tbuckley/cabot-search huggingface dataset:
Human monocyte interaction with antibody‐coated platelets. I. General characteristics
Authors: Wayne S. Court, A. Kent Christensen, Roger W. Sacks, Albert F. Lobuglio
Journal: American Journal of Hematology (1984)

Abstract The interaction of human monocytes with antibody‐coated and normal platelets was studied using an assay system that employed rate zonal centrifugation to separate monocyte‐associated (bound) platelets from free platelets. At a monocyte:platelet ratio of 1:10, monocytes bound 21.2 ± 6.6% of antibody‐coated platelets and less than 2.2 ± 1.3% of control platelets. Monocyte binding of antibody‐coated platelets was rapid and inhibited by monomeric IgG and staphylococcal protein A. Specific binding was positively related to the number of monocytes present and the amount of IgG displayed on the platelet surface. Transmission and scanning electron micrographs illustrate the membrane binding of antibody‐coated platelets to monocytes and suggest that phagocytosis of platelet targets occurs as well. Thus, these observations indicate that monocytes can participate in Fc‐receptor binding of anti‐PL A1 ‐sensitized platelets. This novel assay may be useful in the analysis of monocyte‐macrophage Fc‐receptor interaction with platelets sensitized with IgG from both iso‐ and autoimmune disorders as well as in the characterization of treatment modalities which may alter monocyte Fc‐receptor recognition and binding.
Defending the Con Side: Obesity Paradox Does Not Exist
Authors: Eberhard Standl, Michael Erbach, Oliver Schnell
Journal: Diabetes Care (2013)

The elegant review of Hainer and Aldhoon-Hainerova, “Obesity Paradox Does Exist” (1), rightly points out that the so-called reverse epidemiology of a better outcome associated with obesity occurs only in patients with established cardiovascular (CV) disease (CVD) including heart failure (refs. 1–35 in the review by Hainer and Aldhoon-Hainerova (1). At the primary prevention level, however, studying large cohorts, e.g., the population of 359,387 participants recruited in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study with a follow-up of 9.7 years (2), increased waist circumference as a surrogate of obesity clearly was a strong predictor of increased mortality, and there are numerous similar studies confirming the primary importance of obesity in the context of a higher total mortality or CV morbidity and mortality, as discussed further in this article. This notion has not been challenged in the article of Hainer and Aldhoon-Hainerova (1).

Furthermore, it has to be kept in mind that epidemiology never proves causality, even it is reverse and contrary to the expectation. Indeed, there may be many reasons why this reverse epidemiology may be seen in patients with CVD, including selection bias, treatment bias, distinct phenotypes of CVD patients including weight differences and differences in prognosis, a multitude of comorbidities and confounders, and last but not least, anabolic deficiency or the malnutrition-inflammation syndrome. This article attempts to address all of these important issues and, in the last part, also evaluates the beneficial effects of weight loss in prospective long-term studies on overall mortality, CV morbidity and mortality, and type 2 diabetes. Randomized controlled trials (RCTs) are thought to provide the top class of scientific evidence as well as the strongest recommendations for therapy. Most RCTs on weight loss and CV benefit, however, are still ongoing, and only a few have reported outcomes to date. …
Direct and differential effects of stem cell factor on the neovascularization activity of endothelial progenitor cells
Authors: Koung Li Kim, Yongsun Meng, Ji Yeon Kim, Eun Jung Baek, Wonhee Suh
Journal: Cardiovascular Research (2011)

