tbuckley/cabot-search huggingface dataset:
Hay fever drug to become prescription only
Authors: J. Wise
Journal: BMJ (1997)

We showed previously that the attachment of synovial fibroblasts to laminin (LM)-111 in the presence of transforming growth factor-β induces significant expression of the matrix metalloproteinase (MMP)-3. Here we go on to investigate the regulation of additional MMPs and their specific tissue inhibitors of matrix proteases (TIMPs). Changes in steady-state mRNA levels encoding TIMPs and MMPs were investigated by quantitative reverse transcription–polymerase chain reaction. Production of MMPs was monitored by a multiplexed immunoarray. Signal transduction pathways were studied by immunoblotting. Attachment of synovial fibroblasts to LM-111 in the presence of transforming growth factor-β induced significant increases in MMP-3 mRNA (12.35-fold, p&lt;0.001) and protein (mean 62 ng/ml, sixfold, p&lt;0.008) and in expression of MMP-10 mRNA (11.68-fold, p&lt;0.05) and protein (54 ng/ml, 20-fold, p⩾0.02). All other TIMPs and MMPs investigated failed to show this LM-111-facilitated transforming growth factor-β response. No phosphorylation of nuclear factor-κB was observed. We conclude that co-stimulation of synovial fibroblasts by LM-111 together with transforming growth factor-β suffices to induce significant expression of MMP-3 and MMP-10 by synovial fibroblasts and that this induction is independent of nuclear factor-κB phosphorylation.
Serum Brain-Derived Neurotrophic Factor as a Predictor of Incident Dementia—Reply
Authors: Galit Weinstein, Sudha Seshadri
Journal: JAMA Neurology (2014)

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 Neurology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Neurology journal
Pituitary-adrenal Function in Cases of Pituitary Tumour
Authors: V. Marks, M. Summers
Journal: BMJ (1963)

A case of post-operative hypotension due to paroxysmal atrial tachycardia with block is described.It was due to digitalis intoxication in the presence of potassium deficiency, and the possible aetiological factors include the normal metabolic response to trauma.We wish to thank Dr. J. A.
D-Penicillamine Induced Goodpasture's Syndrome in Wilson's Disease
Authors: IRMIN STERNLIEB
Journal: Annals of Internal Medicine (1975)

Fatal pulmonary hemorrhages and rapidly progressive glomerulonephritis occurred in three patients with Wilson's disease (hepatolenticular degeneration) who had been treated with penicillamine for 2 to 3½ years. Light microscopic studies of the kidneys showed severe glomerulonephritis with crescent formation, and the lungs showed intraalveolar hemorrhages. Although the clinical and pathologic abnormalities were those of Goodpasture's syndrome, immunofluorescence microscopic studies in the one case tested showed an interrupted, rather than linear, fluorescence pattern.
WITH THE CLINICAL ACCOUNT OF A CASE
Authors: WALTER FREUDENTHAL, R. G. ANDERSON, F.PARKES WEBER
Journal: British Journal of Dermatology (1937)

Journal Article WITH THE CLINICAL ACCOUNT OF A CASE Get access WALTER FREUDENTHAL, M.D., WALTER FREUDENTHAL, M.D. Search for other works by this author on: Oxford Academic Google Scholar R. G. ANDERSON, M.D., R. G. ANDERSON, M.D. Search for other works by this author on: Oxford Academic Google Scholar F.PARKES WEBER, M.D. F.PARKES WEBER, M.D. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 49, Issue 4, 1 April 1937, Pages 151–162, https://doi.org/10.1111/j.1365-2133.1937.tb11173.x Published: 01 April 1937
Specific receptors for leukotriene C4 on a smooth muscle cell line.
Authors: S Krilis, R A Lewis, E J Corey, K F Austen
Journal: Journal of Clinical Investigation (1983)

