tbuckley/cabot-search huggingface dataset:
STUDIES UPON THE EFFECT OF LIGHT ON BLOOD AND TISSUE CELLS
Authors: W. R. Earle
Journal: The Journal of Experimental Medicine (1928)

1. It was found that when hanging drops of whole blood, drawn from a rabbit, were subjected to irradiation from certain light sources, a striking degeneration of the white and of the red cells occurred. In this degeneration of the red cells there was (a) a preliminary period of 15-30 minutes during which no effect was noted; (b) following this, there was a period during which the cells swelled and became first almost biplanar, then biconvex, and finally spherical. After a spherical shape had been assumed, the liberation of blood pigment from the cells began. This process progressed with varied rapidity, sometimes being very slow, and being incomplete; sometimes being of almost explosive rapidity. This liberation was not accomplished in either case through a gross rupture of the cells, but through the agency of some submicroscopic change produced either in the cell contents, the cell wall, or both. Following this liberation of pigment, in some cultures the red cells showed signs of coagulation, as did the white cells. In other cultures, however, the red cells were reduced to achromatic shadows. 2. When whole blood was diluted with unbuffered Locke solution and then irradiated in hanging drop preparations, the erythrocytes swelled, as in whole blood, but then, instead of an almost instantaneous hemolysis of every cell present, or a slow liberation of hemoglobin from each individual cell, all the red cells hemolyzed, one or two at a time, the hemolyzed cells being left as achromatic shadows. 3. This hemolysis of the red cells, as in the case of the degeneration of the white cells, occurred upon irradiation of the culture with white light, or with light lying in each of the three spectral zones of the visual spectrum, defined by Wratten filters Nos. 45, 58 and 29 respectively, as follows: (a) 430micromicro-550micromicro; infra-red; (b) 475micromicro-630micromicro; 690micromicro-infra-red; (c) 600micromicro-infra-red. 4. Within the range of intensities of light employed, there was little or no difference in the rate at which light of these three regions acted on the red cells. Further, this rate was the same as was the rate when the red cells were irradiated with no colored filter interposed in the optical path, or when a 5 per cent total transmission neutral filter was interposed. 5. It was shown that this degeneration of the red cells under the action of light was not dependent on the presence or absence of serum, with the possible exception of that trace which might have been adherent to the red cells even after repeated washing. 6. The white cells in the culture generally showed no changes until after traces of red cell pigment could be seen free in the surrounding medium. 7. On the other hand, no neutrophils were observed moving around for longer than a few minutes after the liberation of red cell pigment had occurred. 8. The liberation of substances from the red blood cells, as a result of irradiation of such preparations, may play some major rôle in the degeneration of irradiated white cells.
Variability in the fetal hemoglobin level of the normal adult
Authors: Julia Ye. Leonova, Elena G. Kazanetz, Natalia S. Smetanina, Adekunle D. Adekile, Georgi D. Efremov, Titus H.J. Huisman
Journal: American Journal of Hematology (1996)

We analyzed blood samples from more than 200 normal adults, and quantified their Hb F by cation-exchange high-performance liquid chromatography. In several subjects with slightly elevated Hb F (0.4–4.3%), we determined the Gγ levels in the Hb F and DNA sequence variations in the locus control region II and in the Gγ and Aγ promoters. About 25% of the ∼200 normal teenaged high school students had elevated Hb F; detailed analyses of some 20 students, selected at random, identified most as females with a homozygosity for the C→T variation at position -158 (Gγ). One 11-year-old boy was heterozygous for the A→G change at position -161 (Gγ); he and two of his relatives had ∼4% Hb F, high Gγ values, and a high level of (mainly) Gγ-mRNA. Nearly 40 normal adults from Macedonia and from Georgia (mostly Caucasians) were tentatively identified as Swiss HPFH heterozygotes because slightly elevated Hb F levels were observed at least once. Many of these persons were heterozygous or homozygous for the C→T mutation at -158 (Gγ), and a few carried a γ-globin gene triplication. The C→T change appears to be an important factor predisposing the adult to increased Hb F production. Evidence suggests a gene dose effect in (mildly) anemic adults; however, other factors besides the C→T change at -158 (Gγ), including factors not linked to the β-globin region, may cause an increase in γ-chain synthesis. © 1996 Wiley-Liss, Inc.
Screening for Bacteriuria With a Test Paper for Glucose
Authors: Bengt Scherstén
Journal: JAMA (1968)

