tbuckley/cabot-search huggingface dataset:
Pharmacogenetic interactions between angiotensin-converting enzyme inhibitor therapy and the angiotensin-converting enzyme deletion polymorphism in patients with congestive heart failure
Authors: Dennis M. McNamara, Richard Holubkov, Lisa Postava, Karen Janosko, Guy A. MacGowan, Michael Mathier, Srinivas Murali, Arthur M. Feldman, Barry London
Journal: Journal of the American College of Cardiology (2004)
Examination of cutaneous macroglobulinosis by immunoelectron microscopy
Authors: D. LIPSKER, B. CRIBIER, D. SPEHNER, N. BOEHM, E. HEID, E. GROSSHANS
Journal: British Journal of Dermatology (1996)

Cutaneous macroglobulinosis is a rare cutaneous manifestation of Waldenström's disease. Lesions are though to result from accumulation of macroglobulin in the dermis and are therefore called IgM storage papules. Ultrastructural findings in the previously reported cases were contradictory and the nature of the deposits was not established by electron microscopy. The purpose of this study was to analyse such deposits by the use of immunoelectron microscopy. A 60-year-old woman had multiple erythematous papules for 1 year. The histopathological changes consisted of plasmocytic infiltration of the dermis and eosinophilic deposits. The skin changes and other investigations led to a diagnosis of Waldenström's disease. Samples from normal and diseased skin were analysed by electron microscopy and by immunogold labelling with anti-IgM antibodies, after Lowicryl K4M embedding. An extracellular electron dense granular and filamentous material was observed in the mid- and upper dermis, between and within the collagen bundles. No periodicity was noted and no deposits were seen at the dermoepidermal junction. Immunoelectron microscopy showed a positive labelling located only on these deposits, in both normal-appearing skin and in lesions. In this patient, immunoelectron microscopy clearly demonstrated the presence of large amounts of IgM in the dermis, which were found in the lesions of cutaneous macroglobulinosis and in normal skin. These results suggest that the IgM storage papules result from a greater density of deposits rather than a site-specific accumulation.
Circulating hyaluronan in the myelofibrosis/osteomyelosclerosis syndrome and other myeloproliferative disorders
Authors: H. Hasselbalch, P. Junker, I. Lisse, U. Lindqvist, A. Öm Engstr Laurent
Journal: American Journal of Hematology (1991)

Abstract The serum concentration of hyaluronan (HYA) was determined in 59 patients with various myeloproliferative disorders, including 33 patients with idiopathic myelofibrosis. In 18 patients the serum concentration of the aminoterminal propeptide of type III procollagen (PIIINP) was measured concomitantly. Raised serum HYA levels were seen in patients with active disease compared with age‐matched healthy subjects, whereas no significant difference in serum HYA was seen between patients with stable disease and age‐matched controls. Serum HYA concentrations correlated significantly with the leukocyte count (rho = 0.38; P &lt; 0.02) and with the serum concentration of PIIINP (rho = 0.50; P &lt; 0.001). During cytotoxic treatment, the serum HYA and PIIINP concentrations decreased in concert with declining leukocyte counts. These findings suggest that clonal expansion is accompanied by a bone marrow stromal reaction similar to the repair processes following injury to soft connective tissues. The relatively modest changes in serum HYA with frequent overlaps between patient categories and healthy subjects imply that the clinical utility of single determinations of serum HYA in the present disease groups is restrained. On the other hand, sequential measurements of HYA may provide a reflection of the myeloproliferative process in individual patients.
IDENTIFICATION OF A NOVEL CELL TYPE IN PERIPHERAL LYMPHOID ORGANS OF MICE
Authors: Ralph M. Steinman, Zanvil A. Cohn
Journal: The Journal of Experimental Medicine (1974)

