tbuckley/cabot-search huggingface dataset:
Calcitonin Gene-Related Peptide (CGRP): A New Target for Migraine
Authors: Andrew F. Russo
Journal: The Annual Review of Pharmacology and Toxicology (2014)

Migraine is a neurological disorder that manifests as a debilitating headache associated with altered sensory perception. The neuropeptide calcitonin gene-related peptide (CGRP) is now firmly established as a key player in migraine. Clinical trials carried out during the past decade have proved that CGRP receptor antagonists are effective for treating migraine, and antibodies to the receptor and CGRP are currently under investigation. Despite this progress in the clinical arena, the mechanisms by which CGRP triggers migraine remain uncertain. This review discusses mechanisms whereby CGRP enhances sensitivity to sensory input at multiple levels in both the periphery and central nervous system. Future studies on epistatic and epigenetic regulators of CGRP actions are expected to shed further light on CGRP actions in migraine. In conclusion, targeting CGRP represents an approachable therapeutic strategy for migraine.
Cutaneous nodular sarcoidosis with granulomatous renal sarcoid
Authors: AILEEN E.M. TAYLOR, JANET M. MARKS
Journal: British Journal of Dermatology (1988)

Journal Article Cutaneous nodular sarcoidosis with granulomatous renal sarcoid Get access AILEEN E.M. TAYLOR, AILEEN E.M. TAYLOR University Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP, U.K. Dr A.Taylor. Search for other works by this author on: Oxford Academic Google Scholar JANET M. MARKS JANET M. MARKS University Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 119, Issue 1, 1 July 1988, Pages 107–109, https://doi.org/10.1111/j.1365-2133.1988.tb07110.x Published: 01 July 1988
Altered leucocyte trafficking and suppressed tumour necrosis factor alpha release from peripheral blood monocytes after intra-articular glucocorticoid treatment
Authors: J. H Steer, D. T S Ma, L. Dusci, G. Garas, K. E Pedersen, D. A Joyce
Journal: Annals of the Rheumatic Diseases (1998)

A generalised transient improvement may follow intra-articular administration of glucocorticoids to patients with inflammatory arthropathy. This may represent a systemic anti-inflammatory effect of glucocorticoid released from the joint, mediated through processes such as altered leucocyte trafficking or suppressed release of pro-inflammatory cytokines. Patients, who had received intra-articular injections of glucocorticoids were therefore studied for evidence of these two systemic effects.Patients with rheumatoid arthritis were studied. Peripheral blood leucocyte counts, tumour necrosis factor alpha (TNF alpha) release by peripheral blood monocytes, blood cortisol concentrations, and blood methylprednisolone concentration were measured for 96 hours after intra-articular injection of methylprednisolone acetate.Measurable concentrations of methylprednisolone were present in blood for up to 96 hours after injection. Significant suppression of the hypothalamic-pituitary-adrenal axis persisted throughout this time. Altered monocyte and lymphocyte trafficking, as evidenced by peripheral blood monocytopenia and lymphopenia, was apparent by four hours after injection and resolved in concordance with the elimination of methylprednisolone. Granulocytosis was observed at 24 and 48 hours. Release of TNF alpha by endotoxin stimulated peripheral blood monocytes was suppressed at four hours and thereafter. Suppression was maximal at eight hours and was largely reversed by the glucocorticoid antagonist, mifepristone.After intra-articular injection of methylprednisolone, blood concentrations of glucocorticoid are sufficient to suppress monocyte TNF alpha release for at least four days and to transiently alter leucocyte trafficking. These effects help to explain the transient systemic response to intra-articular glucocorticoids. Suppression of TNF alpha is principally a direct glucocorticoid effect, rather than a consequence of other methylprednisolone induced changes to blood composition.
Medical Mistrust, Diabetes Self-Management, and Glycemic Control in an Indigent Population With Type 2 Diabetes
Authors: L. E. Egede
Journal: Diabetes Care (2006)

Diabetes is a chronic debilitating condition associated with significant morbidity, mortality, and health care costs (1). Morbidity and mortality are higher in blacks than in whites (1). Medical mistrust by black patients has been hypothesized as a contributory factor (2); however, the evidence is inconclusive (3). The purposes of this study were to determine whether there are racial or ethnic differences in medical mistrust and ascertain the association among medical mistrust, self-management, glycemic control, and health-related quality of life (HRQOL) in an indigent population with type 2 diabetes. We hypothesized that blacks would be less trusting of the medical system and that self-management, glycemic control, and HRQOL would be significantly correlated with medical mistrust in this population.