A glucose-specific test paper which is sufficiently sensitive to react with the small amounts of glucose present in urine from normal persons in the fasting state can be used to discriminate between urine samples containing more than and those containing less than 1 to 1.5 mg of glucose per 100 ml of urine. This provides a screening method for significant bacteriuria in an apparently healthy population since urine samples, obtained under standardized conditions from subjects in the fasting state with such bacteriuria, contain either very little or no glucose.
London hospital criticised for isolation facilities
Authors: M. Halle
Journal: BMJ (1996)

A report into an outbreak of drug resistant tuberculosis at a London hospital earlier this year has criticised isolation facilities.

Three patients at St Thomas's Hospital were infected by a woman with the disease and two died. An independent inquiry into the outbreak, released last week, says that there was a problem of communication among staff about infection control and a lack of suitable isolation rooms for the care of highly infectious patients. An investigation …
Framing the research agenda for sickle cell trait: Building on the current understanding of clinical events and their potential implications
Authors: Jonathan C. Goldsmith, Vence L. Bonham, Clinton H. Joiner, Gregory J. Kato, Allan S. Noonan, Martin H. Steinberg
Journal: American Journal of Hematology (2011)

Sickle Cell Trait (HbAS), the heterozygous state for the sickle hemoglobin beta globin gene is carried by as many as 100 million individuals including up to 25% of the population in some regions of the world (World Health Organization, Provisional agenda item 4.8, EB117/34 (22 December 2005) or World Health Organization, Provisional agenda item 11.4 (24 April 2006)). Persons with HbAS have some resistance to falciparum malaria infection in early childhood (Piel FB, Patil AP, Howes RE, et al., Nat Commun 2010;1104:1-7 and Aidoo M, Terlouw DJ, Kolczak M, et al., Lancet 2002;359:1311-1312) and as a result individuals with HbAS living in malarial endemic regions of Africa have a survival advantage over individuals with HbAA. Reports from the US emphasize possible health risks for individuals with HbAS including increased incidence of renal failure and malignancy, thromboembolic disorders, splenic infarction as a high altitude complication, and exercise-related sudden death. The National Heart, Lung, and Blood Institute, National Institutes of Health convened a workshop in Bethesda, Maryland on June 3-4, 2010, Framing the Research Agenda for Sickle Cell Trait, to review the clinical manifestations of HbAS, discuss the exercise-related sudden death reports in HbAS, and examine the public health, societal, and ethical implications of policies regarding HbAS. The goal of the workshop was to identify potential research questions to address knowledge gaps.
Walk-in clinics at US retail outlets run into financial problems
Authors: Fred Charatan
Journal: BMJ (2008)

Patients who have confounded doctors with signs and symptoms that elude diagnosis are to be offered the expertise of hundreds of doctors in a unique programme from the US National Institutes of Health."Physicians deal with about 6600 conditions and 6000 of them are quite rare.Even common diseases have many subtypes," the institutes' director Elias A Zerhouni said during a telephone news conference with reporters earlier this week.He said it was not surprising that many can go undiagnosed for years.The programme aims to combine the revolution in tools and information at the molecular level with the expertise of the 1600 doctors at the NIH Clinical Center "to assist patients around the country and their doctors."It will add to the knowledge base by creating a phenotype atlas of disease."We are doing this now because of the advances that have been made over the last five years at the fundamental level.We have many more biologic markers, the significance of which is not always understood." Dr Zerhouni said that for the first time his organisation was going to apply these sophisticated laboratory tests to human diseases on a large scale.Under the current system of research at the NIH Clinical Center, patients with challenging conditions "are triaged to a specific institute or protocol programme, and are assessed by one team," said John I Gallin, director of the centre.Participants in the new programme "will be assessed by a large spectrum of teams."Candidate patients must be referred by a healthcare provider and will have to submit exhaustive medical records that will be reviewed by a multidisciplinary team of 25 senior doctors.Those who are accepted into the programme will travel to the centre for an evaluation, which is likely to take at least a week.Details are available at http://rarediseases.info.nih.gov/
The Pieces of a Vitamin D Puzzle Fall into Place — Almost!
Authors: Donald R. Wright
Journal: New England Journal of Medicine (1975)

