tbuckley/cabot-search huggingface dataset:
The different faces of myelodysplasia in peripheral blood granulocytes
Authors: Meir Preis, Deborah L. Ornstein
Journal: American Journal of Hematology (2013)

A 75 year-old woman presented with fevers, night sweats and weight loss four months after completing a course of adjuvant chemotherapy for ovarian cancer. A CBC showed normocytic anemia (hemoglobin 56 g/L), thrombocytopenia (34 × 109/L) and leukocytosis (16.6 × 109/L) with a granulocyte left-shift and 11% blasts. The peripheral blood findings seen in this patient illustrate the different manifestations of myelodysplasia in the granulocytes: cells with ring nuclei (Figure 1, panels A and B), christened “donut cells”; cells with abnormal cytoplasmic granules (pseudo Chediak-Higashi granules; panel C), and bi-lobed nuclei (pseudo Pelger-Huet cells; panel D and panel E, arrow). Platelets were large and agranular (panel D, arrow) which are also part of the underlying dysplasia. Nucleated RBCs were also present in the peripheral blood suggesting trilineage dysplasia (panel F). The bone marrow was hypercellular with trilineage dysplasia and 22% myeloblasts with a complex karyotype (including del-5q and del-7). 1 She was treated with four cycles of decitabine, resulting in resolution of fevers, eradication of bone marrow blasts, and restoration of normal hematopoiesis.2 Evidence for a salutary effect of the hypomethylating agent in this patient was seen also by restoration of normal peripheral blood cells morphology (panels G–I). This case illustrates several unique morphological changes in dysplastic granulocytes on a peripheral blood smear in one patient with secondary acute myeloid leukemia.
Is it time to modify the reverse cholesterol transport model?
Authors: Alan R. Tall, Nan Wang, Phillip Mucksavage
Journal: Journal of Clinical Investigation (2001)

ABCA1 was recently identified as the mutant molecule in Tangier disease, a condition associated with very low HDL, cholesteryl ester accumulation in tissue macrophages, and an apparent increased risk of atherosclerotic cardiovascular disease.ABCA1 is an ATP-binding cassette transporter that facilitates the addition of phospholipids and cholesterol to free apoA-I, initiating the formation of HDL (1).ABCA1 is upregulated in cholesterolloaded cells, as a result of activation of LXR/RXR at the proximal promoter of the ABCA1 gene (2, 3).It has been proposed that increased expression of ABCA1 in macrophages or other tissues could activate the excretion of cholesterol via HDL and retard the development of atherosclerosis (3, 4).While we await the results of atherosclerosis studies, two reports in the JCI on ABCA1 knockout (KO) mice are notable, since they address different aspects of this hypothesis and reach some unexpected conclusions that call into question the accepted view of reverse cholesterol transport.
61. Successful Gene Therapy of a Mouse Model of Congenital Erythropoietic Porphyria with an Erythroid-Specific Lentiviral Vector
Authors: Elodie Robert, Magalie Lalanne, Isabelle Lamrissi-Garcia, Muriel Cario-Andre, Cecile Ged, Hubert De Verneuil, Francois Moreau-Gaudry
Journal: Molecular Therapy (2006)

Congenital erythropoietic porphyria (CEP) is a recessive autosomal disorder characterized by a deficiency in uroporphyrinogen III synthase (UROS), the fourth enzyme of the heme biosynthetic pathway. The severity of the disease, the lack of specific treatment except for allogenic bone marrow transplantation (BMT) and the knowledge of the molecular lesions are strong arguments towards gene therapy. We have recently developed a knock-in mouse model of CEP (Ged et al., Genomics, 2006) in order to evaluate the feasibility of gene therapy in haematopoietic stem cells (HSCs).
Gene Therapy for Alcoholism?
Authors: Brian Vastag
Journal: JAMA (2001)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
A comparison of aminolevulinic acid topical solution and blue light, aminolevulinic acid topical solution and a laser light source or topical 5-fluorouracil in broad area treatment of actinic keratoses of the face and scalp
Authors: Stacy R Smith, Daniel Piacquadio, Deborah Aiken, Richard Fitzpatrick
Journal: Journal of the American Academy of Dermatology (2004)
Postponement of Death Until Symbolically Meaningful Occasions
Authors: D P Phillips, D G Smith
Journal: JAMA (1990)

