tbuckley/cabot-search huggingface dataset:
P159 Peripheral Blood Mononuclear Cells from patients with Idiopathic Pulmonary Arterial Hypertension are Hyporesponsive to Inflammatory stimuli
Authors: LC Price, M Paul-Clark, C Meng, D Shao, JA Mitchell, IM Adcock, SJ Wort
Journal: Thorax (2013)

<h3>Background</h3> Inflammation is a key feature of pulmonary arterial hypertension (PAH); circulating levels of plasma cytokines and chemokines are raised, some of which (including interleukin (IL)-6 and CXCL8) are associated with increased mortality (1). We wished to determine whether it was possible to detect an altered inflammatory phenotype in circulating inflammatory cells from PAH patients compared to controls. <h3>Methods</h3> Following ethical approval, patients with idiopathic PAH and age-matched non-smoking control subjects were selected. Peripheral blood mononuclear cells (PBMC) (10<sup>5</sup> cells) or citrated whole blood (WB) were plated into 96-well plates and treated with E. Coli LPS (0–1µg/ml) (Sigma) or recombinant TNF-a (0–10ng/ml) (R&amp;D systems) for 24h at 37°C. Following centrifugation, plasma was aspirated and samples frozen at -20°c, and IL-6 and CXCL8 ELISAs later performed. Data are mean ± SEM. <h3>Results</h3> All patients had idiopathic PAH (n = 12) (7 in NYHA class III-IV) with 6MWD 370 ± 18m, mPAP 72 ± 5mmHg). All patients were taking advanced PAH therapies but not conventional anti-inflammatory therapies. There was no age difference between patients and controls (n = 9) (36.5 ± 3.7 vs. 36.2 ± 2.7 years, NS). At baseline, release of IL-6 and CXCL8 was higher from PBMC from PAH patients than controls (918.1 ± 280.5 vs. 195.2 ± 64.3 for IL-6 (p &lt; 0.05) and 4203 ± 1354 vs. 1048 ± 288.4 p &lt; 0.05 for CXCL8), although no difference was seen between groups from the whole blood assays. Following stimulation with LPS, however, release of both IL-6 and CXCL8 was lower from both WB and PBMC assays for PAH patients compared to controls. For example for LPS-induced IL-6 release from PBMC, both the maximal effect (E<sub>max</sub>) was lower in PAH vs. controls (5148 ± 1320 vs. 9154 ± 2510 pg/ml, p &lt; 0.05) and the log EC<sub>50</sub> (half maximal effective concentration) was higher in PAH vs. controls (-2.70 ± 0.27 vs. -5.90 ± 1.16 µg/ml, p &lt; 0.01) (Figure 1). Similar results were seen following stimulation with TNF-a. <h3>Conclusion</h3> The main findings of this study are that: (1) baseline CXCL8 and IL6 release was higher from PBMCs of patients with PAH compared to control donors; (2) PBMCs and WB from patients were hyporesponsive to LPS (and TNF-a), suggesting an altered inflammatory phenotype, at least in these models, to these stimuli. <h3>References</h3> Soon E. <i>et al</i>, <i>Circulation</i>. 2010;122(9):920–7
Hyperthermia, still experimental, may win place in cancer therapy
Authors: Roger S. Johnson
Journal: JAMA (1981)

Oncologists and basic researchers at more than 40 universities and cancer centers are developing and testing methods of heating tumors to induce their regression. In one of the more novel of these methods, a patient's blood is heated externally and returned to circulate in his body. This method of hyperthermia, applied to the whole body or regions of it, has been used to treat more than 400 cancer patients. Hundreds more have been treated with various other experimental methods of hyperthermia within the last decade. Its use has increased rapidly in recent years as have reports that it effects tumor regression and prolongs survival in patients whose cancers are less than responsive to conventional therapy. The skepticism with which these reports were received a few years ago has matured to almost acceptance on the part of many oncologists, though hyperthermia has not yet been tested in a randomized study. The
1032-123 Mechanisms for left ventricular outflow tract obstruction after initial septal myectomy for obstructive hypertrophic cardiomyopathy
Authors: Kenji Minakata, Joseph A Dearani, Hartzell V Schaff, Patrick W O'Leary, Steve R Ommen, Gordon K Danieslon
Journal: Journal of the American College of Cardiology (2004)
Brain death and organ donation in a neurosurgical unit: audit of recent practice.
Authors: D Gentleman, J Easton, B Jennett
Journal: BMJ (1990)