Dendritic cells are morphologically distinct cells isolated in vitro from peripheral lymphoid organs of mice. They have a buoyant density of less than 1.082 and can be enriched 7-20-fold by isopycnic centrifugation in albumin columns. Surface adherence of enriched populations may yield cultures containing 50% dendritic cells-preparations which can then be studied in more detail. By functional tests, dendritic cells do not represent morphological variants of either lymphocytes or macrophages. They lack lymphocyte surface differentiation markers and do not exhibit the endocytic capacities of macrophages. In tissue culture, they do not differentiate into macrophages. Dendritic cells have a low labeling index in vitro (1.5-2.5%) following administration of [(3)H]thymidine, and this property distinguishes them from large lymphocytes and promonocytes. Dendritic cells also do not possess the functional properties of other types of reticular cells proposed to exist in lymphoid organs, i.e., they do not synthesize collagen-like macromolecules, they are not stem cells for erythroid and myeloid colony formation, and they do not retain antigens or immune complexes on their cell surface. Dendritic cells thus represent a novel cell type on both functional and morphological grounds.
Low Dietary Folate Initiates Intestinal Tumors in Mice, with Altered Expression of G2-M Checkpoint Regulators <i>Polo-Like Kinase 1</i> and <i>Cell Division Cycle 25c</i>
Authors: Erin Knock, Liyuan Deng, Qing Wu, Daniel Leclerc, Xiao-ling Wang, Rima Rozen
Journal: Cancer Research (2006)

Abstract Clinical reports have suggested that low dietary folate increases risk for colorectal cancer. Animal studies for investigation of folate and tumorigenesis have used carcinogen induction or mice with germ-line mutations. We have developed a new spontaneous tumor model in which mice, with or without a null allele in a key folate-metabolizing enzyme, methylenetetrahydrofolate reductase (Mthfr), develop intestinal tumors due to low dietary folate alone. On folate-deficient diets, 12.5% of Mthfr+/+ mice and 28.1% of Mthfr+/− mice developed tumors; mice on control diets were negative. Dietary and genotype effects on tumor development were significant. To investigate mechanisms of folate-dependent tumorigenesis, we examined levels of DNA damage and gene expression of two genes involved in DNA damage response and G2-M checkpoint regulation, polo-like kinase 1 (Plk1) and cell division cycle 25c (Cdc25c). Folate deficiency increased DNA damage and decreased expression of both genes (assessed by quantitative reverse transcription-PCR and immunofluorescence) in normal intestine compared with levels in mice on control diets. An immunofluorescence assay for CDC25c activity (phosphorylated CDC2) also found CDC25c activity to be decreased in folate-deficient normal intestine. In tumors, however, Plk1 and Cdc25c mRNA were found to be higher (11- and 3-fold, respectively) compared with normal intestine from folate-deficient mice; immunofluorescence studies of PLK1, CDC25c, and phosphorylated CDC2 supported these findings. Our data suggest that folate deficiency can initiate tumor development, that Mthfr mutation can enhance this phenomenon, and that altered expression of Plk1 and Cdc25c may contribute to folate-dependent intestinal tumorigenesis. (Cancer Res 2006; 66(21): 10349-56)
A Handbook of Climatic Treatment, Including Balneology.
Authors: William R. Huggard
Journal: JAMA (1906)

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
Translating Patient‐Oriented Eczema Measure ( <scp>POEM</scp> ) scores into clinical practice by suggesting severity strata derived using anchor‐based methods
Authors: C.R. Charman, A.J. Venn, J.C. Ravenscroft, H.C. Williams
Journal: British Journal of Dermatology (2013)

The Patient-Oriented Eczema Measure (POEM) is a validated, patient-derived assessment measure for monitoring atopic eczema severity, although further information on how different POEM scores translate into disease severity categories is needed for clinical trials, epidemiological research and audit.
Ca <sup>2+</sup> Channel Subtypes and Pharmacology in the Kidney
Authors: Koichi Hayashi, Shu Wakino, Naoki Sugano, Yuri Ozawa, Koichiro Homma, Takao Saruta
Journal: Circulation Research (2007)

