tbuckley/cabot-search huggingface dataset:
Aldosterone receptors and the evaluation of plasma mineralocorticoid activity in normal and hypertensive states.
Authors: J D Baxter, M Schambelan, D T Matulich, B J Spindler, A A Taylor, F C Bartter
Journal: Journal of Clinical Investigation (1976)

Aldosterone receptors from rat kidney slices were utilized in a competitive binding technique to analyze the contribution of various steroids to plasma "mineralocorticoid" activity and to assess their possible role in hypertension. To consider simultaneously the plasma binding, steroids were incubated with slices in undiluted plasma; competitor activities for [3H]aldosterone binding were aldosterone, 100%; deoxycorticosterone, 16.2%; cortisol, 0.4%; and 18-hydroxy-deoxy-corticosterone and d18-hydroxy-corticosterone, 0.1%. These steroids were more active in buffer than plasma, suggesting that they bind to plasma and that this reduces their receptor binding. Analysis of the competition data suggests that at normal plasma concentrations, aldosterone occupies the receptors to a major extent, cortisol occupies some of the receptors, and deoxycorticosterone and 8-hydroxydeoxycorticosterone contribute little to receptor occupancy. Two steroids implicated in low-renin essential hypertension, 16beta-hydroxy-dehydro-epiandrosterone and 16-oxoandrostenediol, did not have significant competitor activity. Competitor activity in plasmas from normal subjects taken at 12 noon (upright) was greater than that in those taken at 8 a.m. (supine). Since the 12 noon samples had higher aldosterone and lower cortisol levels than the 8 a.m. samples, the competitor activity under these physiological circumstances reflects aldosterone more than cortisol. The competitor activities of plasmas from patients relative to normal subjects (100+/-12.1%; mean+/-SEM) were: normal renin "essential" hypertension, 117+/-14%; low-renin essential hypertension, 101+/-6.6%; and primary aldosteronism, 176+/-14.3%. Thus a significant increase in activity of steroids that interact with mineralocorticoid receptors was detected in primary aldosteronism (P LESS THAN 0.01) BUT WAS NOT DETECTED IN LOW-RENIN OR NORMAL-RENIN ESSENTIAL HYPERTENSION.
Endocrinology of Woman
Authors: Robert B. Greenblatt
Journal: JAMA (1973)

The preparation of a comprehensive textbook of almost 1,100 large, double-column pages by a sole author (with the exception of two short chapters dealing with chromosomes by Clavero-Nunez) is a stupendous and ambitious task, especially if the work is carefully done, well coded, and excellently written. In this day, books of such magnitude appear only as the cumulative effort of a dozen or more contributors. Professor Botellá-Llusiá, a most prodigious and sagacious man, has given us an encyclopedic account of present-day knowledge of the endocrinology of women. It is a classic, and not since Osler's<i>Principles of Medicine</i>has so all-encompassing a book appeared on the medical scene. The historical references are well chosen, his philosophic approaches brighten its pages, the inclusion of the most recent advances in the field and selection of references—all make for an excellent book that should find a niche in the library of the practicing
Gemcitabine plus Cisplatin versus Gemcitabine plus Carboplatin as First-Line Chemotherapy in Advanced Transitional Cell Carcinoma of the Urothelium: Results of a Randomized Phase 2 Trial
Authors: Luigi Dogliotti, Giacomo Cartenì, Salvatore Siena, Oscar Bertetto, Andrea Martoni, Aldo Bono, Dino Amadori, Haluk Onat, Luca Marini
Journal: European Urology (2007)
Plesiomonas Enteric Infections in the United States
Authors: SCOTT D. HOLMBERG
Journal: Annals of Internal Medicine (1986)