This study shows that mortality dips before a symbolically meaningful occasion and peaks just afterward. Mortality among Chinese (n = 1288) dips by 35.1% in the week before the Harvest Moon Festival and peaks by the same amount (34.6%) in the week after. We chose to study mortality among Chinese and a Chinese holiday for two reasons. First, the holiday moves around the calendar, thus allowing separation of the effects of the holiday from fixed, monthly mortality effects. Second, the holiday appeals strongly to one (experimental) group and not to others (which can be used as control groups). In terms of percentage, cerebrovascular diseases displayed the largest dip/peak pattern, followed by diseases of the heart, and then malignant neoplasms. The dip/peak mortality pattern does not appear in various non-Chinese control groups. The statistical significance of the findings was demonstrated with linear and curvilinear regression analysis and with two nonparametric tests. After testing alternative explanations for the findings, we concluded that the dip/peak pattern occurs because death can be briefly postponed until after the occurrence of a significant occasion. (<i>JAMA</i>. 1990;263:1947-1951)
Controlled release of PEI/DNA complexes from mannose-bearing chitosan microspheres as a potent delivery system to enhance immune response to HBV DNA vaccine
Authors: Xianfeng Zhou, Bin Liu, Xianghui Yu, Xiao Zha, Xizhen Zhang, Yu Chen, Xueyun Wang, Yinghua Jin, Yongge Wu, Yue Chen, Yaming Shan, Yan Chen, Junqiu Liu, Wei Kong, Jiacong Shen
Journal: Journal of Controlled Release (2007)
Relationship between tumor necrosis factor-alpha production and oxidative stress in the failing hearts of patients with dilated cardiomyopathy
Authors: Takayoshi Tsutamoto, Atsuyuki Wada, Tetsuya Matsumoto, Keiko Maeda, Naoko Mabuchi, Masaru Hayashi, Takashi Tsutsui, Masato Ohnishi, Masahide Sawaki, Masanori Fujii, Takehiro Matsumoto, Takashi Yamamoto, Hajime Horie, Yoshihisa Sugimoto, Masahiko Kinoshita
Journal: Journal of the American College of Cardiology (2001)
Hope Hype Hit-Reply
Authors: William M. Buchholz
Journal: JAMA (1990)

In Reply.—   first recorded medical reference is in the biblical Proverbs:  deferred maketh the heart sick. And: A merry heart doeth good like medicine. Hope's use as a panacea was documented by Cicero: While the sick man has life there is hope,1and again by Shakespeare: The miserable have no other medicine/But only hope.2   most current scientific literature on hope is found in studies of the placebo effect, where there is a consistent 30% to 40% response to placebo treatments regardless of the disease or nature of treatment.3The intentional use of placebo, however, raises questions on the ethics of false hope. As befitting a folk remedy, the most exhaustive study of the uses of hope is in the popular press.4   very nature of chronic disease requires multimodality therapy that is tailored to the individual patient. Hope should not be used
Tensile Strength of Irradiated Freeze-dried Arterial Grafts
Authors: T. Horne, A. V. Pollock, K. S. Zinnemann
Journal: BMJ (1959)

For several years in Leeds arterial homografts have been preserved by sterilization in /3-propiolactone followed by freeze-drying and storage in vacuo (Flewett et al., 1955; Zinnemann, 1957).Bacteriological and histological tests on these arteries after reconstitution have shown satisfactory sterilization and preservation of structure.Tensiometer tests have revealed a significant gain in tensile strength (unpublished observations).Recently we have been interested in the application of y-radiation from a cobalt or caesium source to the sterilization of arterial homografts.This paper deals with the effects of such irradiation on the tensile strength of freeze-dried human aortas.
Obama supports ban on therapy to change sexual orientation of youth
Authors: M. McCarthy
Journal: BMJ (2015)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Obama supports ban on therapy to change sexual orientation of youth Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Too many people
Authors: T. Smith
Journal: BMJ (1996)

