tbuckley/cabot-search huggingface dataset:
Autoimmune Endocrine Disease
Authors: James R. Baker
Journal: JAMA (1997)

Autoimmune endocrine diseases are serious disorders that utilize immense health care resources and cause tremendous disability. They include type 1 diabetes mellitus, thyroiditis, Graves disease, Addison disease, and polyglandular syndromes. Analysis of the basis of autoimmune diseases has been aided by the application of new knowledge in immunologic physiology. Recent investigations using these techniques have revealed complicated disorders that have varied pathogenesis and complex genetic predispositions. While the mainstay of treatment for these diverse diseases remains the replacement of hormones produced by the damaged endocrine organ, investigations into the pathogenesis of these disorders provide hope for the development of specific therapeutic measures to block their pathologic basis.
FDA Statement on Prempro
Authors: Lester M. Crawford, Jr
Journal: JAMA (2002)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Older Mice Intranasally Sensitized with Aspergillus Fumigatus Develop Stronger Eosinophilic Esophageal Inflammation Compared to Their Younger Counterparts
Authors: Antonella Cianferoni, Simona Barni, Cara Smith, Valsamma Abraham, Peng Guan, Francesca Saretta, Katie Ruyman, Hamid Bassiri, Kim E. Nichols, Jonathan M. Spergel
Journal: Journal of Allergy and Clinical Immunology (2014)
A Crohn's disease patient with pustules and fever
Authors: G Bouma, S Neve, N C T van Grieken, C J Mulder, T J Stoof
Journal: Gut (2009)

<h3>Background and Aims</h3> Juvenile systemic lupus erythematosus (SLE) and Kawasaki disease can have several overlapping clinical and laboratory manifestations. But the co-occurrence of both disorders is extremely uncommon. <h3>Methods</h3> To report the case of a young boy who had features of both SLE and KD <h3>Results</h3> A 5 year old boy presented with fever for 2 months associated with photosensitive malar rash, oral ulcers and myalgias.On examination, he was irritable, had malar rash, a generalised erythematosus macular rash, oral ulcers, red and vertically cracked lips, redness of bulbar conjunctiva, cervical lymphadenopathy and hepatomegaly. Laboratory investigations are summarised in Table 1. All infectious disease workup was normal. He had hypocomplementemia, positive ANA, anti dsDNA and anti-nucleosome antibody. He was diagnosed as SLE and initiated on oral prednisolone. Fever subsided, transaminitis and leucopenia showed gradual recovery. One week later developed periungual skin peeling and he remained irritable. Laboratory investigations showed anaemia, thrombocytosis, persistently elevated ESR and high CRP (Table 1) A diagnosis of incomplete KD was proffered. He was given intravenous immunoglobulin (IVIG) (2 gm/kg), which led to prompt improvement in his irritability. He was initiated on aspirin (3 mg/kg/day) and continued on oral prednisolone. Aspirin was discontinued 6 weeks later after confirmation of normal coronary findings on echocardiography. Beau’s lines were noticed in the finger nails at this time. At 3 months follow-up, he continues to remain well. Serum transaminases, platelet counts, ESR and CRP have normalised. (Table 1) <h3>Conclusions</h3> Overlap of KD and SLE is extremely uncommon. (Table 2)
Urokinase-type plasminogen activator is a preferred substrate of the human epithelium serine protease tryptase /PRSS22
Authors: Shinsuke Yasuda, Nasa Morokawa, G. William Wong, Andrea Rossi, Mallur S. Madhusudhan, Andrej Šali, Yuko S. Askew, Roberto Adachi, Gary A. Silverman, Steven A. Krilis, Richard L. Stevens
Journal: Blood (2005)
Results of eVALuate study of hysterectomy techniques: Degree of pain cannot be commented on
Authors: Stephen M F Saunders
Journal: BMJ (2004)

