tbuckley/cabot-search huggingface dataset:
The Last GASP Wasn't
Authors: David M. Schachter
Journal: JAMA (1990)

<h3>To the Editor.—</h3> I found "The Last GASP"<sup>1</sup>offensive. There is great disagreement, even violent controversy, over the issue of animal experimentation. That we disagree should not be an excuse for disrespect in either direction. The article implies that it is ludicrous to be concerned about our treatment of beings other than ourselves and that the people who are so concerned are themselves fools or idiots. Is it really so ludicrous to be concerned about animals? Are we not mammals ourselves? Does anyone today truly suggest that animals do not experience fear and pain? We would not even think to do research on animals if not for the fact that they are similar enough to humans to make the research relevant. Physicians are meant to be compassionate beings. Disagreement is not an excuse for ugly arrogance toward any creatures or toward the opinions of other people. I don't think
Clofazimine, Psora-4 and PAP-1, inhibitors of the potassium channel Kv1.3, as a new and selective therapeutic strategy in chronic lymphocytic leukemia
Authors: L Leanza, L Trentin, K A Becker, F Frezzato, M Zoratti, G Semenzato, E Gulbins, I Szabo
Journal: Leukemia (2013)
Human hair shape is programmed from the bulb
Authors: S. Thibaut, O. Gaillard, P. Bouhanna, D.W. Cannell, B.A. Bernard
Journal: British Journal of Dermatology (2005)

Few biological data on curly hair follicles have been reported in the literature.To investigate the growth and morphology of curly hair follicles.Follicles were dissected from scalp skin samples from African, Guyanese and caucasian volunteers and were observed macroscopically, in culture in William's E medium, and by immunohistochemistry.Macroscopic study of scalp biopsies obtained from African volunteers showed that the dermal implantation of follicles was curved with a retrocurvature at the level of the bulb, as opposed to a straight shape in caucasian follicles. The bulb itself was bent, in the shape of a golf club, while both the outer root sheath (ORS) and the connective tissue sheath were dissymmetrical along the follicle. In vitro growth of curly hair follicles was slightly slower than that of caucasian follicles but, more importantly, the curvature was maintained in the hair shaft produced in vitro. As shown by immunohistochemistry, the proliferative matrix compartment of curly hair follicles was asymmetrical, Ki-67-labelled cells being more numerous on the convex side and extending above the Auber line. On the convex part of the follicle, the ORS was thinner and the differentiation programmes of the inner root sheath and hair shaft were delayed. Furthermore, some ORS cells expressed alpha-smooth muscle actin protein on the concave side of the curvature, reflecting a mechanical stress.Hair curliness is programmed from the bulb and is linked to asymmetry in differentiation programmes.
Stimulation of the nitric oxide synthase pathway in human hepatocytes by cytokines and endotoxin.
Authors: A K Nussler, M Di Silvio, T R Billiar, R A Hoffman, D A Geller, R Selby, J Madariaga, R L Simmons
Journal: The Journal of Experimental Medicine (1992)

Nitric oxide (NO) is a short-lived biologic mediator that is shown to be induced in various cell types and to cause many metabolic changes in target cells. Inhibition of tumor cell growth and antimicrobial activity has been attributed to the stimulation of the inducible type of the NO synthase (NOS). However, there is limited evidence for the existence of such inducible NOS in a human cell type. We show here the induction of NO biosynthesis in freshly isolated human hepatocytes (HC) after stimulation with interleukin 1, tumor necrosis factor (TNF), IFN-gamma, and endotoxin. Increased levels of nitrite (NO2-) and nitrate (NO3-) in culture supernatants were associated with NADPH-dependent NOS activity in the cell lysates. The production of NO2- and NO3- was inhibited by NG-monomethyl L-arginine and was associated with an increase in cyclic guanylate monophosphate release. The data presented here provide evidence for the existence of typical inducible NO biosynthesis in a human cell type.
Rapidly Progressive Pulmonary Infiltrates in Chronic Myelogenous Leukemia
Authors: David A. Taryle
Journal: JAMA (1979)