To assess the potential for increasing the yield of donors by comparing the current pattern of brain death and organ donation in a neurosurgical unit with that reported in 1981 and with a recent national audit.Retrospective review of all deaths for 1986, 1987, and 1988 and prospective data for 1989.A regional neurosurgical unit serving 2.7 million population.Of 553 deaths, 35% (191) patients died while on a ventilator and 17% (92) after discontinuation of ventilation. Medical contraindications to donation were found in 23% (32) of 141 patients tested for brain death, in 38% (19) of 50 patients who died while being ventilated who were not tested, and in 12% (11) of 92 patients no longer being ventilated. Consent for donation was sought in 88% (96) of 109 medically suitable brain dead patients and granted in 70% (67) of these. Half those with permission for multiorgan donation had only the kidneys removed.More organs may be lost owing to transplant team logistics than by failure to seek consent from relatives of brain dead patients. The estimated size of the pool of potential donors depends on what types of patients might be considered. Ensuring that all who die while being ventilated are tested for brain death and considering the potential for donation before withdrawing ventilation could yield more donors. Ventilating more patients who are hopelessly brain damaged to secure more donors raises ethical and economic issues.
Stimulation of gonadal steroid synthesis by chronic excess of adrenocorticotropin in patients with adrenocortical insufficiency.
Authors: H Vierhapper, P Nowotny, W Waldhäusl
Journal: Journal of Clinical Investigation (1986)

Analysis of 24-h urinary steroid excretion was performed by capillary gas chromatography in six patients (five men, one woman) with adrenocortical insufficiency. Ten healthy subjects (five men, five women) served as controls. A complete absence of all 21-hydroxylated steroid metabolites was seen in patients with adrenocortical insufficiency, whereas the excretion of several steroids lacking hydroxylation in the 21-position (pregnenolone, pregnenetriol, and 11-ketoandrosterone) was markedly increased. In addition, the presence of 11 beta-hydroxyandrosterone was confirmed by mass-spectrometry in the urine of three patients. This pattern of steroid excretion was unchanged in patients with adrenocortical insufficiency, both after stimulation by 1-24 adrenocorticotropin (ACTH) and after short-term (3-d) suppression with dexamethasone. We conclude that patients with adrenocortical insufficiency present a pattern of steroid excretion characterized by the absence of 21-hydroxylated metabolites. In the absence of functional adrenocortical tissue, long-term pathologically elevated concentrations of ACTH apparently stimulate early steps of steroid synthesis, most likely in the gonads. In addition, the presence of 11-hydroxylated steroid metabolites (11-ketoandrosterone, 11 beta-hydroxyandrosterone) in the urine of patients with adrenocortical insufficiency demonstrates that chronic ACTH excess in this disorder may induce some activity of 11 beta-hydroxylase, an enzyme not found in the gonads under physiological conditions.
Cervical osteomyelitis. Infection due to Staphylococcus epidermidis in hemodialysis patients
Authors: M. A. Parker
Journal: JAMA (1978)

VERTEBRAL bodies are frequent sites of pyogenic osteomyelitis in the adult.<sup>1-3</sup>Anatomically, lumbar vertebrae are most commonly involved, followed by thoracic and, rarely, cervical vertebrae. In most series, vertebral osteomyelitis occurs in the setting of urinary tract disease<sup>2,4,5</sup>or intravenous (IV) drug use.<sup>2,3</sup> The preponderant pathogen in pyogenic osteomyelitis is<i>Staphylococcus aureus</i>,<sup>1,2</sup>followed by Gram-negative rods usually from a urinary tract focus.<sup>5</sup><i>Staphylococcus epidermidis</i>is a rare cause of osteomyelitis.<sup>4,5</sup>The first report of osteomyelitis in hemodialysis patients implicated<i>S epidermidis</i>in three of five cases, either as the sole etiologic agent or combined with<i>S aureus</i>or<i>Pseudomonas aeruginosa</i>.<sup>6</sup>We describe two cases of cervical osteomyelitis due to<i>S epidermidis</i>in long-term hemodialysis patients. <h3>Report of Cases</h3><h3>Case 1.—</h3> A 42-year-old man was admitted in February 1976, with complaints of neck and shoulder pains of three days' duration. He had a history
Novel assay for detecting celiac disease–associated autoantibodies in dermatitis herpetiformis using deamidated gliadin-analogous fusion peptides
Authors: Michael Kasperkiewicz, Cornelia Dähnrich, Christian Probst, Lars Komorowski, Winfried Stöcker, Wolfgang Schlumberger, Detlef Zillikens, Christian Rose
Journal: Journal of the American Academy of Dermatology (2011)
Medical History: Arthritis in Saxon and mediaeval skeletons
Authors: J. Rogers, I. Watt, P. Dieppe
Journal: BMJ (1981)