A large body of evidence has accrued indicating that voltage-gated Ca(2+) channel subtypes, including L-, T-, N-, and P/Q-type, are present within renal vascular and tubular tissues, and the blockade of these Ca(2+) channels produces diverse actions on renal microcirculation. Because nifedipine acts exclusively on L-type Ca(2+) channels, the observation that nifedipine predominantly dilates afferent arterioles implicates intrarenal heterogeneity in the distribution of L-type Ca(2+) channels and suggests that it potentially causes glomerular hypertension. In contrast, recently developed Ca(2+) channel blockers (CCBs), including mibefradil and efonidipine, exert blocking action on L-type and T-type Ca(2+) channels and elicit vasodilation of afferent and efferent arterioles, which suggests the presence of T-type Ca(2+) channels in both arterioles and the distinct impact on intraglomerular pressure. Recently, aldosterone has been established as an aggravating factor in kidney disease, and T-type Ca(2+) channels mediate aldosterone release as well as its effect on renal efferent arteriolar tone. Furthermore, T-type CCBs are reported to exert inhibitory action on inflammatory process and renin secretion. Similarly, N-type Ca(2+) channels are present in nerve terminals, and the inhibition of neurotransmitter release by N-type CCBs (eg, cilnidipine) elicits dilation of afferent and efferent arterioles and reduces glomerular pressure. Collectively, the kidney is endowed with a variety of Ca(2+) channel subtypes, and the inhibition of these channels by their specific CCBs leads to variable impact on renal microcirculation. Furthermore, multifaceted activity of CCBs on T- and N-type Ca(2+) channels may offer additive benefits through nonhemodynamic mechanisms in the progression of chronic kidney disease.
Efficacy and safety of strontium ranelate in the treatment of knee osteoarthritis: results of a double-blind, randomised placebo-controlled trial
Authors: Jean-Yves Reginster, Janusz Badurski, Nicholas Bellamy, William Bensen, Roland Chapurlat, Xavier Chevalier, Claus Christiansen, Harry Genant, Federico Navarro, Evgeny Nasonov, Philip N Sambrook, Timothy D Spector, Cyrus Cooper
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> Strontium ranelate is currently used for osteoporosis. The international, double-blind, randomised, placebo-controlled Strontium ranelate Efficacy in Knee OsteoarthrItis triAl evaluated its effect on radiological progression of knee osteoarthritis. <h3>Methods</h3> Patients with knee osteoarthritis (Kellgren and Lawrence grade 2 or 3, and joint space width (JSW) 2.5–5 mm) were randomly allocated to strontium ranelate 1 g/day (n=558), 2 g/day (n=566) or placebo (n=559). The primary endpoint was radiographical change in JSW (medial tibiofemoral compartment) over 3 years versus placebo. Secondary endpoints included radiological progression, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and knee pain. The trial is registered (ISRCTN41323372). <h3>Results</h3> The intention-to-treat population included 1371 patients. Treatment with strontium ranelate was associated with smaller degradations in JSW than placebo (1 g/day: −0.23 (SD 0.56) mm; 2 g/day: −0.27 (SD 0.63) mm; placebo: −0.37 (SD 0.59) mm); treatment-placebo differences were 0.14 (SE 0.04), 95% CI 0.05 to 0.23, p&lt;0.001 for 1 g/day and 0.10 (SE 0.04), 95% CI 0.02 to 0.19, p=0.018 for 2 g/day. Fewer radiological progressors were observed with strontium ranelate (p&lt;0.001 and p=0.012 for 1 and 2 g/day). There were greater reductions in total WOMAC score (p=0.045), pain subscore (p=0.028), physical function subscore (p=0.099) and knee pain (p=0.065) with strontium ranelate 2 g/day. Strontium ranelate was well tolerated. <h3>Conclusions</h3> Treatment with strontium ranelate 1 and 2 g/day is associated with a significant effect on structure in patients with knee osteoarthritis, and a beneficial effect on symptoms for strontium ranelate 2 g/day.
S66 Targeting anti-ageing molecule AMPK restores corticosteroid sensitivity in COPD
Authors: AA Azam, PJ Barnes, NM Mercado
Journal: Thorax (2013)