We used billing records to identify all patients with type 2 diabetes in an indigent clinic of an academic medical center. Patients were contacted by telephone and invited to participate in the study. Over a 12-month period, consenting subjects completed validated surveys to assess trust in the medical care system, diabetes knowledge, diabetes self-management, perceived control of diabetes, and HRQOL. Response rate was 60% and did not differ by race or ethnicity. We only had data on race or ethnicity for responders and nonresponders, and there was no significant difference. Our institutional review board approved the study.

Trust was measured with the 15-item Medical Mistrust Index (MMI) (4). MMI measures distrust …
Asthma-COPD overlap 2015: now we are six
Authors: P. G. Gibson, V. M. McDonald
Journal: Thorax (2015)

<h3>Background</h3> The overlap between asthma and COPD is increasingly recognised. This review examines the new insights, treatment and remaining knowledge gaps for asthma–COPD overlap. <h3>Method</h3> A systematic literature review of cluster analyses of asthma and COPD was performed. Articles from 2009 to the present dealing with prevalence, morbidity and treatment of asthma–COPD overlap were identified and reviewed. <h3>Results</h3> Asthma–COPD overlap was consistently recognised in studies using a variety of different study designs and sampling. The prevalence was approximately 20% in patients with obstructive airways diseases. Asthma–COPD overlap was associated with increased morbidity and possibly an increased mortality and comorbidity. There was evidence of a heterogeneous pattern of airway inflammation that included eosinophilic (in adult asthma), neutrophilic or mixed patterns (in severe asthma and COPD). Systemic inflammation was present in asthma–COPD overlap and resembled that of COPD. Within asthma–COPD overlap, there is evidence of different subgroups, and recognition using bronchodilator responsiveness has not been successful. Guidelines generally recommend a serial approach to assessment, with treatment recommendations dominated by an asthma paradigm. Research is needed into key clinical features that impact outcome, mechanisms and treatment approaches in asthma–COPD overlap. Identifying and treating disease components by multidimensional assessment shows promise. <h3>Conclusions</h3> Asthma–COPD overlap has drawn attention to the significant heterogeneity that exists within obstructive airway diseases. It should be replaced by novel approaches that identify and manage the components of this heterogeneity, such as multidimensional assessment and treatment. Future research is needed to test these novel and personalised approaches.
Purifying Selection Maintains Highly Conserved Noncoding Sequences in Drosophila
Authors: S. Casillas, A. Barbadilla, C. M. Bergman
Journal: Molecular Biology and Evolution (2007)

The majority of metazoan genomes consist of nonprotein-coding regions, although the functional significance of most noncoding DNA sequences remains unknown. Highly conserved noncoding sequences (CNSs) have proven to be reliable indicators of functionally constrained sequences such as cis-regulatory elements and noncoding RNA genes. However, CNSs may arise from nonselective evolutionary processes such as genomic regions with extremely low mutation rates known as mutation "cold spots." Here we combine comparative genomic data from recently completed insect genome projects with population genetic data in Drosophila melanogaster to test predictions of the mutational cold spot model of CNS evolution in the genus Drosophila. We find that point mutations in intronic and intergenic CNSs exhibit a significant reduction in levels of divergence relative to levels of polymorphism, as well as a significant excess of rare derived alleles, compared with either the nonconserved spacer regions between CNSs or with 4-fold silent sites in coding regions. Controlling for the effects of purifying selection, we find no evidence of positive selection acting on Drosophila CNSs, although we do find evidence for the action of recurrent positive selection in the spacer regions between CNSs. We estimate that ∼85% of sites in Drosophila CNSs are under constraint with selection coefficients (Nes) on the order of 10–100, and thus, the estimated strength and number of sites under purifying selection is greater for Drosophila CNSs relative to those in the human genome. These patterns of nonneutral molecular evolution are incompatible with the mutational cold spot hypothesis to explain the existence of CNSs in Drosophila and, coupled with similar findings in mammals, argue against the general likelihood that CNSs are generated by mutational cold spots in any metazoan genome.
Normal Ciliogenesis Requires Synergy between the Cystic Kidney Disease Genes MKS-3 and NPHP-4
Authors: Corey L. Williams, Svetlana V. Masyukova, Bradley K. Yoder
Journal: Journal of the American Society of Nephrology (2010)