Thirty-one persons nationwide from whom Plesiomonas shigelloides was isolated in large numbers from stool in 1984 were compared with 62 matched control subjects. Infection with P. shigelloides was strongly associated with eating uncooked shellfish, usually raw oysters, in the 48 hours before the onset of illness (p less than 0.00001) and with foreign travel (p less than 0.00006), usually to Mexico. Most ill persons had self-limited diarrhea with blood and mucus in stool and other clinical findings that suggested enteroinvasiveness of infecting organisms. Two patients developed their illnesses after taking ampicillin for reasons unrelated to diarrhea; plesiomonads recovered from their stools were resistant to ampicillin. Seven persons with gastrointestinal complaints had alleviation or resolution of their symptoms after taking antimicrobial agents to which recovered plesiomonads were susceptible. These findings suggest that P. shigelloides may cause enteric disease in the normal host, that it may be acquired from eating uncooked shellfish, and that it may be a cause of travelers' diarrhea.
Surfing the web
Authors: G. Dunea
Journal: BMJ (2002)

Look out, doctors! Your patients may know more than you do. For here is a mere fraction of the 60 pages of medical news that I was able to print out on 21 May in less than 10 minutes by surfing the web. It may not all be peer reviewed or evidence based, but here it is anyway.

In Italy they have a “red cell loader” that attaches drug molecules to erythrocytes and returns them …
A Model for the Evolution of the Mammalian T-cell Receptor / and Loci Based on Evidence from the Duckbill Platypus
Authors: Z. E. Parra, M. Lillie, R. D. Miller
Journal: Molecular Biology and Evolution (2012)

The specific recognition of antigen by T cells is critical to the generation of adaptive immune responses in vertebrates. T cells recognize antigen using a somatically diversified T-cell receptor (TCR). All jawed vertebrates use four TCR chains called α, β, γ, and δ, which are expressed as either a αβ or γδ heterodimer. Nonplacental mammals (monotremes and marsupials) are unusual in that their genomes encode a fifth TCR chain, called TCRµ, whose function is not known but is also somatically diversified like the conventional chains. The origins of TCRµ are also unclear, although it appears distantly related to TCRδ. Recent analysis of avian and amphibian genomes has provided insight into a model for understanding the evolution of the TCRδ genes in tetrapods that was not evident from humans, mice, or other commonly studied placental (eutherian) mammals. An analysis of the genes encoding the TCRδ chains in the duckbill platypus revealed the presence of a highly divergent variable (V) gene, indistinguishable from immunoglobulin heavy (IgH) chain V genes (VH) and related to V genes used in TCRµ. They are expressed as part of TCRδ repertoire (VHδ) and similar to what has been found in frogs and birds. This, however, is the first time a VHδ has been found in a mammal and provides a critical link in reconstructing the evolutionary history of TCRµ. The current structure of TCRδ and TCRµ genes in tetrapods suggests ancient and possibly recurring translocations of gene segments between the IgH and TCRδ genes, as well as translocations of TCRδ genes out of the TCRα/δ locus early in mammals, creating the TCRµ locus.
Symptomatic Neurocutaneous Melanosis in a Child
Authors: Puneet Jain, Lakshminarayanan Kannan, Atin Kumar, Elanthenral Sigamani, Vaishali Suri, Noufal Basheer, Ashish Suri, Sheffali Gulati
Journal: JAMA Neurology (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 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
Functional Divergence in the Arabidopsis -1,3-Glucanase Gene Family Inferred by Phylogenetic Reconstruction of Expression States
Authors: A. C. Doxey, M. W. F. Yaish, B. A. Moffatt, M. Griffith, B. J. McConkey
Journal: Molecular Biology and Evolution (2007)