Specific receptors for leukotriene C4 (LTC4) have been identified on an intact smooth muscle cell line, DDT1 MF-2 cells derived from the Syrian hamster vas deferens. Specific [3H]LTC4 binding at a fixed input at 4 degrees C was rapid, reached a plateau at 86% of total binding at 60 min, and was reversible upon addition of excess homoligand. With incremental inputs of radioligand and a constant cell number, specific [3H]LTC4 binding reached a plateau indicative of saturable binding sites. LIGAND analysis of the Scatchard plot demonstrated a single high affinity binding site with a dissociation constant (Kd) of 5 nM. With incremental inputs of unlabeled LTC4, LIGAND analysis of the Scatchard plot demonstrated a single high affinity site with a Kd of 4.4 nM and in some experiments an additional low affinity site with a Kd of 634 nM. The myotonically active structural analogues of LTC4, 5(R),6(S)-LTC4, 11-trans-LTC4, and C1-monoamide-LTC4, competed effectively with radiolabeled LTC4 such that the relative Kd values of these heteroligands were within one log of that of the homoligand. In contrast, the other native sulfidopeptide leukotrienes, leukotriene D4 and leukotriene E4, exhibited relative Kd values that were 2-3 logs less than that of LTC4. Thus, the high affinity receptor on the DDT1 smooth muscle cell line is specific for a single constituent, LTC4, of slow reacting substance of anaphylaxis.
Effect of thoracentesis on pulmonary gas exchange.
Authors: M Perpina, E Benlloch, V Marco, F Abad, D Nauffal
Journal: Thorax (1983)

The effect of thoracentesis on pulmonary gas exchange was studied in 33 patients with unilateral pleural effusions of various causes. Arterial blood gases were measured before thoracentesis and at 20 minutes, two hours, and 24 hours after the procedure. In 13 patients alveolar arterial oxygen gradient (PA-ao2), physiological dead space:tidal volume ratio (VD/VT), physiological shunt, and "anatomical" shunt were also determined before and two hours after thoracentesis. The Pao2 showed a significant increase at each time, reaching a maximum at 24 hours (mean (SD) increase 1.1 (0.74) kPa; 8.17 (5.57) mm Hg). A concurrent significant decrease of PA-ao2 was observed (mean (SD) 1.72 (0.77) kPa; 12.92 (5.78) mm Hg). This was accompanied by a small but significant decrease of "anatomical" shunt (2.4% (1.5%] and a greater decrease of the physiological shunt (6.5% (4.3%], while VD/VT did not change. The results are probably due to improved ventilation perfusion relationships with, in particular, an increase in the ventilation of parts of the lung previously poorly ventilated but well perfused.
Should Health Care Systems Become Insurers?
Authors: Nirav R. Shah, Dave A. Chokshi
Journal: JAMA (2013)

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
S52 Association of microtubule instability with defective phagocytosis in COPD
Authors: C. M. R. Thomas, A. E. Taylor, P. Bruijnzeel, J. A. Wedzicha, P. J. Barnes, L. E. Donnelly
Journal: Thorax (2011)