Cilia dysfunction contributes to renal cyst formation in multiple human syndromes including nephronophthisis (NPHP), Meckel-Gruber syndrome (MKS), Joubert syndrome (JBTS), and Bardet-Beidl syndrome (BBS). Although genetically heterogeneous, these diseases share several loci that affect cilia and/or basal body proteins, but the functions and interactions of these gene products are incompletely understood. Here, we report that the ciliated sensory neurons (CSNs) of C. elegans express the putative transmembrane protein MKS-3, which localized to the distal end of their dendrites and to the cilium base but not to the cilium itself. Localization of MKS-3 and other known MKS and NPHP proteins partially overlapped. By analyzing mks-3 mutants, we found that ciliogenesis did not require MKS-3; instead, cilia elongated and cilia-mediated chemoreception was abnormal. Genetic analysis indicated that mks-3 functions in a pathway with other mks genes. Furthermore, mks-1 and mks-3 genetically interacted with a separate pathway (involving nphp-1 and nphp-4) to influence proper positioning, orientation, and formation of cilia. Combined disruption of nphp and mks pathways had cell nonautonomous effects on C. elegans sensilla. Taken together, these data demonstrate the importance of mutational load on the presentation and severity of ciliopathies and expand the understanding of the interactions between ciliopathy genes.
Inhibition of Notch2 by Numb/Numblike controls myocardial compaction in the heart
Authors: Jiwen Yang, Sandra Bücker, Benno Jungblut, Thomas Böttger, Yuval Cinnamon, Jan Tchorz, Matthias Müller, Bernhard Bettler, Richard Harvey, Qing-Yuan Sun, Andre Schneider, Thomas Braun
Journal: Cardiovascular Research (2012)

The ventricular wall of the heart is composed of trabeculated and compact layers, which are separated by yet unknown processes during embryonic development. Here, we wanted to explore the role of Notch2 and Numb/Numblike for myocardial trabeculation and compaction. We found that Notch2 activity is specifically down-regulated in the compact layer during cardiac development in the mouse. The biological role of Notch2 down-regulation was investigated by the expression of constitutively active Notch2 in the myocardium of transgenic mice, resulting in hypertrabeculation, reduced compaction, and ventricular septum defects. To disclose the mechanism that inhibited Notch2 activity during the formation of myocardial layers, we analysed potential suppressors of Notch signalling. We unveiled that concomitant but not separate ablation of Numb and Numblike in the developing heart leads to increased Notch2 activity along with hypertrabeculation, reduced compaction, and ventricular septum defects, phenocopying effects gained by overexpression of constitutively active Notch2. Expression profiling revealed a strong up-regulation of Bmp10 in Numb/Numblike mutant hearts, which might also interfere with trabeculation and compaction. This study identified potential novel roles of Numb/Numblike in regulating trabeculation and compaction by inhibiting Notch2 and Bmp10 signalling.
Attitudes toward euthanasia of physician members of the Italian Society for Palliative Care
Authors: G. Di Mola, P. Borsellino, C. Brunelli, M. Gallucci, A. Gamba, M. Lusignani, C. Regazzo, A. Santosuosso, M. Tamburini, F. Toscani
Journal: Annals of Oncology (1996)
Computer Three-Dimensional Reconstruction of the Sinoatrial Node
Authors: H. Dobrzynski, J. Li, J. Tellez, I.D. Greener, V.P. Nikolski, S.E. Wright, S.H. Parson, S.A. Jones, M.K. Lancaster, M. Yamamoto, H. Honjo, Y. Takagishi, I. Kodama, I.R. Efimov, R. Billeter, M.R. Boyett
Journal: Circulation (2005)