<b>Background and Purpose:</b> Muscle-specific strength training has previously been shown to be effective in the rehabilitation of chronic neck muscle pain in women. The aim of this study was to determine the level of activation of the neck and shoulder muscles using surface electromyography (EMG) during selected strengthening exercises in women undergoing rehabilitation for chronic neck muscle pain (defined as a clinical diagnosis of trapezius myalgia). <b>Subjects:</b> The subjects were 12 female workers (age=30–60 years) with a clinical diagnosis of trapezius myalgia and a mean baseline pain intensity of 5.6 (range=3–8) on a scale of 0 to 9. <b>Method:</b> Electromyographic activity in the trapezius and deltoid muscles was measured during the exercises (lateral raises, upright rows, shrugs, one-arm rows, and reverse flys) and normalized to EMG activity recorded during a maximal voluntary static contraction (MVC). <b>Results:</b> For most exercises, the level of muscle activation was relatively high (&gt;60% of MVC), highlighting the effectiveness and specificity of the respective exercises. For the trapezius muscle, the highest level of muscle activation was found during the shrug (102±11% of MVC), lateral raise (97±6% of MVC), and upright row (85±5% of MVC) exercises, but the latter 2 exercises required smaller training loads (3–10 kg) compared with the shrug exercise (20–30 kg). <b>Discussion and Conclusion:</b> The lateral raise and upright row may be suitable alternatives to shrugs during rehabilitation of chronic neck muscle pain. Several of the strength exercises had high activation of neck and shoulder muscles in women with chronic neck pain. These exercises can be used equally in the attempt to achieve a beneficial treatment effect on chronic neck muscle pain.
MPs urge government to act quickly to strengthen health regulation
Authors: A. O'Dowd
Journal: BMJ (2014)

The government should act quickly to clarify what changes are being planned to the powers held by the various regulators of health professionals and professions allied to medicine, according to MPs.

Changes that will make regulators such as the General Medical Council, Nursing and Midwifery Council (NMC), and the Health and Care Professions Council (HCPC) more effective have been mentioned by the Department of Health, but a timescale or details on how they will be introduced have not been given.

The parliamentary health select committee published a report on 18 June based on its annual accountability hearing with the Health and Care Professions Council,1 which regulates 16 professions, including biomedical scientists, operating …
Central Nervous System Function in Youth With Type 1 Diabetes 12 Years After Disease Onset
Authors: Elisabeth A. Northam, Debbie Rankins, Ashleigh Lin, R. Mark Wellard, Gaby S. Pell, Sue J. Finch, George A. Werther, Fergus J. Cameron
Journal: Diabetes Care (2009)

OBJECTIVE—In this study, we used neurocognitive assessment and neuroimaging to examine brain function in youth with type 1 diabetes studied prospectively from diagnosis. RESEARCH DESIGN AND METHODS—We studied type 1 diabetic (n = 106) and control subjects (n = 75) with no significant group difference on IQ at baseline 12 years previously by using the Wechsler Abbreviated Scale of General Intelligence, magnetic resonance spectroscopy and imaging, and metabolic control data from diagnosis. RESULTS—Type 1 diabetic subjects had lower verbal and full scale IQs than control subjects (both P &amp;lt; 0.05). Type 1 diabetic subjects had lower N-acetylaspartate in frontal lobes and basal ganglia and higher myoinositol and choline in frontal and temporal lobes and basal ganglia than control subjects (all P &amp;lt; 0.05). Type 1 diabetic subjects, relative to control subjects, had decreased gray matter in bilateral thalami and right parahippocampal gyrus and insular cortex. White matter was decreased in bilateral parahippocampi, left temporal lobe, and middle frontal area (all P &amp;lt; 0.0005 uncorrected). T2 in type 1 diabetic subjects was increased in left superior temporal gyrus and decreased in bilateral lentiform nuclei, caudate nuclei and thalami, and right insular area (all P &amp;lt; 0.0005 uncorrected). Early-onset disease predicted lower performance IQ, and hypoglycemia was associated with lower verbal IQ and volume reduction in thalamus; poor metabolic control predicted elevated myoinositol and decreased T2 in thalamus; and older age predicted volume loss and T2 change in basal ganglia. CONCLUSIONS—This study documents brain effects 12 years after diagnosis in a type 1 diabetic sample whose IQ at diagnosis matched that of control subjects. Findings suggest several neuropathological processes including gliosis, demyelination, and altered osmolarity.
Molecular Analysis of Familial Endometrial Carcinoma: A Manifestation of Hereditary Nonpolyposis Colorectal Cancer or a Separate Syndrome?
Authors: Miina Ollikainen, Wael M. Abdel-Rahman, Anu-Liisa Moisio, Annette Lindroos, Reetta Kariola, Irma Järvelä, Minna Pöyhönen, Ralf Butzow, Päivi Peltomäki
Journal: Journal of Clinical Oncology (2005)