Previous studies on the role of stem cell factor (SCF) in endothelial progenitor cell (EPC)-mediated neovascularization have focused on the EPC mobilization and homing process. However, the direct effects of SCF on neovascularization activity of EPCs have not been characterized. We sought to determine whether SCF regulates the neovascularization ability of EPCs by comparing its roles in mature endothelial cells.In vitro and in vivo assays revealed that SCF substantially increased the neovascularization activity of human EPCs through the c-Kit receptor. Notably, the SCF-induced increase in neovascularization activity was substantially greater in EPCs than that in human umbilical vein endothelial cells (HUVECs). SCF-induced phosphorylation of c-Kit and downstream signalling molecules was consistently found to be more potent and longer-lasting in EPCs than in HUVECs. This high responsiveness of EPCs to SCF was explained by the finding that the cell-surface expression of c-Kit is far higher in EPCs than in HUVECs. A c-Kit promoter assay revealed that the increased expression of c-Kit in EPCs could be attributed to the greater expression of stem cell leukaemia, LIM-only 2, and GATA-binding protein 2.In addition to its documented role in the mobilization and recruitment of EPCs, our findings show that SCF directly enhances the neovascularization activity of EPCs. Furthermore, the present study provides further evidence that EPCs exhibit differentially greater responsiveness to hypoxia-inducible cytokines, including SCF, than mature endothelial cells, suggesting that EPCs in ischaemic tissues function differently from mature endothelial cells, although they exhibit very similar phenotypes.
The effects of maternal exercise on developing rat fetuses.
Authors: M. Mottola, K. M. Bagnall, K. D. McFadden
Journal: British Journal of Sports Medicine (1983)

Ten female Sprague-Dawley rats (45.3 days old, s.d. = 3.9) were acclimatised to running on a treadmill at 20 m/min on a 10 degrees incline for 1 hour per day. After mating, one rat from each of 5 pairs continued running on the treadmill at 15 m/min on a 10 degrees incline for 1 hour per day throughout gestation whilst the other rats followed normal laboratory routine. All the rats were weighed daily and at birth the number and weights of all fetuses were measured. In addition, a small piece of diaphragmatic muscle was taken from each of three fetuses from each litter and assessed both histologically and histochemically. The results showed that the maternal rats that did not continue exercising throughout pregnancy produced, on average, approximately 3 more fetuses per litter than the rats that exercised, although this difference was not significant. There was also no difference in mean fetal weight between the two groups and no difference could be demonstrated in the development of the diaphragm muscle.
Cardiac Resuscitation and Neurologic Tolerance to Anoxia
Authors: RAYMOND C. READ, C. WALTON LILLEHEI, RICHARD L. VARCO
Journal: Circulation Research (1956)

Complete inflow stasis of the heart was associated with less central nervous system damage, if the heart was resuscitated with massage. Ventricular fibrillation did not occur during the period of circulatory arrest, but it was seen occasionally after the heart filled. Its incidence was increased by the use of Adrenalin and by allowing the heart to recover without massage. The administration of various doses of heparin had no effect on the Degrees of brain damage resulting from interruption of the circulation.
Recombinant human transforming growth factor-alpha stimulates the formation of osteoclast-like cells in long-term human marrow cultures.
Authors: N Takahashi, B R MacDonald, J Hon, M E Winkler, R Derynck, G R Mundy, G D Roodman
Journal: Journal of Clinical Investigation (1986)

Transforming growth factor-alpha (TGF-alpha) is synthesized by a variety of tumor cell lines and stimulates osteoclastic bone resorption in vitro. The mechanism by which TGF-alpha increases osteoclast activity is unknown. We used a human marrow culture system that forms osteoclast-like multinucleated cells (MNCs) to determine the effects of recombinant human TGF-alpha on MNC formation. Addition of 0.01 ng/ml TGF-alpha for the 1st week followed by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] for the subsequent 2 wk significantly increased MNCs. Treatment of these cultures with TGF-alpha without later addition of 1,25(OH)2D3 did not increase MNC formation. Autoradiographic studies revealed that TGF-alpha stimulated proliferation of precursors for MNCs, and 1,25(OH)2D3 increased their rate of fusion into MNCs. Addition of murine epidermal growth factor (EGF) (0.1 ng/ml) followed by 1,25(OH)2D3 also significantly stimulated MNC formation. These data suggest that TGF-alpha and EGF may stimulate bone resorption by increasing the proliferation of osteoclast precursors, which leads to increased numbers of osteoclasts.
Chromogranin A in children with neuroblastoma. Serum concentration parallels disease stage and predicts survival.
Authors: R J Hsiao, R C Seeger, A L Yu, D T O'Connor
Journal: Journal of Clinical Investigation (1990)