There is an effort to build an anatomically and biophysically detailed virtual heart, and, although there are models for the atria and ventricles, there is no model for the sinoatrial node (SAN). For the SAN to show pacemaking and drive atrial muscle, theoretically, there should be a gradient in electrical coupling from the center to the periphery of the SAN and an interdigitation of SAN and atrial cells at the periphery. Any model should include such features. Staining of rabbit SAN preparations for histology, middle neurofilament, atrial natriuretic peptide, and connexin (Cx) 43 revealed multiple cell types within and around the SAN (SAN and atrial cells, fibroblasts, and adipocytes). In contrast to atrial cells, all SAN cells expressed middle neurofilament (but not atrial natriuretic peptide) mRNA and protein. However, 2 distinct SAN cell types were observed: cells in the center (leading pacemaker site) were small, were organized in a mesh, and did not express Cx43. In contrast, cells in the periphery (exit pathway from the SAN) were large, were arranged predominantly in parallel, often expressed Cx43, and were mixed with atrial cells. An approximately 2.5-million-element array model of the SAN and surrounding atrium, incorporating all cell types, was constructed. For the first time, a 3D anatomically detailed mathematical model of the SAN has been constructed, and this shows the presence of a specialized interface between the SAN and atrial muscle.
Nephrotoxic Tubular Damage and Calcium Deposition Following Amphotericin B Therapy
Authors: P T WERTLAKE, W T BUTLER, G J HILL, J P UTZ
Journal: JAMA (1963)

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
An academy of medical educators
Authors: Kieran Walsh
Journal: Journal of the Royal Society of Medicine (2008)

‘There are only two sorts of job always open underthe English social system – domestic service andeducation. However abominable one’s record,though one may be fresh from prison or the lunaticasylum, one can always look after the silver or teachthe young. I had not the right presence for afootman so I chose the latter.’
THE EFFECT OF ACUTE ELEVATION OF THE PLASMA CHLORIDE CONCENTRATION ON THE RENAL EXCRETION OF BICARBONATE DURING ACUTE RESPIRATORY ACIDOSIS 1
Authors: James G. Hilton, Nicholas E. Capeci, George T. Kiss, Oscar R. Kruesi, Vincent V. Glaviano, René Wégria
Journal: Journal of Clinical Investigation (1956)

It has been postulated recently that renal bicarbonate reabsorption is entirely dependent on the exchange of hydrogen ions, derived from the dissociation of carbonic acid within the cells of the renal tubule, for the fixed base of filtered bicarbonate in the tubular urine (1-3). According to this theory, an elevation of the CO2 tension of the extracellular fluid results in an increase in the rate of bicarbonate reabsorption because it leads to an increase in the rate of hydrogen ion
GOODPASTURE'S DISEASE AND ALPORT'S SYNDROMES
Authors: A. Neil Turner, Ph.D., M.R.C.P, Andrew J. Rees, M.Sc., F.R.C.P
Journal: Annual Review of Medicine (1996)

▪ Abstract Goodpasture's, or anti-glomerular basement membrane, disease is an uncommon, usually severe disease caused by autoimmunity to a component of certain basement membranes. Alport's syndrome is an inherited, degenerative disorder that affects specific basement membranes. The two are linked by the involvement of type-IV collagen (basement membrane collagen) in their pathogenesis.
Type I Interferon Sensitizes Lymphocytes to Apoptosis and Reduces Resistance to <i>Listeria</i> Infection
Authors: Javier A. Carrero, Boris Calderon, Emil R. Unanue
Journal: The Journal of Experimental Medicine (2004)