Plant β-1,3-glucanases (β-1,3-Gs) (E.C. 3.2.1.39) comprise large, highly complex gene families involved in pathogen defense as well as a wide range of normal developmental processes. In spite of previous phylogenetic analyses that classify β-1,3-Gs by sequence relatedness, the functional evolution of β-1,3-Gs remains unclear. Here, expression and phylogenetic analyses have been integrated in order to investigate patterns of functional divergence in the Arabidopsis β-1,3-G gene family. Fifty β-1,3-G genes were grouped into expression classes through clustering of microarray data, and functions were inferred based on knowledge of coexpressed genes and existing literature. The resulting expression classes were mapped as discrete states onto a phylogenetic tree and parsimony reconstruction of ancestral expression states was performed, providing a model of expression divergence. Results showed a highly nonrandom distribution of developmental expression states in the phylogeny (P = 0.0002) indicating a significant degree of coupling between sequence and developmental expression divergence. A weaker, yet significant level of coupling was found using stress response data, but not using hormone-response or pathogen-response data. According to the model of developmental expression divergence, the ancestral function was most likely involved in cell division and/or cell wall remodeling. The associated expression state is widely distributed in the phylogeny, is retained by over 25% of gene family members, and is consistent with the known functions of β-1,3-Gs in distantly related species and gene families. Consistent with previous hypotheses, pathogenesis-related (PR) β-1,3-Gs appear to have evolved from ancestral developmentally regulated β-1,3-Gs, acquiring PR function through a number of evolutionary events: divergence from the ancestral expression state, acquisition of pathogen/stress-responsive expression patterns, and loss of the C-terminal region including the glycosylphosphatidylinisotol (GPI)-anchoring site thus allowing for extracellular secretion.
The Hospice Movement
Authors: Marianne Gideon
Journal: JAMA (1979)

<h3>To the Editor.—</h3> John P. Callan, MD (241:600, 1979), spoke for many of us in his editorial "The Hospice Movement." Our experience has shown that dying persons and their families do experience strong emotions and no doubt have special needs. However, we believe and practice that these needs can be met in general hospitals. It is true that general hospitals are primarily designed to treat and cure acute medical crises. But, there is room for the philosophy of palliation and support in hospitals concerned with a humanistic approach to the care of all of its clients. We believe that the Hospice Services at Albert Einstein Medical Center, Northern Division, can be modeled by other general hospitals to this end. Currently, our program staff consists of two staff counselors, a secretary, volunteers in the home, and myself as director. The counselors, as part of the Hospice Services, see patients, their families,
Randomized Controlled Trials and Comparative Effectiveness Research
Authors: Olwen M. Hahn, Richard L. Schilsky
Journal: Journal of Clinical Oncology (2012)

Comparative effectiveness research (CER) has been promoted as a way to improve the translation gap between clinical research and everyday clinical practice as well as to deliver more cost-effective health care. CER will account for a significant portion of funding allocated by the US government for health care research. Oncology has a rich history of improving clinical outcomes and advancing research through randomized controlled trials (RCTs). In this article, we review the role of RCTs in achieving the goals of CER, with particular emphasis on the role of publicly funded clinical trials.
We cannot afford an AIDS epidemic.
Authors: S Dodwell
Journal: BMJ (1990)

I remember her so well.It was the summer of 1985 and I was a student in the department of medicine.Everyone was baffled-pyrexia and diarrhoea in a wasted young lady with generalised lymphadenopathy.We ran practically every test the laboratory could offer-multiple blood, urine, and stool samples, lumbar punctures, x ray examinations, bone marrow trephines, and aspirates, lymph node biopsy.She suffered in uncomplaining silence.But on going back over her history the fact that her husband was a long distance lorry driver took on a sinister new significance in the light of recent developments in the medical scene in neighbouring countries.A new blood test had become available at our blood
Functional Evolution of an Anthocyanin Pathway Enzyme during a Flower Color Transition
Authors: Stacey D. Smith, Shunqi Wang, Mark D. Rausher
Journal: Molecular Biology and Evolution (2012)