Chromogranin A is an acidic protein costored and coreleased with catecholamines from storage vesicles. Its serum concentration is elevated in patients with peptide-producing endocrine neoplasia. We measured serum chromogranin A at the time of diagnosis in 34 children with all stages of neuroblastoma. With a sensitivity of 91% and specificity of 100%, serum chromogranin A emerged as a useful diagnostic tool for neuroblastoma, comparable to or better than other measurements such as neuron-specific enolase, ferritin, or dopamine-beta-hydroxylase. Mean serum chromogranin A correlated with disease stage (r = 0.76, P less than 0.01). The relationship of prognosis (progression-free survival) to baseline serum chromogranin A, age, and disease stage was determined in 34 patients at risk for relapse, with a median followup period of 18 mo (range, 1-48 mo). The survival rate for patients with lower serum chromogranin A levels (less than 190 ng/ml at the time of diagnosis) was 69%, whereas it was 30% for those with higher chromogranin A levels (P less than 0.05). Furthermore, when subjects were additionally stratified by either age or stage, chromogranin A was an effective prognostic tool in patients who either were older than 1 yr (P less than 0.005) or had more advanced disease (stage III or IV; P less than 0.05). We conclude that serum chromogranin A in neuroblastoma is (a) a valuable (sensitive and specific) diagnostic tool, (b) a correlate of tumor burden, and (c) a useful predictor of survival.
MUC1 Oncoprotein Regulates Bcr-Abl Stability and Pathogenesis in Chronic Myelogenous Leukemia Cells
Authors: Takeshi Kawano, Masaki Ito, Deepak Raina, Zekui Wu, Jacalyn Rosenblatt, David Avigan, Richard Stone, Donald Kufe
Journal: Cancer Research (2007)

Abstract Chronic myelogenous leukemia (CML) results from expression of the Bcr-Abl fusion protein in hematopoietic stem cells. The MUC1 heterodimeric protein is aberrantly overexpressed in diverse human carcinomas. The present studies show that MUC1 is expressed in the human K562 and KU812 CML cell lines. The results show that MUC1 associates with Bcr-Abl through a direct interaction between the Bcr N-terminal region and the MUC1 cytoplasmic domain. Stable silencing of MUC1 decreased cytoplasmic Bcr-Abl levels by promoting Bcr-Abl degradation. Silencing MUC1 was also associated with decreases in K562 and KU812 cell self-renewal capacity and with a more differentiated erythroid phenotype. The results further show that silencing MUC1 increases sensitivity of CML cells to imatinib-induced apoptosis. Analysis of primary CML blasts confirmed that, as found with the CML cell lines, MUC1 blocks differentiation and the apoptotic response to imatinib treatment. These findings indicate that MUC1 stabilizes Bcr-Abl and contributes to the pathogenesis of CML cells by promoting self renewal and inhibiting differentiation and apoptosis. [Cancer Res 2007;67(24):11576–84]
STUDIES ON THE PHYSIOLOGICAL CONDITIONS PREVAILING IN TISSUE CULTURES
Authors: Hans Zinsser, Emanuel B. Schoenbach
Journal: The Journal of Experimental Medicine (1937)