When I look back on my time as a student in the 1950s one feature that stands out is the lack of crowds. Of course people were packed in together at football matches (where the stands were jammed with spectators who actually stood), but my memories of city centres in Britain and Europe are of plenty of room to get around; and when I recall walking in Yorkshire or camping in France the images are of vast open landscapes which looked empty. Roads had far fewer cars and lorries, especially back roads along which a cyclist could expect to meet only a handful of …
Specific elimination of cytotoxic effector cells. I. Adsorptive behavior of effectors and their precursors and spleen cell monolayers.
Authors: J R Neefe, D H Sachs
Journal: The Journal of Experimental Medicine (1976)

Monolayers formed of normal mouse spleen cells attached to polystyrene coated with poly-L-lysine were tested for their ability to bind specifically antigen-reactive cells in normal or primed mouse spleen. 88 to greater than 98% of the activity of cytotoxic populations was removed by a single adsorption. However, normal spleen cells or spleen cells previously primed in vitro could not be depleted of their capacity to be sensitized, even when adsorption effectively removed all residual cytotoxic activity from the same previously primed population. In fact, exposure to an immunoadsorbent augmented the ultimate cytotoxicity generated in a nonspecific fashion. This augmentation was especially dramatic in the case of a previously primed population and may have reflected the removal of a nonspecific suppressor. If antigen-reactive precursors cannot be removed efficiently by adsorption, other approaches to the generation of tolerant lymphoid populations, such as specific suppression of precursor differentiation must be sought.
THE DIPHASIC NATURE OF TUBERCULOSIS IN RABBITS AFTER INTRAVENOUS INOCULATION WITH BOVINE TUBERCLE BACILLI
Authors: R. M. Thomas
Journal: The Journal of Experimental Medicine (1932)

It has been shown that in a large group of rabbits inoculated intravenously with bovine tubercle bacilli the disease which follows resolves itself into two distinct phases. The first phase manifests itself in widespread diffuse lesions which subsequently regress. The mortality rate shows a rise and fall during this period, which have been correlated with the extent of lesions and with the changes in the blood cells. The duration of this phase is approximately 80 to 90 days. Following this period the mortality rate again rises and falls, during a period when all animals show lesions of a chronic nature. In an infected group the number of fatalities in the first phase is a function of the size of the dose. When the size of the dose and other conditions are held constant, a definite basis upon which to compare the reactions of treated animals is established. Studies of the blood cells during the course of the disease show that the changes in these cells reflect the course of the lesions in the first phase when other signs are lacking and offer a valuable means of making an estimate of the state of resistance of the animal from time to time. Studies of blood counts made on rabbits before their inoculation with tuberculosis were analyzed with regard to the relative longevity of the animals. It was found that those animals whose blood cells of various sorts deviated least from the modal value for the entire group survived longer than those animals whose counts were significantly high or low.
UK defies US by funding abortion programmes
Authors: Lynn Eaton
Journal: BMJ (2006)

The UK government is to contribute £3m ($5.3m; €4.4m) over the next two years to the global safe abortion programme.

The programme, developed by the International Planned Parenthood Federation, aims to help meet an internationally agreed target to reduce mortality among mothers in many of the world's poorest countries. It will help member associations do more to stop unsafe abortions as well as help halt the decline in family planning and reproductive services in some countries, such as Peru.