Dissecting the genetic basis for the evolution of species differences requires a combination of phylogenetic and molecular genetic perspectives. By mapping the genetic changes and their phenotypic effects onto the phylogeny, it is possible to distinguish changes that may have been directly responsible for a new character state from those that fine tune the transition. Here, we use phylogenetic and functional methods to trace the evolution of substrate specificity in dihydroflavonol-4-reductase (Dfr), an anthocyanin pathway gene known to be involved in the transition from blue to red flowers in Iochroma. Ancestral state reconstruction indicates that three substitutions occurred during the flower color transition, whereas several additional substitutions followed the transition. Comparisons of enzymatic function between ancestral proteins in blue- and red-flowered lineages and proteins from present-day taxa demonstrate that evolution of specificity for red pigment precursors was caused by the first three substitutions, which were fixed by positive selection and which differ from previously documented mutations affecting specificity. Two inferred substitutions subsequent to the initial flower color transition were also adaptive and resulted in an additional increase in specificity for red precursors. Epistatic interactions among both sets of substitutions may have limited the order of substitutions along branches of the phylogeny leading from blue-pigmented ancestors to the present-day red-flowered taxa. These results suggest that the species differences in DFR specificity may arise by a combination of selection on flower color and selection for improved pathway efficiency but that the exact series of genetic changes resulting in the evolution of specificity is likely to be highly contingent on the starting state.
Faecal metabolite profiling identifies medium-chain fatty acids as discriminating compounds in IBD
Authors: Vicky De Preter, Kathleen Machiels, Marie Joossens, Ingrid Arijs, Christophe Matthys, Severine Vermeire, Paul Rutgeerts, Kristin Verbeke
Journal: Gut (2014)

<h3>Background</h3> Bacteria play a role in the onset and perpetuation of intestinal inflammation in IBD. Compositional alterations may also change the metabolic capacities of the gut bacteria. <h3>Objective</h3> To examine the metabolic activity of the microbiota of patients with Crohn9s disease (CD), UC or pouchitis compared with healthy controls (HC) and determine whether eventual differences might be related to the pathogenesis of the disease. <h3>Methods</h3> Faecal samples were obtained from 40 HC, 83 patients with CD, 68 with UC and 13 with pouchitis. Disease activity was assessed in CD using the Harvey–Bradshaw Index, in UC using the UC Disease Activity Index and in pouchitis using the Pouchitis Disease Activity Index. Metabolite profiles were analysed using gas chromatography–mass spectrometry. <h3>Results</h3> The number of metabolites identified in HC (54) was significantly higher than in patients with CD (44, p&lt;0.001), UC (47, p=0.042) and pouchitis (43, p=0.036). Multivariate discriminant analysis predicted HC, CD, UC and pouchitis group membership with high sensitivity and specificity. The levels of medium-chain fatty acids (MCFAs: pentanoate, hexanoate, heptanoate, octanoate and nonanoate), and of some protein fermentation metabolites, were significantly decreased in patients with CD, UC and pouchitis. Hexanoate levels were inversely correlated to disease activity in CD (correlation coefficient=−0.157, p=0.046), whereas a significant positive correlation was found between styrene levels and disease activity in UC (correlation coefficient=0.338, p=0.001). <h3>Conclusions</h3> Faecal metabolic profiling in patients with IBD relative to healthy controls identified MCFAs as important metabolic biomarkers of disease-related changes. <h3>Trial Registration No:</h3> NCT 01666717.
Invasive pulmonary aspergillosis in non-immunocompromised patients.
Authors: J L Hovenden, F Nicklason, R A Barnes
Journal: BMJ (1991)

Invasive pulmonary aspergillosis can occur in non-immunocompromised patients: consider diagnostic bronchoscopy or open lung biopsy in any patient with progressive pulmonary infiltrates who fails to respond to conventional antimicrobial treatment.
A Retrospective Analysis of Clinical Outcomes of Patients Older Than or Equal to 80 Years with Small Cell Lung Cancer
Authors: Toshiyuki Noguchi, Hideaki Mochizuki, Mariko Yamazaki, Eriko Kawate, Yohei Suzuki, Teruhiko Sato, Hideki Takahashi
Journal: Journal of Thoracic Oncology (2010)
Abstract 1107: Tumor microenvironment based modulation of thyroid cancer phenotype
Authors: Neha Y. Tuli, Jonathan Cabin, Robert Suriano, Robert Bednarczyk, Elyse Hanly, Jan Geliebter, Edward Shin, Raj K. Tiwari
Journal: Cancer Research (2014)