An analysis of some of the physiological factors active in Maitland tissue cultures has been presented in the hope that it may be of some value in clarifying the principles underlying tissue cultures in general. It has been found that the empirically determined necessity of using relatively small amounts of tissue in such cultures is dependent upon the fact that excessive tissue leads to a rapid change of reaction toward the acid side. Whereas tissue may remain viable in an environment as alkaline as pH 9 and over, viability is rapidly destroyed when the reaction approaches pH 6. Evidence is presented to indicate that the changes in electrode potentials which take place in Maitland cultures are not, as has been suggested, the determining factors upon which virus multiplication depends, although they may, of course, be incidentally important. It has been shown that there are fundamental differences between those conditions in Maitland cultures which favor the multiplication of a typical virus and those upon which the growth of the Rickettsiae of typhus fever depends. The virus which we have studied (equine encephalitis virus, western type) multiplies during the period of active tissue metabolism. The maximum virus titrations are obtained at about the time at which metabolism has come to a standstill. Thereafter the virus not only ceases to increase but rapidly deteriorates. The period of viability of the tissue cells themselves is shortened by several days in the presence of virus multiplication. There is some evidence that a temporary acceleration of oxygen uptake takes place during the time of active virus multiplication. Technical difficulties in controlling such experiments prevent certainty in regard to this point. In contrast with the conditions determining the growth of a virus agent in the Maitland cultures the multiplication of Rickettsiae does not begin to any determinable extent until after active cell metabolism has either become stabilized or has ceased. The Rickettsiae continue to grow at a time when the cells are no longer viable. It appears likely that these organisms find the most favorable conditions for growth in cells which are no longer metabolically active but in which some delicately heat-susceptible elements have not yet been disturbed. As a consequence of these observations, frozen and preserved embryonic tissues have been successfully used for Rickettsia cultivation. A report on these experiments will be made in a separate communication.
Two-Year Prevalence and Stability of Individual DSM-IV Criteria for Schizotypal, Borderline, Avoidant, and Obsessive-Compulsive Personality Disorders: Toward a Hybrid Model of Axis II Disorders
Authors: Thomas H. McGlashan, Carlos M. Grilo, Charles A. Sanislow, Elizabeth Ralevski, Leslie C. Morey, John G. Gunderson, Andrew E. Skodol, M. Tracie Shea, Mary C. Zanarini, Donna Bender, Robert L. Stout, Shirley Yen, Maria Pagano
Journal: American Journal of Psychiatry (2005)

This study tracked the individual criteria of four DSM-IV personality disorders-borderline, schizotypal, avoidant, and obsessive-compulsive personality disorders-and how they change over 2 years. This clinical sample of patients with personality disorders was derived from the Collaborative Longitudinal Personality Disorders Study and included all participants with borderline, schizotypal, avoidant, or obsessive-compulsive personality disorder for whom complete 24-month blind follow-up assessments were obtained (N=474). The authors identified and rank-ordered criteria for each of the four personality disorders by their variation in prevalence and changeability (remission) over time. The most prevalent and least changeable criteria over 2 years were paranoid ideation and unusual experiences for schizotypal personality disorder, affective instability and anger for borderline personality disorder, feeling inadequate and feeling socially inept for avoidant personality disorder, and rigidity and problems delegating for obsessive-compulsive personality disorder. The least prevalent and most changeable criteria were odd behavior and constricted affect for schizotypal personality disorder, self-injury and behaviors defending against abandonment for borderline personality disorder, avoiding jobs that are interpersonal and avoiding potentially embarrassing situations for avoidant personality disorder, and miserly behaviors and strict moral behaviors for obsessive-compulsive personality disorder. These patterns highlight that within personality disorders the relatively fixed criteria are more trait-like and attitudinal, whereas the relatively intermittent criteria are more behavioral and reactive. These patterns suggest that personality disorders are hybrids of traits and symptomatic behaviors and that the interaction of these elements over time helps determine diagnostic stability. These patterns may also inform criterion selection for DSM-V.
Empirical Validation of Guidelines for the Management of Pharyngitis in Children and Adults
Authors: Warren J. McIsaac
Journal: JAMA (2004)