One of the more rapidly advancing fields of medical research at present relates to the metabolism of vitamin D and to its mechanisms of action in mineral-ion homeostasis. The outline of this fascinating story will not be retold in detail here, but one of the major investigators in this field has recently written a very readable and comprehensive review for clinicians.1 Briefly, it is now clear that vitamin D, once absorbed in the gut or formed in the skin by ultraviolet irradiation, must undergo 25-hydroxylation in the liver and then 1α-hydroxylation in the kidney before it becomes biologically active under . . .
Postpneumonectomy empyema: drainage by spontaneous oesophagopleural fistula.
Authors: H Holdt, S Liebig, A Gabler
Journal: Thorax (1983)

Oesophagopleural fistula after pneumonectomy is not as uncommon as the 49 previously published cases might sug- gest.Nevertheless, it presents a diffidlt therapeutic prob- lem.Direct surgical repair of the fistula is the treatment of choice'-7 as the mortality rate approaches 100% in patients who are not fit for surgery.This report describes the case of a patient who survived without surgical treat- ment as the fistula provided effective drainage of the empyema space.
De subitaneis mortibus. XXVIII. Apoplexy of the heart.
Authors: T N James
Journal: Circulation (1978)

Apoplexy of the heart can be responsible for sudden and for recurring instability of cardiac rhythm and conduction, and for the clinical counterparts of syncope and sudden death. Every pathophysiological mechanism which produces cerebral apoplexy has its counterpart in apoplexy of the heart. Among the mechanisms documented are thrombosis, embolism and rupture of those special vessels supplying the sinus node, atrioventicular (A-V) node and His bundle. Apoplexy of the heart can occur either with or without significant or recognizable ventricular myocardial infarction. Acute vascular accidents within the critical centers of cardiac impulse formation and conduction deserve more frequent consideration in the explanation of unusual cases of "epilepsy", of seizure disorders of the elderly, of neurologic manifestations (which may be secondary as well as primary) of systemic diseases such as lupus erythematosus or thrombotic thrombocytopenic purpura, and indeed of every case of otherwise unexplanined syncope or sudded death at any age.
Middle East Cancer Consortium Stays on Track to Collect Data
Authors: Aaron Levin
Journal: JNCI Journal of the National Cancer Institute (1998)

With the regulatory changes, FDA can require drug companies to conduct additional clinical trials to provide prescribing information specifically for children.In exchange, the drug company would receive an additional 6 months of marketing exclusivity.For drugs that are already off-patent, there is little incentive for drug companies to invest in additional pediatric research.Into that gap steps the National Institute of Child Health and Human Development, which will use a grant from the American Medical Association for pediatric pharmacology research.According to Alexander, only five of the 80 drugs used most frequently in newborns and infants have pediatric use instructions.NICHD's research will focus on drugs that are offpatent and frequently prescribed without specific pediatric labeling.
Abstract P6-11-02: Inhibition of mTOR and Fatty Acid Synthase (FASN) overcome acquired resistance to Trastuzumab, Lapatinib and both in HER2+ breast cancer
Authors: T Puig, A Blancafort, A Giro, A Viqueira, G Viñas, A Massaguer, D Carrion-Salip, MV Bolos, A Urruticoechea, G Oliveras
Journal: Cancer Research (2012)

