centres in Europe and Canada. Patients were randomized to receive either placebo or infliximab 5 mg kg−1 induction at weeks 0, 2 and 6 followed by maintenance every 8 weeks; placebo patients crossed over at week 24 to receive the infliximab induction and maintenance regimen. Results At week 10, infliximab‐treated patients had significantly greater improvement in DLQI scores (P < 0·001) and SF‐36 physical and mental component summary scores (P < 0·001) than placebo‐treated patients. Significant improvement (P < 0·001) was also seen in all eight SF‐36 subscales, and was greatest for the 'Bodily Pain' and 'Social Functioning' scales. Significant improvement in HRQoL persisted with maintenance infliximab treatment at week 24 (P < 0·001), with patients achieving a Psoriasis Area and Severity Index score of 0 reporting the greatest benefit. Treatment‐related HRQoL improvement remained substantial at week 50. Conclusions Infliximab induction and maintenance regimens resulted in rapid, substantial, sustained and clinically meaningful improvement in both dermatology‐specific and general quality of life indices in patients with psoriasis, with total clearance resulting in maximum improvement.
Mass transfer rates of polycyclic aromatic hydrocarbons between micron-size particles and their environment--theoretical estimates.
Authors: P Gerde, P Scholander
Journal: Environmental Health Perspectives (1989)

This paper presents a mathematical model of how rapidly polycyclic aromatic hydrocarbons (PAHs) adsorb onto initially clean micron-size particles in the ambient air and how fast these substances are likely to be desorbed from the particles after deposition on the surface lining layer of the lung. Results show that, on the one hand, the very low gas-phase concentrations of PAHs in the ambient air should result in a comparatively slow transfer of such compounds to micron-size particles, a process that may last from minutes to hours. On the other hand, the comparatively high solubilities of PAHs in the lining layer of the lung should promote an almost instantaneous release of PAHs onto nonporous particles, and a release within a matter of minutes of most PAHs reversibly adsorbed onto the interior surfaces of porous particles. Two important conclusions can be drawn from this. First, the PAHs in tobacco smoke do not have time enough to interact in the gas phase with other airborne particles before these agents are inhaled into the smoker's lungs. Therefore, adsorption in the gas phase of PAHs onto asbestos fibers can hardly be a characteristic parameter in the mechanism behind the synergistic effect between tobacco smoking and asbestos exposure for the induction of bronchial cancer. Second, the release rate of reversibly adsorbed PAHs from their carrier particles in the lung seems to be so fast that this cannot be a parameter of importance in directly influencing the residence times of such substances in the lung.