Familial clustering of endometrial carcinoma (EC) may occur as part of hereditary nonpolyposis colorectal cancer (HNPCC), a multiorgan cancer syndrome with mismatch repair (MMR) deficiency. Clustering of EC alone, termed as familial site-specific EC, may constitute a separate entity. Because its genetic basis is unknown, our purpose was to characterize such families molecularly.Twenty-three families with site-specific EC were identified among 519 consecutive patients diagnosed with EC during 1986 to 1997. Tumor tissues were examined for MMR protein expression by immunohistochemical (IHC) analysis, and MMR genes pinpointed by IHC changes were screened for germline mutations by exon-by-exon sequencing, multiplex ligation-dependent probe amplification, and direct tests for mutations common in the population.Among 33 ECs from 23 families, MLH1 protein was lost in seven tumors (21%), MSH2 together with MSH6 was lost in four tumors (12%), and MSH6 alone was lost in five tumors (15%). A truncating germline mutation in MSH6 (3261insC) was identified in one family and a likely pathogenic missense mutation in MSH2 (D603N) was identified in another family. Among the original 519 patients, nine (all with colon cancer in the family) were diagnosed with HNPCC at the outset-six with MLH1 and three with MSH2 mutations.Our study gives a minimum overall frequency of 2.1% (11 of 519) for germline MMR defects ascertained through EC in the index patients. The fact that only two of 23 families with site-specific EC (8.7%) had germline mutations in MMR genes suggests another as yet unknown etiology in most families with site-specific EC.
Assessment of variations in control of asthma over time
Authors: C. Combescure, P. Chanez, P. Saint-Pierre, J-P. Daurès, H. Proudhon, P. Godard
Journal: European Respiratory Journal (2003)

Control and severity of asthma are two different but complementary concepts. The severity of asthma could influence the control over time. The aim of this study was to demonstrate this relationship. A total 365 patients with persistent asthma (severity) were enrolled and followed-up prospectively. Data were analysed using a continuous time homogeneous Markov model of the natural history of asthma. Control of asthma was defined according to three health states which were qualified: optimal, suboptimal and unacceptable control (states 1, 2 and 3). Transition forces (denoted λ ij from state i to state j) and transition probabilities between control states were assessed and the results stratified by asthma severity were compared. Models were validated by comparing expected and observed numbers of patients in the different states. Transition probabilities stabilised between 100–250 days and more rapidly in patients with mild-to-moderate asthma. Patients with mild-to-moderate asthma in suboptimal or unacceptable control had a high probability of transition directly to optimal control. Patients with severe asthma had a tendency to remain in unacceptable control. A Markov model is a useful tool to model the control of asthma over time. Severity modified clearly the health states. It could be used to compare the performance of different approaches to asthma management.
Short-chain fatty acids affect cystic fibrosis airway inflammation and bacterial growth
Authors: Peyman Ghorbani, Prisila Santhakumar, Qingda Hu, Pascal Djiadeu, Thomas M.S. Wolever, Nades Palaniyar, Hartmut Grasemann
Journal: European Respiratory Journal (2015)

The hypoxic environment of cystic fibrosis airways allows the persistence of facultative anaerobic bacteria, which can produce short-chain fatty acids (SCFAs) through fermentation. However, the relevance of SCFAs in cystic fibrosis lung disease is unknown. We show that SCFAs are present in sputum samples from cystic fibrosis patients in millimolar concentrations (mean± sem 1.99±0.36 mM). SCFAs positively correlated with sputum neutrophil count and higher SCFAs were predictive for impaired nitric oxide production. We studied the effects of the SCFAs acetate, propionate and butyrate on airway inflammatory responses using epithelial cell lines and primary cell cultures. SCFAs in concentrations present in cystic fibrosis airways (0.5–2.5 mM) affected the release of granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor and interleukin (IL)-6. SCFAs also resulted in higher IL-8 release from stimulated cystic fibrosis transmembrane conductance regulator (CFTR) F508del-mutant compared to wild-type CFTR-corrected bronchial epithelial cells. At 25 mM propionate reduced IL-8 release in control but not primary cystic fibrosis epithelial cells. Low (0.5–2.5 mM) SCFA concentrations increased, while high (25–50 mM) concentrations decreased inducible nitric oxide synthase expression. In addition, SCFAs affected the growth of Pseudomonas aeruginosa in a concentration- and pH-dependent manner. Thus, our data suggest that SCFAs contribute to cystic fibrosis-specific alterations of responses to airway infection and inflammation.
-Endorphin, Met-enkephalin and corresponding opioid receptors within synovium of patients with joint trauma, osteoarthritis and rheumatoid arthritis
Authors: S. A Mousa, R. H Straub, M. Schafer, C. Stein
Journal: Annals of the Rheumatic Diseases (2007)