ALTHOUGH infection is the most common cause of pulmonary infiltrates in patients with leukemia,<sup>1</sup>other diagnostic considerations include drug-induced disease, hemorrhage, infarction, leukoagglutinin reaction, congestive heart failure, and the leukemic process itself.<sup>2</sup>It is unusual for leukemic infiltration to be a major clinical problem, although pathologically it occurs relatively frequently.<sup>3</sup> <h3>Report of a Case</h3> A 35-year-old woman was admitted to the hospital on Nov 5, 1976, with fever and cough. Philadelphia chromosome-positive chronic myelogenous leukemia had been diagnosed in 1974 following a year of purpura. The patient had received intermittently busulfan, 4 to 8 mg/day for one year, at which time thioguanine was added. In January 1976 Bacillus Calmette-Guérin immunotherapy was instituted. Five months later, pleuropericarditis of unknown origin developed, and isoniazid therapy was given. In July 1976 early myeloblast transformation occurred. Demecolcine, thioguanine, prednisone, and vinblastine sulfate were given, and a splenectomy was performed. No further busulfan
Modulation of Iron Uptake in Heart by L-Type Ca <sup>2+</sup> Channel Modifiers
Authors: Robert G. Tsushima, Alan D. Wickenden, Ron A. Bouchard, Gavin Y. Oudit, Peter P. Liu, Peter H. Backx
Journal: Circulation Research (1999)

Abstract —Heart failure is the leading cause of mortality in patients with transfusional iron (Fe) overload in which myocardial iron uptake ensues via a transferrin-independent process. We examined the ability of L-type Ca 2+ channel modifiers to alter Fe 2+ uptake by isolated rat hearts and ventricular myocytes. Perfusion of rat hearts with 100 nmol/L 59 Fe 2+ and 5 mmol/L ascorbate resulted in specific 59 Fe 2+ uptake of 20.4±1.9 ng of Fe per gram dry wt. Abolishing myocardial electrical excitability with 20 mmol/L KCl reduced specific 59 Fe 2+ uptake by 60±7% ( P &lt;0.01), which suggested that a component of myocardial Fe 2+ uptake depends on membrane voltage. Accordingly, 59 Fe 2+ uptake was inhibited by 10 μmol/L nifedipine (45±12%, P &lt;0.02) and 100 μmol/L Cd 2+ (86±3%; P &lt;0.001) while being augmented by 100 nmol/L Bay K 8644 (61±18%, P &lt;0.01) or 100 nmol/L isoproterenol (40±12%, P &lt;0.05). By contrast, uptake of 100 nmol/L ferric iron ( 59 Fe 3+ ) was significantly lower (1.4±0.3 ng Fe per gram dry wt; P &lt;0.001) compared with divalent iron. These data suggest that a component of Fe 2+ uptake into heart occurs via the L-type Ca 2+ channel in myocytes. To investigate this further, the effects of Fe 2+ on cardiac myocyte L-type Ca 2+ currents were measured. In the absence of Ca 2+ , noninactivating nitrendipine-sensitive Fe 2+ currents were recorded with 15 mmol/L [Fe 2+ ] o . Low concentrations of Fe 2+ enhanced Ca 2+ current amplitude and slowed inactivation rates, which was consistent with Fe 2+ entry into the cell, whereas higher Fe 2+ levels caused dose-dependent decreases in peak current. Fe 3+ had no effect on current amplitude or decay. Combined, our data suggest that myocardial Fe 2+ uptake occurs via L-type Ca 2+ channels and that blockade of these channels might be useful in the treatment of patients with excessive serum iron levels.
EFPIA-PhRMA's principles for clinical trial data sharing have been misunderstood
Authors: P. Doshi
Journal: BMJ (2013)

The recent joint statement of the European Federation of Pharmaceutical Industries and Associations (EFPIA) and the Pharmaceutical Research and Manufacturers of America (PhRMA) of their principles for responsible sharing of clinical trial data1 has been misunderstood in two important ways, exaggerating the perceived progressiveness of the principles.

Firstly, despite reports that all member drug companies have agreed to set up independent or external review panels to judge third party requests for …
Host Resistance in Relation to Survival in Breast Cancer
Authors: M. Di Paola, L. Angelini, A. Bertolotti, S. Colizza
Journal: BMJ (1974)

The degree of lymphocytic infiltration in and around breast tumours together with sinus histiocytosis and follicular hyperplasia in regional lymph nodes has been studied in 310 cases of breast cancer treated with standard radical mastectomy. The presence of these features was regarded as evidence of host resistance against the tumour and made possible the division of patients into three classes—no or poor reaction, good reaction, and strong reaction. The grading was shown to have a close correlation with prognosis. The relationship between host defensive factor grading and malignancy, nodal metastases, and survival was also examined. The results support the hypothesis that prognosis in breast cancer is closely related to a histological picture of cell-mediated immunity against the tumour.
Endoscopy for Broncholith
Authors: Charles O. Brantigan
Journal: JAMA (1978)