Abstract Introduction: Resistance to dual biological blockade of HER2 positive breast cancer arises as a novel therapeutic challenge with high clinical relevance. We have shown that inhibition of fatty acid synthase (FASN) has anticancer activity and enhances the effect of chemotherapy and anti-HER2 drugs in pre-clinical breast cancer models. Furthermore, our group has recently observed that inhibition of FASN can reverse resistance to anti-HER2 therapies. The development of FASN inhibitors has consequently appeared as a novel anti-target modality for treating cancer. However, the clinical use of FASN inhibitors, such as Cerulenin, C75 and Epigallocatechin 3-gallate (EGCG) is limited by anorexia and induced body weight loss or by its low in vivo potency and stability. We synthesized novel EGCG-related inhibitors to improve their use as anti-tumor agents. Within these, G28UCM was selected for its inhibitory effect of FASN activity and selective cytotoxicity in tumor cells. Recently, it has been reported that mTOR blockade acts synergistically with HER2 inhibition to induce cell death and tumor regression in resistant breast cancer models. Materials and Methods: We have developed long term HER2+/ FASN+ breast cancer cell lines (SKBr3) resistant to the HER2-monoclonal antibody Trastuzumab (SKTR), the EGFR/HER2-tyrosine kinase inhibitor Lapatinib (SKLR) or both (SKLTR). Once established, we have characterized these cells by studying a panel of EGF receptors signaling proteins with western blot analysis, changes in adherence to extracellular matrix proteins and invasion capacity with colorimetric assays. Using MTT assay, we have assessed the effect of the mTOR-inhibitor, Temsirolimus, and G28UCM on viability of parental and resistant cells. The isobologram method has been used to estimate the possible synergistic effect between both treatments. Results: Resistant cells maintained downstream HER2 pathway activation by stimulating the expression/activation of alternative EGF family receptors and/or those specific ligands. Moreover, these cells increased adherence to extracellular matrix proteins and invasion capacity. Different combination regiment of Temsirolimus with G28UCM displayed a strong synergistic effect in inducing cell death of both, parental and resistant HER2+ breast cancer cells. Conclusions: The inhibition of mTOR and FASN is a potential novel therapeutic strategy in dual resistant HER2 positive breast cancer. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-11-02.
Models of Mental Health Training in Primary Care
Authors: Harold Alan Pincus, James J. Strain, Jeffrey L. Houpt, Leslie H. Gise
Journal: JAMA (1983)

THE EVOLUTION of health policy and clinical science has had a substantial influence in recent decades on the relationship between mental health and general health. Federal initiatives encouraging linkages between community mental health centers and community health centers, the growth of Health Maintenance Organizations and other organized care settings, health manpower legislation with a mandate for primary care, and advances in biologic psychiatry and behavioral medicine all have contributed to the movement of mental health into the mainstream of health services. Evidence of the developing relationship is seen in analyses of the de facto mental health and health service systems. Recent data by Regier et al<sup>1</sup>indicate that of the estimated 35 million persons in the United States who suffer a diagnosable mental disorder annually, approximately 54% are seen exclusively in the general health care sector. Moreover, between 15% and 50% of all patients visiting primary care physicians have
Empathy or imperturbability?
Authors: J. Smith
Journal: BMJ (2012)

In this week’s BMJ Daniel Sokol, following Osler, commends imperturbability as an essential quality for a doctor (doi:10.1136/bmj.e3980). He advocates the “outward calm, a reassuring coolness” that inspires confidence in patients. And he contrasts it with empathy—“doctors crying in front of patients, praying with them, or displaying outward effusions of emotion.”

Both empathy and imperturbability are reflected in articles we publish this week on assisted dying, suggesting that both qualities have their place. Tess McPherson’s Personal View (doi:10.1136/bmj.e4007) about her mother’s death appeals for an empathic response: would you want to die like that? But Raymond Tallis argues that doctors’ organisations should stand back from the debate about assisted dying and …
ME-18 * INDUCTION OF M2 TYPE MACROPHAGES BY GBM CELLS
Authors: A. Rodriguez, D. Gibo, W. Debinski
Journal: Neuro-Oncology (2014)

Tumor associated macrophages (TAMS) have many roles in the tumor microenvironment. TAMs aid in pro-tumor mechanisms, such as invasion, migration, tumor proliferation, angiogenesis, and immunosupression. The predominant phenotype of TAMs is an M2 or anti-inflammatory phenotype. We utilized an in vitro culture system to investigate GBM cells' induction of M2 polarization in macrophages. THP-1 cells, a human monocytic cell line, were grown in conditioned media from three different GBM cell lines: G48, BTCOE 4795, and BTCOE 4536; the latter two are low passage explant cells. M2 activation markers (CD163, CD163L1, CD204, and CD206) and cytokine secretion profiles were assayed via immunoblotting and cytokine arrays respectively. The conditioned media of all GBM cell induced CD163, CD163L1, and CD204 expression in THP-1 cells. They also expressed prominently MCP-1, TNF-α, IL-3, GM-CSF, IL-8, GRO, IL-10, oncostatin and RANTES. These phenotypic characteristics were similar to our M2 positive controls which were monocytes induced by the classical anti-inflammatory paradigm, phorbol myristate acetate (PMA), IL-4, and IL-13. To further investigate how monocytes were polarized to M2 macrophages by GBM cells, we analyzed the secretomes of all three GBM cell lines using mass spectrometry. We have identified several candidates that play a role in macrophage recruitment and activation. Among a number of such factors, CCL-2 was a candidate protein identified by our proteomic analysis. We have been able to demonstrate M2 activation by CCL-2 in our in vitro monocyte cultures in follow up studies. These results indicate that GBM cells are able to induce monocytes to become M2 macrophages by a direct cross-communication. Further elucidation and understanding of these complex interactions should lead to developing novel therapies to circumvent TAMs pro-tumor mechanisms in the GBM microenvironment.
A COMPARISON BETWEEN 9a-FLUOROHYDROCORTISONE AND HYDROCORTISONE IN THE TOPICAL TREATMENT OF CERTAIN DERMATOSES.
Authors: BENJAMIN PORTNOY
Journal: British Journal of Dermatology (1956)