<b>Objective:</b> Intra-articularly applied opioid agonists or antagonists modulate pain after knee surgery and in chronic arthritis. Therefore, the expression of β-endorphin (END), Met-enkephalin (ENK), and μ and δ opioid receptors (ORs) within synovium of patients with joint trauma (JT), osteoarthritis (OA) and rheumatoid arthritis (RA) were examined. <b>Methods:</b> Synovial samples were subjected to double immunohistochemical analysis of opioid peptides with immune cell markers, and of ORs with the neuronal markers calcitonin gene-related peptide (CGRP) and tyrosine hydroxylase (TH). <b>Results:</b> END and ENK were expressed by macrophage-like (CD68<sup>+</sup>) and fibroblast-like (CD68<sup>−</sup>) cells within synovial lining layers of all disorders. In the sublining layers, END and ENK were mostly expressed by granulocytes in patients with JT, and by macrophages/monocytes, lymphocytes and plasma cells in those with OA and RA. Overall, END- and ENK-immunoreactive (IR) cells were more abundant in patients with RA than in those with OA and JT. ORs were found on nerve fibres and immune cells in all patients. OR-IR nerve fibres were significantly more abundant in patients with RA than in those with OA and JT. μORs and δORs were coexpressed with CGRP but not with TH. <b>Conclusions:</b> Parallel to the severity of inflammation, END and ENK in immune cells and their receptors on sensory nerve terminals are more abundant in patients with RA than in those with JT and OA. These findings are consistent with the notion that, with prolonged and enhanced inflammation, the immune and peripheral nervous systems upregulate sensory nerves expressing ORs and their ligands to counterbalance pain and inflammation.
The Epidemiologic Data on Falls, 1998-2010
Authors: Christine T. Cigolle, Jinkyung Ha, Lillian C. Min, Pearl G. Lee, Tanya R. Gure, Neil B. Alexander, Caroline S. Blaum
Journal: JAMA Internal Medicine (2015)

Thus, although the free flow of information is touted as a means of promoting patient autonomy, the crowded landscape of biased health care information on the Internet creates an environment in which it may be more difficult for patients to make informed health care decisions.An important first step toward ameliorating these risks would be to clearly label hospital websites in a manner that allows patients to identify them as advertisements.More resources are needed to create, and direct patients to, balanced online informational tools.Clinicians should ask patients what they have learned from online medical searches and assist them in forming a complete picture of the risks and benefits of treatment options.Finally, we must focus future attention not only on the content of health care advertising but on its impact.The risk that imbalanced information on US hospital websites may negatively impact patient decision making should be an area of close scrutiny and may provide support for stricter advertising regulations.
Profound Coordinated Alterations of Intratumoral NK Cell Phenotype and Function in Lung Carcinoma
Authors: Sophia Platonova, Julien Cherfils-Vicini, Diane Damotte, Lucile Crozet, Vincent Vieillard, Pierre Validire, Pascale André, Marie-Caroline Dieu-Nosjean, Marco Alifano, Jean-François Régnard, Wolf-Herman Fridman, Catherine Sautès-Fridman, Isabelle Cremer
Journal: Cancer Research (2011)

Abstract Both the innate and adaptive immune systems contribute to tumor immunosurveillance in mice and humans; however, there is a paucity of direct evidence of a role for natural killer (NK) cells in this important process. In this study, we investigated the intratumoral phenotypic profile and functions of NK cells in primary human tumor specimens of non–small cell lung carcinoma (NSCLC). We used in situ methods to quantify and localize NK cells using the NKp46 marker and we characterized their phenotype in blood, tumoral, and nontumoral samples of NSCLC patients. Intratumoral NK cells displayed a profound and coordinated alteration of their phenotype, with a drastic reduction of NK cell receptor expression specifically detected in the tumoral region. According to their altered phenotype, intratumoral NK cells exhibited profound defects in the ability to activate degranulation and IFN-γ production. We found that the presence of NK cells did not impact the clinical outcome of patients with NSCLC. Finally, we showed that tumor cells heterogeneously express ligands for both activating and inhibitory NK receptors. Taken together, our results suggest that the NSCLC tumor microenvironment locally impairs NK cells, rendering them less tumorcidal and thereby supportive to cancer progression. Cancer Res; 71(16); 5412–22. ©2011 AACR.
Characterization of the differentially methylated region of the Impact gene that exhibits Glires-specific imprinting
Authors: Kohji Okamura, Richard F Wintle, Stephen W Scherer
Journal: Genome biology (2008)