<h3></h3> Acute exacerbations of COPD are the commonest cause of acute medical admissions in the UK and ∼50% are associated with bacterial infection. Alveolar macrophages (AM) normally clear inhaled bacteria but defective phagocytosis may lead to chronic colonisation and increased exacerbations. Monocyte-derived macrophages (MDM), used to model AM, were obtained from COPD, smoking and healthy subjects. MDM phagocytosis of fluorescently-labelled polystyrene beads, <i>Haemophilus influenzae</i> (HI) or <i>Streptococcus pneumoniae</i> (SP) was measured by fluorimetry. MDM derived from all subjects showed equivalent ability to phagocytose beads, however, COPD and smoker MDM showed significantly reduced phagocytosis of bacteria. Phagocytosis of HI was reduced by 28% and 48% in COPD and smoker MDM respectively, compared to healthy, while SP phagocytosis was reduced by 32% and 52% in COPD and smoker MDM respectively, compared to healthy (Abstract S52 table 1). Having identified defective bacterial phagocytosis in smoker and COPD MDM, the next step was to elucidate the underlying mechanism. Cytoskeletal rearrangement was investigated, with COPD MDM showing significantly reduced phagocytosis of bacteria in comparison to healthy after pre-incubation with nocodazole (microtubule disruptor). Microtubules are involved in membrane trafficking of the phagolysosome and microtubule stability is necessary for effective phagocytosis. Tubulin is acetylated to form stable microtubules and is deacetylated by HDAC6 and Sirt2. COPD MDM showed reduced levels of acetylated tubulin compared to healthy MDM. Pre-incubation with epothilone B (10 nm) a microtubule stabiliser, improved HI phagocytosis in COPD MDM by 20% (p&lt;0.05) and SP phagocytosis in smoker MDM by 40%. Levels of acetylated tubulin increased on exposure to bacteria alone in healthy and smoker MDM but not in COPD MDM. Pre-incubation with epothilone B was associated with significantly increased levels of acetylated tubulin in COPD cells. No significant differences were seen in the expression of HDAC6 or Sirt2 in COPD compared to healthy cells. MDM from smoking and COPD subjects show reduced phagocytosis of common respiratory bacterial pathogens. Acetylation of microtubules appears to be reduced in COPD, whereas, increasing tubulin acetylation is associated with improvements in phagocytosis, which may allow for targeted development of future therapies to treat colonisation and prevent exacerbations of COPD.
Humoral Immune Response against Nontargeted Tumor Antigens after Treatment with Sipuleucel-T and Its Association with Improved Clinical Outcome
Authors: Debraj GuhaThakurta, Nadeem A. Sheikh, Li-Qun Fan, Harini Kandadi, T. Craig Meagher, Simon J. Hall, Philip W. Kantoff, Celestia S. Higano, Eric J. Small, Thomas A. Gardner, Kate Bailey, Tuyen Vu, Todd DeVries, James B. Whitmore, Mark W. Frohlich, James B. Trager, Charles G. Drake
Journal: Clinical Cancer Research (2015)

Abstract Purpose: Antitumor activity of cancer immunotherapies may elicit immune responses to nontargeted (secondary) tumor antigens, or antigen spread. We evaluated humoral antigen spread after treatment with sipuleucel-T, an immunotherapy for asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC), designed to target prostatic acid phosphatase (PAP; primary antigen). Experimental Design: Serum samples from patients with mCRPC enrolled in the placebo-controlled phase III IMPACT study (evaluable n = 142) were used to assess humoral antigen spread after treatment with sipuleucel-T. Immunoglobulin G (IgG) responses to self-antigens (including tumor antigens) were surveyed using protein microarrays and confirmed using Luminex xMAP. IgG responses were subsequently validated in ProACT (n = 33), an independent phase II study of sipuleucel-T. Association of IgG responses with overall survival (OS) was assessed using multivariate Cox models adjusted for baseline prostate-specific antigen (PSA) and lactate dehydrogenase levels. Results: In patients from IMPACT and ProACT, levels of IgG against multiple secondary antigens, including PSA, KLK2/hK2, K-Ras, E-Ras, LGALS8/PCTA-1/galectin-8, and LGALS3/galectin-3, were elevated after treatment with sipuleucel-T (P &amp;lt; 0.01), but not control. IgG responses (≥2-fold elevation posttreatment) occurred in ≥25% of patients, appeared by 2 weeks after sipuleucel-T treatment, and persisted for up to 6 months. IgG responses to PSA and LGALS3 were associated with improved OS in sipuleucel-T–treated patients from IMPACT (P ≤ 0.05). Conclusions: Sipuleucel-T induced humoral antigen spread in patients with mCRPC. IgG responses were associated with improved OS in IMPACT. The methods and results reported may identify pharmacodynamic biomarkers of clinical outcome after sipuleucel-T treatment, and help in clinical assessments of other cancer immunotherapies. Clin Cancer Res; 21(16); 3619–30. ©2015 AACR. See related commentary by Hellstrom and Hellstrom, p. 3581
Clinical applications of growth hormone for ovarian stimulation
Authors: R Homburg
Journal: Human Reproduction Update (1995)