<h3>Rationale</h3> Chronic obstructive pulmonary disease (COPD) is an irreversible inflammatory lung disease and is currently the fourth greatest burden of disease of worldwide. However a key issue is that patients show a lack of response to corticosteroid treatment. Corticosteroid insensitivity is mainly caused by oxidative stress which directly stimulates inflammatory transcription factors and reduces the activity of co-adaptor proteins essential for the inhibitory actions of corticosteroids. AMP-activated kinase (AMPK) is a serine/threonine protein kinase that regulates cellular energy homeostasis and anti-oxidant defences, and has recently been labelled as an anti-ageing molecule. We hypothesised that activation of AMPK using Quercetin reverses corticosteroid resistance caused by cigarette smoke extract (CSE) in a monocytic cell line. <h3>Methods</h3> Human monocytic cell line, U937s, were initially incubated with Quercetin (20µM) for 24 hours and then exposed to CSE for 2 hours. Cells were then treated with dexamethasone (1x10<sup>-11</sup> to 1x10<sup>-6</sup>M) for 45 minutes and stimulated with TNF-a (10ng/ml) for 24 hours. Supernatants were collected and CXCL-8 was measured using ELISA. Corticosteroid resistance was calculated as the ability of dexamethasone to inhibit 25% of TNF-a-induced CXCL-8 (IC<sub>25</sub>). Activation of AMPK by Quercetin was measured using the levels of the phosphorylated AMPK by Western Blot. Nuclear factor erythroid related factor 2 (Nrf-2) levels and glucocorticoid receptor (GR) nuclear translocation were also assessed using Western Blot. <h3>Results</h3> CSE induced corticosteroid resistance in U937s (IC<sub>25</sub> = 30nM vs IC<sub>25</sub> = 5nM). Interestingly Quercetin restored corticosteroid sensitivity by approximately 3 fold (IC<sub>25</sub> = 11nM) compared to CSE. Quercetin increased levels of activated AMPK and also up-regulated the expression of Nrf-2. However, Quercetin was unable to restore GR nuclear translocation. <h3>Conclusions</h3> Quercetin was found to be a potential novel therapy for restoration of corticosteroid sensitivity in COPD. Although the mechanism of action remains to be elucidated, Nrf-2 and AMPK activations which increase anti-oxidant levels and prevents oxidative damage could be a key the mechanism of action Activation of AMPK could therefore be a potential novel mechanism for the restoration of corticosteroid sensitivity and Quercetin could be used as an add-on treatment to corticosteroids in COPD.
The social determinants of asthma
Authors: A. A. Cruz, E. D. Bateman, J. Bousquet
Journal: European Respiratory Journal (2010)

<h3>BACKGROUND AND PURPOSE:</h3> Accurate radiologic prediction of cavernous sinus invasion by pituitary adenoma remains challenging. We aimed to assess whether 1-mm-slice-thickness MRI with deep learning–based reconstruction can better predict cavernous sinus invasion by pituitary adenoma preoperatively and to estimate the depth of invasion and degree of contact in relation to the carotid artery, compared with 3-mm-slice-thickness MRI. <h3>MATERIALS AND METHODS:</h3> This single-institution, prospective study included 67 consecutive patients (mean age, 53 [SD, 12] years; 28 women), between January and August 2020, who underwent a combined contrast-enhanced T1-weighted imaging protocol of 1-mm-slice-thickness MRI + deep learning–based reconstruction and 3-mm-slice-thickness MRI. An expert neuroradiologist who was blinded to the imaging protocol determined cavernous sinus invasion using the modified Knosp classification on 1-mm-slice-thickness MRI + deep learning–based reconstruction and 3-mm-slice-thickness MRI, respectively. Reference standards were established by the consensus of radiologic, intraoperative, pathologic, and laboratory findings. The primary end point was the diagnostic performance of each imaging protocol, and the secondary end points included depth of invasion and degree of contact in relation to the carotid artery. <h3>RESULTS:</h3> The diagnostic performance of 1-mm-slice-thickness MRI + deep learning–based reconstruction (area under the curve, 0.79; 95% CI, 0.69 − 0.89) in predicting cavernous sinus invasion by pituitary adenoma was higher than that of 3-mm-slice-thickness MRI (area under the curve, 0.61; 95% CI, 0.52–0.70; <i>P </i>&lt; .001). One-millimeter-slice-thickness MRI + deep learning–based reconstruction demonstrated greater depth of invasion by pituitary adenomas from the medial intercarotid line than 3-mm-slice-thickness MRI (4.07 versus 3.12 mm, <i>P </i>&lt; .001). A higher proportion of cases were in a greater degree of contact with the intracavernous ICA with 1-mm-slice-thickness MRI + deep learning–based reconstruction than with 3-mm-slice-thickness MRI (total encasement, 37.3% versus 13.4%, <i>P </i>&lt; .001; &gt;270°, 38.8% versus 16.4%, <i>P </i>&lt; .001). <h3>CONCLUSIONS:</h3> Compared with 3-mm-slice-thickness MRI, 1-mm-slice-thickness MRI + deep learning–based reconstruction showed a higher diagnostic performance in preoperatively predicting cavernous sinus invasion by pituitary adenomas and demonstrated a greater depth and degree of contact in relation to the carotid artery.
Interval cancer: nightmare of colonoscopists: Table 1
Authors: Ulrike Haug, Jaroslaw Regula
Journal: Gut (2013)