Recent guidelines for management of pharyngitis vary in their recommendations concerning empirical antibiotic treatment and the need for laboratory confirmation of group A streptococcus (GAS).To assess the impact of guideline recommendations and alternative approaches on identification and treatment of GAS pharyngitis in children and adults.Throat cultures and rapid antigen tests were performed on 787 children and adults aged 3 to 69 years with acute sore throat attending a family medicine clinic in Calgary, Alberta, from September 1999 to August 2002. Recommendations from 2 guidelines (those of the Infectious Diseases Society of America and of the American College of Physicians-American Society of Internal Medicine/American Academy of Family Physicians/US Centers for Disease Control and Prevention) were compared with rapid testing alone, a clinical prediction rule (ie, the modified Centor score), and a criterion standard of treatment for positive throat culture results only.Sensitivity and specificity of each strategy for identifying GAS pharyngitis, total antibiotics recommended, and unnecessary antibiotic prescriptions.In children, sensitivity for streptococcal infection ranged from 85.8% (133/155; 95% confidence interval [CI], 79.3%-90.0%) for rapid testing to 100% for culturing all. In adults, sensitivity ranged from 76.7% (56/73; 95% CI, 65.4%-85.8%) for rapid testing without culture confirmation of negative results to 100% for culturing all. In children, specificity ranged from 90.3% (270/299; 95% CI, 86.4%-93.4%) for use of modified Centor score and throat culture to 100% for culturing all. In adults, specificity ranged from 43.8% (114/260; 95% CI, 37.7%-50.1%) for empirical treatment based on a modified Centor score of 3 or 4 to 100% for culturing all. Total antibiotic prescriptions were lowest with rapid testing (24.7% [194/787]; 95% CI, 21.7%-27.8%) and highest with empirical treatment of high-risk adults (45.7% [360/787]; 95% CI, 42.2%-49.3%), due to a high rate of unnecessary prescriptions in adults (43.8% [146/333]; 95% CI, 38.4%-49.4%).Guideline recommendations for the selective use of throat cultures but antibiotic treatment based only on positive rapid test or throat culture results can reduce unnecessary use of antibiotics for treatment of pharyngitis. However, empirical treatment of adults having a Centor score of 3 or 4 is associated with a high rate of unnecessary antibiotic use. In children, strategies incorporating throat culture or throat culture confirmation of negative rapid antigen test results are highly sensitive and specific. Throat culture of all adults or those selected on the basis of a clinical prediction rule had the highest sensitivity and specificity.
Multidirectional clinical profile (MDCP) for the functional GI disorders: first edition
Authors: Shaheen Hamdy
Journal: Gut (2015)

Dr Douglas A Drossman MD, Editor, with contributions from Fernando Azpiroz, Lin Chang, William D Chey, Douglas A Drossman, John Kellow, Max J Schmulson, Magnus Simren, Robin Spiller, Jan Tack, William E Whitehead

There is a well-established opinion among gastroenterologists from all nations that functional GI disorders and irritable bowel syndrome are the most common diagnoses made in GI clinics and yet represent some of the most challenging patients to manage. The medical mind set is to establish a diagnosis through history, examination and diagnostic tests and to come up with a clear organic explanation for GI disorders. Unfortunately in functional GI disorders, this pathway is often fraught with pitfalls and difficulties and frequently results in endless investigations and fruitless end outcomes for patients in whom no clear organic pathology can be found. Despite all this, it has been known for centuries that there exist people who present with disturbance of gut function without explanation. Such patients remained somewhat of an enigma in those times, but we would now recognise them as having functional GI disorders such as irritable bowel syndrome.1

In order to attempt to better characterise and indeed provide better …
Abstract SY43-02: Mismatch repair, gut microbiota, and the etiology of colon cancer
Authors: Alberto Martin
Journal: Cancer Research (2015)

Abstract The etiology of colorectal cancer (CRC) has been linked to deficiencies in mismatch repair and adenomatous polyposis coli (APC) proteins, diet, inflammatory processes, and gut microbiota. However, the mechanism through which the microbiota synergizes with these etiologic factors to promote CRC is not clear. We report that altering the microbiota composition reduces CRC in APC(Min/+)Msh2-/- and APC(Min/+)Mlh1-/- mice, and that a diet reduced in carbohydrates phenocopies this effect. Gut microbes did not induce CRC in these mice through an inflammatory response or the production of DNA mutagens but rather by providing carbohydrate-derived metabolites such as butyrate that fuels hyperproliferation of Msh2-/- and Mlh1-/- colon epithelial cells. Further, we provide evidence that the mismatch repair pathway has a role in regulating β-catenin activity and potentially modulating the differentiation of transit-amplifying cells in the colon. These data show that mismatch repair deficiency sensitizes colon epithelial cells to transformation by gut microbiota, and thereby provide an explanation for the interaction between microbiota, diet, and mismatch repair deficiency in CRC induction. Citation Format: Alberto Martin. Mismatch repair, gut microbiota, and the etiology of colon cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr SY43-02. doi:10.1158/1538-7445.AM2015-SY43-02