To the Editor.—  I read with interest the article by Lin and Becker entitled Broncholith as a Cause of Fatal Hemoptysis (239:2153, 1978). Drs Lin and Becker failed to make one important point in the endoscopic treatment of patients with endobronchial hemorrhage secondary to a broncholith. The endoscopists must resist the temptation to grasp the offending broncholith with a forcep in an attempt at extraction. If the broncholith is removed under these circumstances, massive and uncontrollable hemorrhage often follows. It would be far superior, after identifying the bronchus from which the bleeding is occurring, to occlude this bronchus either by using gauze packing introduced through the bronchoscope or by occluding the bronchus using a standard Fogarty catheter. Such treatment will keep the patient from drowning in his own blood while awaiting definitive surgical therapy. A rigid bronchoscope is obviously required for such manipulations.
Trouble with health maintenance organisations.
Authors: C. R. Paton
Journal: BMJ (1988)

injuring the chosen segment.'7Sadly, the procedure is often left to the unsupervised beginner.All biopsy specimens should be serially sectioned because skip lesions as short as 0 35 mm may occur.'8Biopsy ofthe temporal artery remains a useful confirmatory investigation in patients with giant cell arteritis.Long term treatment with corticosteroids and follow up may be started confidently if histological proof of the condition is obtained.The decision to treat the minority of patients in whom the findings on biopsy are negative must be made on clinical grounds.If the diagnosis is seriously suspected prompt treatment should be started without waiting for confirmation from biopsy.
Functional Evaluation and Rehabilitation of Cardiac Patients
Authors: David L. Abrams
Journal: JAMA (1979)

This book, the proceedings of an international symposium held in Stresa, Italy, in May 1977, is not as all encompassing as the title suggests. The foreword states that only the functional evaluation and rehabilitation of patients with myocardial infarction are considered. Topics presented include an evaluation of stress testing, correlation of coronary artery angiography and stress testing, objective evaluation of the results of aortocoronary bypass and heart transplantations, and early and late rehabilitation of the patient with a myocardial infarction. Although there are several excellent articles, others are superficial, and the book at best serves only as a brief, dated, and limited overview of an important area of cardiology today. Its publication more than two years following the actual symposium tends to reduce it to a historical record rather than a survey of current knowledge and opinion. The translation into English is flawed and less than fluent, at times leading
The Menace of Irrational Legal Processes
Authors: Howard A. Kelly
Journal: JAMA (1913)

To the Editor:  —We have all recently passed through a distressing experience here in Baltimore on account of an outrageously unjust decision of our court in a malpractice suit against Dr. Guy L. Hunner. My own utter disgust with the methods of the legal profession is such that if I were to act on the impulse of the moment I would abandon my surgical work, and retire to some distant field to escape as far as possible from the nauseating associations with courts and their wearing delays and postponements and their processes of flagrant injustice.  The case was this: Dr. Hunner operated on a woman with a large perinephritic tuberculous abscess. The lower pole of the kidney was calcareous and tuberculous; he did a remarkable conservative operation, resecting the diseased portion and saving a good organ which has healed perfectly and given no further trouble. The surrounding tuberculous abscess cavity
Laetrile for the Terminally Ill: Supreme Court Stops the Nonsense
Authors: William J. Curran
Journal: New England Journal of Medicine (1980)

Over the past five years there has been a growing wave of loudly expressed and widely distributed protest against what has been called "improper interference" by hospitals, physicians, and government regulatory agencies in the "free choice" of patients with cancer to obtain Laetrile, a compound of seeds and kernels of various fruits, as a cure for the disease. The stridency of much of the public media in supporting this movement has been especially painful to us in Massachusetts, the home state of the tragic case of Chad Green. Chad Green died of leukemia in Mexico after being taken there by . . .
MATURATION OF B LYMPHOCYTES IN THE RAT
Authors: Samuel Strober, Jeanette Dilley
Journal: The Journal of Experimental Medicine (1973)