Journal Article Clinical applications of growth hormone for ovarian stimulation Get access Roy Homburg, Roy Homburg 1Infertility Unit, Golda Medical CenterPetah Tikva 49372, Israel Search for other works by this author on: Oxford Academic PubMed Google Scholar Hanne Ostergaard Hanne Ostergaard 2Novo Nordisk A/SGentofte, Denmark Search for other works by this author on: Oxford Academic PubMed Google Scholar Human Reproduction Update, Volume 1, Issue 3, 1 January 1995, Pages 264–275, https://doi.org/10.1093/humupd/1.3.264 Published: 01 May 1995 Article history Received: 14 January 1994 Accepted: 11 October 1994 Published: 01 May 1995
Utilisation of joint movement range in arboreal primates compared with human subjects: an evolutionary frame for primary osteoarthritis.
Authors: C J Alexander
Journal: Annals of the Rheumatic Diseases (1994)

OBJECTIVE--To determine whether an arboreal lifestyle required full use of movement ranges underutilised in nine joint groups in humans, because under-utilisation of available movement range may be associated with susceptibility to primary osteoarthritis. METHODS--Utilisation of the nine joint groups was studied in two species of primate exercising in a simulated arboreal environment, using 9focal animal9 observation techniques supplemented by telephoto photography and by review of archival material from other sources. Fifteen apes were observed over a total observation period of 20.2 man-hours and 152 films were analysed for utilisation of movement range. RESULTS--With one exception, all the movement ranges reported to be under-utilised in humans were fully utilised by the apes in climbing activities. The exception, metacarpophalangeal extension, was an essential component of the chimpanzee ground progression mode of knuckle walking. CONCLUSIONS--The underused movement range in several human joints is explicable as residual capacity from a semiarboreal lifestyle. If the correlation with primary osteoarthritis is confirmed, it suggests that the disease may reflect a disparity between inherited capacity and current need. The significance of the result lies in its implication that primary osteoarthritis may be preventable.
Power Unseen: How Microbes Rule the World
Authors: Henry Wilde
Journal: JAMA (1995)

Reading Paul De Kruifs Microbe Hunters must have stimulated many a young student of my generation toward a career in medicine or microbiology. Now reading Dixon's book is like a deja vu experience with a modernized version of the same topic. The author provides even a physician-reader with new insights into microbiology and its profound effect on our health and economic and ecological existence.  Chapters dealing with advances in molecular biology of microbes, vaccines, and industrial applications of bacteriology and mycology are all well researched and written in an interesting and even entertaining manner. As such, the book makes good reading for any audience with an interest in the biological sciences and any who wish to broaden their horizons.  No book like this, however, is without some flaws. The one that struck me immediately is Dixon's rather incomplete and perhaps unfair assessment of Louis Pasteur's work. Was Pasteur indeed an
Dynamic Radiology of the Abdomen: Normal and Pathologic Anatomy
Authors: John R. Amberg
Journal: JAMA (1983)

The second edition of Dr Meyers' book is welcome. The first edition became enormously popular, since it had great applications to ultrasonography and computed tomography of the abdomen as well as then-conventional radiologic techniques. Ultrasound and computed tomography have matured considerably in the last six years and have become extremely important in abdominal imaging. This development required Dr Meyers to revise and expand the book. The new volume contains many more cross-sectional images, and they complement the text very well. The effectiveness of this book lies in the approach to the abdomen. Instead of the usual organ system approach, Dr Meyers' concept is that the abdomen is a place. In this place, there is a lot of interaction. He deems it inadequate to think of the pancreas as a quiet little retroperitoneal organ that keeps to itself. He describes and explains why the manifestations of pancreatic disease can be found
The Battering Child
Authors: Lester Adelson
Journal: JAMA (1972)

Five infants, all less than 1 year of age, were killed by children 8 years old or younger. All five died from craniocerebral trauma resulting from assaults with a blunt instrument, being dropped to the floor, or both. Two had been bitten by their juvenile attackers. None of the victims showed any stigmata of adult "battering" in the form of multiple, nonlethal metasynchronous trauma, and adult involvement in the fatal terminal episode was excluded by thorough police investigation. The delicacy of the soft and bony structures of the infant's head renders it vulnerable to mortal trauma at the hands of tiny assailants. The preschool child is capable of homicidal rage when he is provoked by what he considers to be a threat to his sense of social security in his family unit or immediate human environment.
Serotonergic systems targeted by developmental exposure to chlorpyrifos: effects during different critical periods.
Authors: Justin E Aldridge, Frederic J Seidler, Armando Meyer, Indira Thillai, Theodore A Slotkin
Journal: Environmental Health Perspectives (2003)