Infection with Listeria monocytogenes causes lymphocyte apoptosis that is mediated by the actions of the pore-forming virulence factor listeriolysin O (LLO). Previous work showed that activated lymphocytes were highly sensitive to LLO-induced apoptosis, whereas resting lymphocytes were less susceptible. We now show that mice deficient in the type I interferon (IFN) receptor were more resistant to Listeria infection and had less apoptotic lesions than wild-type counterparts. Furthermore, treatment of resting splenic lymphocytes with recombinant IFN-alphaA enhanced their susceptibility to LLO-induced apoptosis. Together, these data suggest that type I IFN signaling is detrimental to handling of a bacterial pathogen and may enhance the susceptibility of lymphocytes undergoing apoptosis in response to bacterial pore-forming toxins.
Roquin binds inducible costimulator mRNA and effectors of mRNA decay to induce microRNA-independent post-transcriptional repression
Authors: Elke Glasmacher, Kai P Hoefig, Katharina U Vogel, Nicola Rath, Lirui Du, Christine Wolf, Elisabeth Kremmer, Xiaozhong Wang, Vigo Heissmeyer
Journal: Nature Immunology (2010)
Long-term Efficacy and Safety of Enzalutamide Monotherapy in Hormone-naïve Prostate Cancer: 1- and 2-Year Open-label Follow-up Results
Authors: Bertrand Tombal, Michael Borre, Per Rathenborg, Patrick Werbrouck, Hendrik Van Poppel, Axel Heidenreich, Peter Iversen, Johan Braeckman, Jiri Heracek, Edwina Baskin-Bey, Taoufik Ouatas, Frank Perabo, De Phung, Benoit Baron, Mohammad Hirmand, Matthew R. Smith
Journal: European Urology (2015)

Enzalutamide is an androgen receptor inhibitor with a demonstrated overall survival benefit in metastatic castration-resistant prostate cancer. A phase 2 study of enzalutamide monotherapy in patients with hormone-naïve prostate cancer (HNPC) showed a high response rate for the prespecified primary endpoint (ie, prostate-specific antigen [PSA] response at week 25), regardless of metastases at baseline, and favorable tolerability.To determine the long-term efficacy and safety of enzalutamide monotherapy at 1 and 2 yr.Open-label, single-arm study in patients with HNPC and noncastrate testosterone (≥230 ng/dl).Oral enzalutamide 160mg/d until disease progression or unacceptable toxicity.PSA response (≥80% decline from baseline) assessed at 1 yr (49 wk) and 2 yr (97 wk).The median (range) age was 73 (48-86) yr and 26 patients (39%) presented with metastases at study entry. Of 67 patients enrolled, 45 (67%) remained on enzalutamide at week 97. For patients remaining on therapy, the PSA response rate at week 97 was 100% (95% confidence interval 92-100%). Of 26 patients with metastases at baseline, 13 (50%) had a complete and four (15.4%) had a partial response as best overall tumor response up to 97 wk on treatment. There was overall maintenance of total-body bone mineral density (BMD) and moderate changes in lean and fat body mass at 49 and 97 wk. The most common adverse events were gynecomastia, nipple pain, fatigue, and hot flushes. The study limitations include lack of a control group and of endocrine, glycemic, and lipid data at 97 wk.Long-term enzalutamide monotherapy in men with noncastrate HNPC is associated with large sustained reductions in PSA, signals indicating a favorable tumor response, and favorable safety/tolerability profile, with relatively small negative effects on total-body BMD.In this long-term follow-up of the efficacy and safety of enzalutamide monotherapy in patients with hormone-naïve prostate cancer, enzalutamide maintained long-term reductions in prostate-specific antigen, with a minimal impact on total-body bone mineral density.NCT01302041.
Oxidized Low-Density Lipoprotein Autoantibodies, Chronic Infections, and Carotid Atherosclerosis in a Population-Based Study
Authors: Manuel Mayr, Stefan Kiechl, Sotirios Tsimikas, Elizabeth Miller, Joanna Sheldon, Johann Willeit, Joseph L. Witztum, Qingbo Xu
Journal: Journal of the American College of Cardiology (2006)