The migration pattern, tissue distribution, and turnover rate of unprimed and primed B lymphocytes involved in the adoptive anti-DNP response was studied. The adoptive primary response restored by unprimed spleen or thoracic duct cells passaged through an intermediate host (intravenous injection and subsequent collection in the thoracic duct lymph) was markedly diminished as compared with that restored by unpassaged cells. On the other hand, the adoptive response restored by passaged spleen or thoracic duct cells from DNP-primed donors was greater than or the same as that restored with unpassaged cells, respectively. This suggests that unprimed B cells change from nonrecirculating to recirculating lymphocytes after exposure to antigen. Studies of the adoptive anti-DNP response restored by unprimed or primed bone marrow cells showed little change in the time-course or amplitude of the response restored by either population of cells. The relative inability of marrow cells to carry immunological memory was related to the inability of recirculating memory cells to penetrate the marrow. The turnover rate of unprimed and primed B cells was investigated by treating the cell donors with [(3)H]thymidine for 48 h before removal of thoracic duct or spleen cells. The adoptive anti-DNP response restored by unprimed or primed cells was not affected by [(3)H]thymidine treatment. This indicates that both populations of cells turn over slowly. However, our previous studies show that unprimed B cells involved in the adoptive antibody response to ferritin turn over rapidly. The different findings are discussed in the context of antigen-dependent B-cell maturation.
Optimization of hCFTR Lung Expression in Mice Using DNA Nanoparticles
Authors: Linas Padegimas, Tomasz H Kowalczyk, Sam Adams, Chris R Gedeon, Sharon M Oette, Karla Dines, Susannah L Hyatt, Ozge Sesenoglu-Laird, Olena Tyr, Robert C Moen, Mark J Cooper
Journal: Molecular Therapy (2011)

Efficient and prolonged human cystic fibrosis transmembrane conductance regulator (hCFTR) expression is a major goal for cystic fibrosis (CF) lung therapy. A hCFTR expression plasmid was optimized as a payload for compacted DNA nanoparticles formulated with polyethylene glycol (PEG)-substituted 30-mer lysine peptides. A codon-optimized and CpG-reduced hCFTR synthetic gene (CO-CFTR) was placed in a polyubiquitin C expression plasmid. Compared to hCFTR complementary DNA (cDNA), CO-CFTR produced a ninefold increased level of hCFTR protein in transfected HEK293 cells and, when compacted as DNA nanoparticles, produced a similar improvement in lung mRNA expression in Balb/c and fatty acid binding protein promoter (FABP) CF mice, although expression duration was transient. Various vector modifications were tested to extend duration of CO-CFTR expression. A novel prolonged expression (PE) element derived from the bovine growth hormone (BGH) gene 3' flanking sequence produced prolonged expression of CO-CFTR mRNA at biologically relevant levels. A time course study in the mouse lung revealed that CO-CFTR mRNA did not change significantly, with CO-CFTR/mCFTR geometric mean ratios of 94% on day 2, 71% on day 14, 53% on day 30, and 14% on day 59. Prolonged CO-CFTR expression is dependent on the orientation of the PE element and its transcription, is not specific to the UbC promoter, and is less dependent on other vector backbone elements.
Healthy alliances with drug dealers
Authors: J Neeleman, R Beaseley, M Farrell
Journal: BMJ (1994)

EDITOR, - We wish to report a novel approach to “healthy alliances”1 in the supply end of the drug market.

A 33 year old man of no fixed abode had a long history of opiate and benzopdiazepine dependence. Before his referral he had been in constant contact with his local drugs dealer and had managed, with her help, to switch from injectable heroin to oral methadone. As …
Polyethylene glycol-conjugated hyaluronic acid-ceramide self-assembled nanoparticles for targeted delivery of doxorubicin
Authors: Hyun-Jong Cho, In-Soo Yoon, Hong Yeol Yoon, Heebeom Koo, Yu-Jin Jin, Seung-Hak Ko, Jae-Seong Shim, Kwangmeyung Kim, Ick Chan Kwon, Dae-Duk Kim
Journal: Biomaterials (2011)
Contrast Media–Enhanced Magnetic Resonance Imaging Visualizes Myocardial Changes in the Course of Viral Myocarditis
Authors: Matthias G. Friedrich, Oliver Strohm, Jeanette Schulz-Menger, Heinz Marciniak, Friedrich C. Luft, Rainer Dietz
Journal: Circulation (1998)