During brain development, serotonin (5HT) provides essential neurotrophic signals. In the present study, we evaluated whether the developmental neurotoxicity of chlorpyrifos (CPF) involves effects on 5HT signaling, as a potential mechanism underlying noncholinergic neuroteratogenic events. We evaluated four different treatment windows ranging from the neural tube stage [gestational days (GD) 9-12] and the late gestational period (GD17-20) through postnatal phases of terminal neuronal differentiation and synaptogenesis [postnatal days (PN) 1-4, PN11-14]. Exposure to CPF on GD9-12 elicited initial suppression, immediately followed by rebound elevation, of 5HT1A and 5HT2 receptors as well as the 5HT transporter, all at doses below the threshold for cholinergic hyperstimulation and the resultant systemic toxicity. In contrast, with GD17-20 exposure, the initial effect was augmentation of all three components by low doses of CPF. Sensitivity of these effects declined substantially when exposure was shifted to the postnatal period. We also identified major alterations in 5HT-mediated responses, assessed for the adenylyl cyclase signaling cascade. Although GD9-12 exposure had only minor effects, treatment on GD17-20 elicited supersensitivity to both stimulatory and inhibitory responses mediated by 5HT. Our results indicate that CPF affects 5HT receptors, the presynaptic 5HT transporter, and 5HT-mediated signal transduction during a discrete critical gestational window. These effects are likely to contribute to the noncholinergic component of CPF's developmental neurotoxicity.
Judges support doctors' decision to stop treating dying man
Authors: Owen Dyer
Journal: BMJ (2005)

The relatives of an 86 year old Muslim man with multiple organ failure have lost their legal battle to keep him on life support, after the rejection of their last possible appeal.

The man, who for legal reasons is known only as Mr A, has been in hospital since July. The NHS trust responsible for the hospital, which also cannot be named, won permission from the High Court on 26 July to cease dialysis and to forego attempting resuscitation in the event of respiratory failure. But the trust was told not to act on the decision until the family had had time to appeal.

That …
Substitution bias, rapid saturation, and the use of mtDNA for nematode systematics
Authors: M. S. Blouin, C. A. Yowell, C. H. Courtney, J. B. Dame
Journal: Molecular Biology and Evolution (1998)

Only relatively recently have researchers turned to molecular methods for nematode phylogeny reconstruction. Thus, we lack the extensive literature on evolutionary patterns and phylogenetic usefulness of different DNA regions for nematodes that exists for other taxa. Here, we examine the usefulness of mtDNA for nematode phylogeny reconstruction and provide data that can be used for a priori character weighting or for parameter specification in models of sequence evolution. We estimated the substitution pattern for the mitochondrial ND4 gene from intraspecific comparisons in four species of parasitic nematodes from the family Trichostrongylidae (38-50 sequences per species). The resulting pattern suggests a strong mutational bias toward A and T, and a lower transition/transversion ratio than is typically observed in other taxa. We also present information on the relative rates of substitution at first, second, and third codon positions and on relative rates of saturation of different types of substitutions in comparisons ranging from intraspecific to interordinal. Silent sites saturate extremely quickly, presumably owing to the substitution bias and, perhaps, to an accelerated mutation rate. Results emphasize the importance of using only the most closely related sequences in order to infer patterns of substitution accurately for nematodes or for other taxa having strongly composition-biased DNA. ND4 also shows high amino acid polymorphism at both the intra- and interspecific levels, and in higher level comparisons, there is evidence of saturation at variable amino acid sites. In general, we recommend using mtDNA coding genes only for phylogenetics of relatively closely related nematode species and, even then, using only nonsynonymous substitutions and the more conserved mitochondrial genes (e.g., cytochrome oxidases). On the other hand, the high substitution rate in genes such as ND4 should make them excellent for population genetics studies, identifying cryptic species, and resolving relationships among closely related congeners when other markers show insufficient variation.