Abstract Inflammation plays a pivotal role in the progression of solid malignant tumor with studies showing that the presence of specific inflammatory-immune cells, such as macrophages, at the tumor site leads to poor prognosis. M1 polarized macrophages secrete pro-inflammatory chemokines and cytokines which induce an epithelial to mesenchymal transition (EMT) in tumor cells; a process where epithelial cells acquire mesenchymal traits, thus facilitating tissue infiltration and consequent metastasis. EMT as a marker of cancer progression is understudied in thyroid cancer. In our present study, we evaluated the crosstalk between the macrophages and the epithelial cells in the thyroid tumor microenvironment with the use of an in vitro model system consisting of an immortalized thyroid cell line (Nthy-ori 3-1), three papillary cancer cell lines (BCPAP, 8505C and TPC-1) and one follicular cancer cell line (CGTHW-1). We observed the halt in proliferation of the thyroid cancer cells as the epithelial cells differentiate into mesenchymal cells under the influence of activated macrophage conditioned media. We also observed a statistically significant (p&amp;lt;0.05) upregulation of migration and invasion of thyroid tumor cells in presence of macrophage conditioned media. Using nuclear and cytoplasmic extracts from the thyroid cancer cell lines, we observed that EMT markers including E-cadherin, β-catenin, vimentin, NFk-B, snail, slug and twist are modulated in response to activated macrophage conditioned media. Downregulation of E-cadherin, required for maintenance of stable junction and β-catenin essential for cell-cell adhesion was noticed in response to macrophage conditioned media. Transcription factors like NFk-B, snail and slug were translocated to the nucleus, which is indicative of the initiation of EMT. Our data provides evidence that macrophage secreted proteins play a crucial role in epithelial-mesenchymal transition in thyroid tumor advancement and metastasis. We have successfully identified some significant markers including transcription factors such as NFk-B, slug, twist and snail that play a critical role in the induction of epithelial to mesenchymal transition in thyroid cancer. These findings will allow for the possible development of targeted therapy designed at inhibiting EMT and subsequent suppression of thyroid cancer metastasis and dissemination. Citation Format: Neha Y. Tuli, Jonathan Cabin, Robert Suriano, Robert Bednarczyk, Elyse Hanly, Jan Geliebter, Edward Shin, Raj K. Tiwari. Tumor microenvironment based modulation of thyroid cancer phenotype. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1107. doi:10.1158/1538-7445.AM2014-1107
Calcium signalling microdomains and the t-tubular system in atrial mycoytes: potential roles in cardiac disease and arrhythmias
Authors: Andrew W. Trafford, Jessica D. Clarke, Mark A. Richards, David A. Eisner, Katharine M. Dibb
Journal: Cardiovascular Research (2013)

The atria contribute 25% to ventricular stroke volume and are the site of the commonest cardiac arrhythmia, atrial fibrillation (AF). The initiation of contraction in the atria is similar to that in the ventricle involving a systolic rise of intracellular Ca(2+) concentration ([Ca(2+)](i)). There are, however, substantial inter-species differences in the way systolic Ca(2+) is regulated in atrial cells. These differences are a consequence of a well-developed and functionally relevant transverse (t)-tubule network in the atria of large mammals, including humans, and its virtual absence in smaller laboratory species such as the rat. Where T-tubules are absent, the systolic Ca(2+) transient results from a 'fire-diffuse-fire' sequential recruitment of Ca(2+) release sites from the cell edge to the centre and hence marked spatiotemporal heterogeneity of systolic Ca(2+). Conversely, the well-developed T-tubule network in large mammals ensures a near synchronous rise of [Ca(2+)](i). In addition to synchronizing the systolic rise of [Ca(2+)](i), the presence of T-tubules in the atria of large mammals, by virtue of localization of the L-type Ca(2+) channels and Na(+)-Ca(2+) exchanger antiporters on the T-tubules, may serve to, respectively, accelerate changes in the amplitude of the systolic Ca(2+) transient during inotropic manoeuvres and lower diastolic [Ca(2+)](i). On the other hand, the presence of T-tubules and hence wider cellular distribution of the Na(+)-Ca(2+) exchanger may predispose the atria of large mammals to Ca(2+)-dependent delayed afterdepolarizations (DADs); this may be a determining factor in why the atria of large mammals spontaneously develop and maintain AF.