The course of tissue changes in acute myocarditis in humans is not well understood. Diagnostic tools currently available are unsatisfactory. We tested the hypothesis that inflammation is reflected by signal changes in contrast-enhanced magnetic resonance imaging (MRI).We assessed 44 consecutive patients with symptoms of acute myocarditis. Nineteen patients met the inclusion criteria revealing ECG changes, reduced myocardial function, elevated creatine kinase, positive troponin T, serological evidence for acute viral infection, exclusion of coronary heart disease, and positive antimyosin scintigraphy. We studied these patients on days 2, 7, 14, 28, and 84 after the onset of symptoms. We obtained ECG-triggered, T1-weighted images before and after application of 0.1 mmol/kg gadolinium. We measured the global relative signal enhancement of the left ventricular myocardium related to skeletal muscle and compared it with measurements in 18 volunteers. The global relative enhancement was higher in patients on days 2 (4.8+/-0.3 [mean+/-SE] versus 2.5+/-0.2; P<.0001); 7 (4.7+/-0.5, P<.0001); 14 (4.6+/-0.5, P<.0002); and 28 (3.9+/-0.4, P=.009) but not on day 84 (3.1+/-0.3; P=NS). On day 2, the enhancement was focal, whereas at later time points, the enhancement was diffuse. In patients with evidence of ongoing disease, the values remained elevated.Acute myocarditis evolves from a focal to a disseminated process during the first 2 weeks after onset of symptoms. Contrast media-enhanced MRI visualizes the localization, activity, and extent of inflammation and may serve as a powerful noninvasive diagnostic tool in acute myocarditis.
Structure and distribution of an Alu-type deletion mutation in Sandhoff disease.
Authors: K Neote, B McInnes, D J Mahuran, R A Gravel
Journal: Journal of Clinical Investigation (1990)

Sandhoff disease is a recessively inherited lysosomal storage disease resulting from a deficiency of beta-hexosaminidase activity. The enzyme occurs in two major forms, beta-hexosaminidase A, composed of an alpha- and beta-subunit and beta-hexosaminidase B, composed of two beta-subunits. Both isozyme activities are deficient in Sandhoff disease, owing to mutations of the HEXB gene encoding the common beta-subunit. We have cloned and fully characterized a deletion at the HEXB gene from fibroblasts of a patient with the infantile form of Sandhoff disease. The deletion removes approximately 16 kb of DNA including the HEXB promoter, exons 1-5 and part of intron 5. It most likely arose from recombination between two Alu sequences, with the breakpoints occurring at the midpoint between the left and right arms in each case and regenerating an intact Alu element in the deletion sequence. The deletion allele accounts for 27% of the Sandhoff mutant alleles we analyzed. Two cell lines were shown to be homozygous for the deletion and both had the infantile form of the disease. Four additional patients were compound heterozygotes with other mutations, all of whom displayed a different clinical phenotype. Finally, the mutant allele was present in different ethnic backgrounds, suggesting that it may have been subject to genetic drift.
A Lecture ON THE RED DEGENERATION OF UTERINE FIBROIDS COMPLICATING PREGNANCY: Delivered at the Medical Graduates' College and Polyclinic, May 5th, 1909
Authors: J. Bland-Sutton
Journal: BMJ (1909)

OF all the genera of tumours to which women are liabl, the uterine fibroid is the most common, and there is no genus ,f tumours which has such a definite age-distribu- tion.Though the uterine fibroid is such a common tumour, like pregnancy, it only arises during the menstrual period of life, which in Great Britain covers an average period of thirty years, from the fifteenth to the forty-fifth.There is, however, this difference-from the twentieth to the thirtieth year pregnancy is extremely common, the occur- rence of a large fibroid uncommon.From the thirtieth
Alan Benjamin Otlet
Authors: A. B Lavelle
Journal: BMJ (2009)

After professorial house jobs, Alan Benjamin Otlet became a principal in general practice in Southmead, Bristol. He had a particular interest in obstetrics, becoming GP adviser to Southmead Hospital. In particular, he took on intrapartum care for a number of local practices, keeping meticulous notes in every case. In total, he was …
Differential Recognition of Target Genes by Nuclear Receptor Monomers, Dimers, and Heterodimers*
Authors: CHRISTOPHER K. GLASS
Journal: Endocrine Reviews (1994)

NUCLEAR receptors regulate the transcription of complex networks of genes and thereby control diverse aspects of growth, development, and homeostasis. The nuclear receptor superfamily includes intracellular receptors for steroid hormones, thyroid hormones, and retinoids, as well as a large number of related proteins for which regulatory ligands have not been identified. Regardless of whether transcriptional activity is controlled by the binding of a ligand, each of these proteins must be capable of binding to specific DNA sequences that identify particular genes as targets for regulation. Elucidation of the mechanisms that underlie gene-specific recognition therefore forms a central problem in understanding how various members of the nuclear receptor superfamily function to differentially regulate gene expression. The sequence-specific DNA binding properties of nuclear receptors are determined by two conserved domains that function in an interdependent manner to mediate protein-DNA and protein-protein interactions (Fig. 1). Protein-DNA interactions are mediated by the highly conserved DNA binding domain (DBD) that defines the nuclear receptor superfamily.