The UK government's contribution flies in the face of restrictions introduced by the US government on funding of such organisations. The US's “global gag rule” prevents federal funding of any organisation that is …
Tumor-Induced Osteomalacia -- Unveiling a New Hormone
Authors: Michael J. Econs, Marc K. Drezner
Journal: New England Journal of Medicine (1994)

Phosphate plays a critical part in the regulation of cell metabolism, and phosphate homeostasis is closely regulated in normal humans. Indeed, like serum calcium, serum phosphate is maintained within a narrow range of values, and people with abnormal concentrations may have a predisposition to life-threatening conditions, such as hemolysis, myopathy, hypocalcemia, and nephrocalcinosis.The principal organ that regulates phosphate homeostasis is the kidney. Regulation is accomplished partly through variation in glomerular filtration of phosphate but primarily through variation in renal tubular reabsorption of phosphate. These variations are detectable within 24 hours after a change in dietary phosphate intake and even . . .
A consistent approach for the application of pharmacokinetic modeling in cancer and noncancer risk assessment.
Authors: Harvey J Clewell, Melvin E Andersen, Hugh A Barton
Journal: Environmental Health Perspectives (2002)

Physiologically based pharmacokinetic modeling provides important capabilities for improving the reliability of the extrapolations across dose, species, and exposure route that are generally required in chemical risk assessment regardless of the toxic end point being considered. Recently, there has been an increasing focus on harmonization of the cancer and noncancer risk assessment approaches used by regulatory agencies. Although the specific details of applying pharmacokinetic modeling within these two paradigms may differ, it is possible to identify important elements common to both. These elements expand on a four-part framework for describing the development of toxicity: a) exposure, b) tissue dosimetry/pharmacokinetics, c) toxicity process/pharmacodynamics, and d) response. The middle two components constitute the mode of action. In particular, the approach described in this paper provides a common template for incorporating pharmacokinetic modeling to estimate tissue dosimetry into chemical risk assessment, whether for cancer or noncancer end points. Chemical risk assessments typically depend upon comparisons across species that often simplify to ratios reflecting the differences. In this paper we describe the uses of this ratio concept and discuss the advantages of a pharmacokinetic-based approach as compared to the use of default dosimetry.
Giardiasis with Malabsorption in X-Linked Agammaglobulinemia
Authors: Hans D. Ochs, Marvin E. Ament, Starkey D. Davis
Journal: New England Journal of Medicine (1972)

GASTROINTESTINAL disease is common among patients with variable immunodeficiency syndromes (IDS),1 2 3 4 but is rarely seen in patients with infantile X-linked agammaglobulinemia.2 , 5 In a recent study, Giardia lamblia was found to be the cause of gastrointestinal symptoms in seven of eight cases of variable IDS.6 G. lamblia caused a malabsorption syndrome in the patient with infantile X-linked agammaglobulinemia described below.Case ReportA 12-year-old boy with infantile X-linked agammaglobulinemia was admitted to the University Hospital, Seattle, in June, 1971, for a prospective study of the structure and function of the gastrointestinal tract in IDS. Results of studies of his immune system . . .
Enhanced Gene Expression in Mouse Lung after PEI–DNA Aerosol Delivery
Authors: Ajay Gautam, Charles L. Densmore, Bo Xu, J.Clifford Waldrep
Journal: Molecular Therapy (2000)