Journal Article A COMPARISON BETWEEN 9a‐FLUOROHYDROCORTISONE AND HYDROCORTISONE IN THE TOPICAL TREATMENT OF CERTAIN DERMATOSES. Get access BENJAMIN PORTNOY BENJAMIN PORTNOY Physician, Manchester and Salford Hospital for Skin Diseases Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 68, Issue 9, 1 September 1956, Pages 303–306, https://doi.org/10.1111/j.1365-2133.1956.tb12823.x Published: 01 September 1956
Cell growth and differentiation of a novel mouse Ito (fat-storing) cell line transformed by a temperature-sensitive mutant of simian virus 40
Authors: Y Kitamura, T Tanigawa, T Katsumoto, K Tomita, H Wang, K Hirai, K Ichihara, T Terada
Journal: Hepatology (1997)

A novel mouse Ito (fat-storing) cell line (A640-IS) was established by transformation with a temperature-sensitive mutant of simian virus 40 (SV40) and the relationships between the expression of SV40 large T antigen and the growth, differentiation, and functions of A640-IS cells were investigated. A640-IS cells expressed large T antigen when cultured at 33 degrees C. At this temperature, the cells grew actively, assumed a fibroblastic shape, and showed few Ito cell characteristics. In contrast, when large T-antigen expression was inhibited by culture at 39 degrees C, the cells did not grow but differentiated into Ito cells as assessed by both morphological and functional characteristics. Expression of the transcription factor SCL (stem cell leukemia), which plays a role in the development and differentiation of blood cells, was observed at both 33 degrees C and 39 degrees C, although expression was greater at 33 degrees C. Therefore, opposite patterns of cell growth and the functions of differentiated cells occurred at 33 degrees C and 39 degrees C in this novel Ito cell line. Transforming growth factor beta1 stimulated A640-IS cells to produce fibronectin, collagen type III, and laminin. This unique Ito cell line provides a useful model to address important questions regarding the nature of these cells.
Stabilization of the bioactivity of tumor necrosis factor by its soluble receptors.
Authors: D Aderka, H Engelmann, Y Maor, C Brakebusch, D Wallach
Journal: The Journal of Experimental Medicine (1992)

The receptors for tumor necrosis factor (TNF) exist in cell-associated as well as soluble forms, both binding specifically to TNF. Since the soluble forms of TNF receptors (sTNF-Rs) can compete with the cell-associated TNF receptors for TNF, it was suggested that they function as inhibitors of TNF activity; at high concentrations, the sTNF-Rs indeed inhibit TNF effects. However, we report here that in the presence of low concentrations of the sTNF-Rs, effects of TNF whose induction depend on prolonged treatment with this cytokine are augmented, reflecting an attenuation by the sTNF-Rs of spontaneous TNF activity decay. Evidence that this stabilization of TNF activity by the sTNF-Rs follows from stabilization of TNF structure within the complexes that TNF forms with the sTNF-Rs is presented here, suggesting that the sTNF-Rs can affect TNF activity not only by interfering with its binding to cells but also by stabilizing its structure and preserving its activity, thus augmenting some of its effects.
The use of antibody modified liposomes loaded with AMO-1 to deliver oligonucleotides to ischemic myocardium for arrhythmia therapy
Authors: Meifang Liu, Minghui Li, Shouli Sun, Baoxin Li, Dan Du, Jialiang Sun, Fangyuan Cao, Haichun Li, Feng Jia, Tianfu Wang, Naidan Chang, Hui Yu, Qun Wang, Haisheng Peng
Journal: Biomaterials (2014)