Imprinted genes are exclusively expressed from one of the two parental alleles in a parent-of-origin-specific manner. In mammals, nearly 100 genes are documented to be imprinted. To understand the mechanism behind this gene regulation and to identify novel imprinted genes, common features of DNA sequences have been analyzed; however, the general features required for genomic imprinting have not yet been identified, possibly due to variability in underlying molecular mechanisms from locus to locus. We performed a thorough comparative genomic analysis of a single locus, Impact, which is imprinted only in Glires (rodents and lagomorphs). The fact that Glires and primates diverged from each other as recent as 70 million years ago makes comparisons between imprinted and non-imprinted orthologues relatively reliable. In species from the Glires clade, Impact bears a differentially methylated region, whereby the maternal allele is hypermethylated. Analysis of this region demonstrated that imprinting was not associated with the presence of direct tandem repeats nor with CpG dinucleotide density. In contrast, a CpG periodicity of 8 bp was observed in this region in species of the Glires clade compared to those of carnivores, artiodactyls, and primates. We show that tandem repeats are dispensable, establishment of the differentially methylated region does not rely on G+C content and CpG density, and the CpG periodicity of 8 bp is meaningful to the imprinting. This interval has recently been reported to be optimal for de novo methylation by the Dnmt3a-Dnmt3L complex, suggesting its importance in the establishment of imprinting in Impact and other genes.
Tetrahydrobiopterin Improves Endothelium-Dependent Vasodilation in Chronic Smokers
Authors: Thomas Heitzer, Carsten Brockhoff, Bernd Mayer, Ascan Warnholtz, Hanke Mollnau, Simone Henne, Thomas Meinertz, Thomas Münzel
Journal: Circulation Research (2000)

Abstract —Conditions associated with impaired nitric oxide (NO) activity and accelerated atherosclerosis have been shown to be associated with a reduced bioavailability of tetrahydrobiopterin (BH4). We therefore hypothesized that BH4 supplementation may improve endothelial dysfunction of chronic smokers. Forearm blood flow (FBF) responses to the endothelium-dependent vasodilators acetylcholine (ACh; 0.75, 1.5, and 3.0 μg/100 mL tissue/min) or serotonin (5-HT; 0.7, 2.1, and 6.3 ng/100 mL tissue/min), to the inhibitor of endothelial nitric oxide synthase (NOS) N G -monomethyl- l -arginine (L-NMMA; 2, 4, and 8 μmol/min), and to the endothelium-independent vasodilator sodium nitroprusside (SNP; 0.1, 0.3, and 1.0 μg/100 mL tissue/min) were measured by venous occlusion plethysmography in controls and chronic smokers. Drugs were infused into the brachial artery, and FBF was measured before and during concomitant intra-arterial infusion of BH4, tetrahydroneopterin (NH4; another reduced pteridine), or the antioxidant vitamin C (6 and 18 mg/min). In control subjects, BH4 had no effect on FBF in response to ACh, 5-HT, and SNP. In contrast, in chronic smokers, the attenuated FBF responses to ACh and 5-HT were markedly improved by concomitant administration of BH4, whereas the vasodilator responses to SNP were not affected. L-NMMA-induced vasoconstriction was significantly reduced in smokers compared with controls, suggesting impaired basal NO bioactivity. BH4 improved L-NMMA responses in smokers while having no effect on L-NMMA responses in controls. Pretreatment with vitamin C abolished BH4 effects on ACh-dependent vasodilation. In vitro, NH4 scavenged superoxide created by the xanthine/xanthine oxidase reaction equipotent like BH4 but failed to modify ACh-induced changes in FBF in chronic smokers in vivo. These data support the concept that in addition to the free radical burden of cigarette smoke, a dysfunctional NOS III due to BH4 depletion may contribute at least in part to endothelial dysfunction in chronic smokers. The full text of this article is available at http://www.circresaha.org.