Colonoscopy has become the number one gastrointestinal endoscopic procedure in the world and is considered the gold standard for detecting colorectal cancer (CRC) and its precursors. For a long time, it was thought to be close to perfect in preventing CRC, implying that the disease does virtually not occur soon after colonoscopy has been performed. However, an increasing body of epidemiological evidence questions this and demonstrates the occurrence of these so-called postcolonoscopy CRCs (PCCRCs) as a kind of interval cancers. The term interval cancer is taken from screening and describes the occurrence of cancer in the time interval between scheduled screening examinations.

Accordingly, colonoscopists fear the nightmare of facing a PCCRC diagnosis in their patients and want to know to which extent these interval cancers are preventable. Two intriguing papers address this question and explore the reasons for CRCs occurring soon after colonoscopy.1 ,2

One study comes from the USA and pooled data from eight prospective colonoscopy studies, for the most part clinical trials with different interventions, which included 9167 patients with adenomas removed at baseline colonoscopy. Overall, 58 CRCs (0.6% of all participants) were identified after a median follow-up of 4 years.1 The second …
Genetically Determined Height and Coronary Artery Disease
Authors: Christopher P. Nelson, Stephen E. Hamby, Danish Saleheen, Jenna C. Hopewell, Lingyao Zeng, Themistocles L. Assimes, Stavroula Kanoni, Christina Willenborg, Stephen Burgess, Phillipe Amouyel, Sonia Anand, Stefan Blankenberg, Bernhard O. Boehm, Robert J. Clarke, Rory Collins, George Dedoussis, Martin Farrall, Paul W. Franks, Leif Groop, Alistair S. Hall, Anders Hamsten, Christian Hengstenberg, G. Kees Hovingh, Erik Ingelsson, Sekar Kathiresan, Frank Kee, Inke R. König, Jaspal Kooner, Terho Lehtimäki, Winifred März, Ruth McPherson, Andres Metspalu, Markku S. Nieminen, Christopher J. O'Donnell, Colin N.A. Palmer, Annette Peters, Markus Perola, Muredach P. Reilly, Samuli Ripatti, Robert Roberts, Veikko Salomaa, Svati H. Shah, Stefan Schreiber, Agneta Siegbahn, Unnur Thorsteinsdottir, Giovani Veronesi, Nicholas Wareham, Cristen J. Willer, Pierre A. Zalloua, Jeanette Erdmann, Panos Deloukas, Hugh Watkins, Heribert Schunkert, John Danesh, John R. Thompson, Nilesh J. Samani
Journal: New England Journal of Medicine (2015)

The nature and underlying mechanisms of an inverse association between adult height and the risk of coronary artery disease (CAD) are unclear.We used a genetic approach to investigate the association between height and CAD, using 180 height-associated genetic variants. We tested the association between a change in genetically determined height of 1 SD (6.5 cm) with the risk of CAD in 65,066 cases and 128,383 controls. Using individual-level genotype data from 18,249 persons, we also examined the risk of CAD associated with the presence of various numbers of height-associated alleles. To identify putative mechanisms, we analyzed whether genetically determined height was associated with known cardiovascular risk factors and performed a pathway analysis of the height-associated genes.We observed a relative increase of 13.5% (95% confidence interval [CI], 5.4 to 22.1; P<0.001) in the risk of CAD per 1-SD decrease in genetically determined height. There was a graded relationship between the presence of an increased number of height-raising variants and a reduced risk of CAD (odds ratio for height quartile 4 versus quartile 1, 0.74; 95% CI, 0.68 to 0.84; P<0.001). Of the 12 risk factors that we studied, we observed significant associations only with levels of low-density lipoprotein cholesterol and triglycerides (accounting for approximately 30% of the association). We identified several overlapping pathways involving genes associated with both development and atherosclerosis.There is a primary association between a genetically determined shorter height and an increased risk of CAD, a link that is partly explained by the association between shorter height and an adverse lipid profile. Shared biologic processes that determine achieved height and the development of atherosclerosis may explain some of the association. (Funded by the British Heart Foundation and others.).