Aerosol gene delivery to the pulmonary system has vast potential for many diseases, including cystic fibrosis and lung cancer. We recently reported that polyethyleneimine (PEI), a cationic polymer, holds promise as a gene delivery vector for transfection in lung by aerosol. To further optimize the gene expression in the lung by aerosol, we utilized 5% CO2 in air for the nebulization of PEI–DNA complexes. Five percent CO2-in-air gave a threefold higher gene expression compared to normal air using the chloramphenicol acetyl transferase (CAT) reporter gene delivered by Aerotech II nebulizer. The delivery of DNA by PEI was dose dependent with the highest expression obtained when 2 mg of DNA in 10 ml was nebulized at a PEI nitrogen:DNA phosphate (N:P) ratio of 10:1. The optimal N:P ratio for lung transfection was found to be between 10:1 and 20:1 using the CAT and luciferase reporter genes. The time-course studies showed the highest expression at 24 h after aerosol delivery and 40–50% of peak level was detectable even after a week. Tissue distribution indicates the expression to be specific to the lung with no detectable expression in any other tissue examined. Histological and biochemical analysis of lungs revealed no evidence of acute inflammation. Aerosol gene delivery to the pulmonary system has vast potential for many diseases, including cystic fibrosis and lung cancer. We recently reported that polyethyleneimine (PEI), a cationic polymer, holds promise as a gene delivery vector for transfection in lung by aerosol. To further optimize the gene expression in the lung by aerosol, we utilized 5% CO2 in air for the nebulization of PEI–DNA complexes. Five percent CO2-in-air gave a threefold higher gene expression compared to normal air using the chloramphenicol acetyl transferase (CAT) reporter gene delivered by Aerotech II nebulizer. The delivery of DNA by PEI was dose dependent with the highest expression obtained when 2 mg of DNA in 10 ml was nebulized at a PEI nitrogen:DNA phosphate (N:P) ratio of 10:1. The optimal N:P ratio for lung transfection was found to be between 10:1 and 20:1 using the CAT and luciferase reporter genes. The time-course studies showed the highest expression at 24 h after aerosol delivery and 40–50% of peak level was detectable even after a week. Tissue distribution indicates the expression to be specific to the lung with no detectable expression in any other tissue examined. Histological and biochemical analysis of lungs revealed no evidence of acute inflammation.
Patients with congenital myasthenia associated with end-plate acetylcholinesterase deficiency show normal sequence, mRNA splicing, and assembly of catalytic subunits.
Authors: S Camp, S Bon, Y Li, D K Getman, A G Engel, J Massoulié, P Taylor
Journal: Journal of Clinical Investigation (1995)

A congenital myasthenic condition has been described in several patients characterized by a deficiency in end-plate acetylcholinesterase (AChE). The characteristic form of AChE in the end-plate basal lamina has the catalytic subunits disulfide linked to a collagen-like tail unit. Southern analysis of the gene encoding the catalytic subunits revealed no differences between patient and control DNA. Genomic DNA clones covering exon 4 and the alternatively spliced exons 5 and 6 were analyzed by nuclease protection and sequencing. Although allelic differences were detected between controls, we found no differences in exonic and intronic areas that might yield distinctive splicing patterns in patients and controls. The ACHE gene was cloned from genomic libraries from a patient and a control. Transfection of the cloned genes revealed identical species of mRNA and expressed AChE. Cotransfection of the genes expressing the catalytic subunits with a cDNA from Torpedo encoding the tail unit yielded asymmetric species that require assembly of catalytic subunits and tail unit. thus the catalytic subunits of AChE expressed in the congenital myasthenic syndrome appear identical in sequence, arise from similar splicing patterns, and assemble normally with a tail unit to form a heteromeric species.
The Primacy of Public Health Considerations in Defining Poor Quality Medicines
Authors: Paul N. Newton, Abdinasir A. Amin, Chris Bird, Phillip Passmore, Graham Dukes, Göran Tomson, Bright Simons, Roger Bate, Philippe J. Guerin, Nicholas J. White
Journal: PLoS Medicine (2011)

Paul Newton and colleagues argue that public health, and not intellectual property or trade issues, should be the prime consideration in defining and combating counterfeit medicines, and that the World Health Organization (WHO) should take a more prominent role.
Respiratory Tract Symptoms as a Clue to Giant Cell Arteritis
Authors: T. S. LARSON
Journal: Annals of Internal Medicine (1984)

Although many manifestations of giant cell arteritis are increasingly recognized, little attention has been paid to respiratory symptoms associated with this disorder. We report the cases of 16 patients with giant cell arteritis who had prominent symptoms related to the respiratory tract including cough, sore throat, and hoarseness. These symptoms were the initial finding in 10 patients and obscured the diagnosis in some instances, but resolved quickly when corticosteroids were given. It is estimated that 9% of patients with giant cell arteritis have prominent respiratory tract symptoms, which are the initial manifestion in 4%. This disorder should be considered in an older patient with a new cough or throat pain without obvious cause.