Examination of 400 Saxon, Romano-British, and mediaeval skeletons from seven archaeological excavations in the west of England showed an unexpectedly high incidence of osteoarthritis and osteophytosis. Three skeletons had evidence of an erosive peripheral arthritis—one with probable gout, one probable psoriatic arthropathy, and one with possible rheumatoid arthritis. The pattern and types of rheumatic disease, and the resultant disability, were apparently different. An exuberant form of large joint osteoarthritis was common and rheumatoid arthritis and similar diseases rare.
Characterization of benign cutaneous lymphocytic infiltrates by monoclonal antibodies
Authors: ELISABETH RALFKIAER, G. LANGE WANTZIN, D. Y. MASON, H. STEIN, K. THOMSEN
Journal: British Journal of Dermatology (1984)

Skin biopsies from nine patients with a histological and/or clinical diagnosis of cutaneous lymphocytoma, lymphoplasia or Jessner's lymphocytic infiltrate were examined by immunoenzymatic labelling with a panel of monoclonal antibodies against lymphocytes and accessory cells. Similar cellular constituents were demonstrated in the biopsies from three patients with lymphocytoma, two with lymphoplasia and two with atypical lymphocytes, but a protracted benign clinical course. The infiltrates from these patients consisted of T cells, Langerhans cells, related HLA-DR positive dendritic dermal cells and clusters of polyclonal B cells. In four patients, the B cell clusters contained B cell accessory follicular dendritic cells, and thereby closely resembled the B cell follicles seen in lymphoid organs. The T cells were predominantly T helper/inducer cells and in all patients the T cells expressed HLA-DR. One patient diagnosed as lymphocytoma cutis differed from the other patients by having no detectable B cells. One patient with Jessner's lymphocytic infiltrate differed from the other patients by having a marked relative predominance of T suppressor/cytotoxic cells. These data suggest that cutaneous lymphocytoma and lymphoplasia are basically similar disorders which may be considered to be exaggerated immune responses, whereas Jessner's lymphocytic infiltrate may be a separate entity. Immunological analysis may assist in establishing a definite diagnosis in cases of lymphocytoma or lymphoplasia with atypical cytological features.
Brain damage in dogs immediately following pulsatile and non-pulsatile blood flows in extracorporeal circulation
Authors: J. M. Sanderson, G. Wright, F. W. Sims
Journal: Thorax (1972)

The brains of dogs subjected to total cardiac bypass were examined for early signs of ischaemic nerve cell changes. Diffuse nerve cell changes were found immediately following two- and three-hour non-pulsatile perfusions but not following pulsatile perfusions of the same durations. The nerve cell changes found in the brains were acute cell swelling and early ischaemic cell change. Acute cell swelling was found only in the cerebellar Purkinje cells. Ischaemic cell change was found in several regions of the brain but the cerebral cortex and cerebellar Purkinje cells were most frequently affected. Diffuse nerve cell changes are attributed to non-pulsatile blood flow but some complicating factors are recognized. Focal lesions found in three brains may have been due to embolism by blood cell aggregates and/or gas microbubbles.
The 'House Call' in the Electronic Era
Authors: Charles E. Driscoll
Journal: JAMA (1992)

Medicine has been linked to the telephone since its invention. From 1872 through 1876, Americans Elisha Gray and Alexander Graham Bell raced neck and neck to develop an electrical voice transmission device. On March 10, 1876, Alexander Graham Bell summoned his assistant Thomas Watson over his new "voice line" as Bell was experiencing a minor emergency from spilling acid on his skin. Three years later,<i>Lancet</i>carried a description of what was probably the first over-the-phone diagnosis by a physician who identified a child's croupy cough and provided reassurance to his patient's family.<sup>1</sup>Today it is estimated that between 15% and 25% of primary care contacts take place by phone.<sup>2-4</sup>The final disposition of ambulatory office visits is a planned telephone follow-up in 3.3% of family practice and 8% of internal medicine encounters.<sup>5</sup>What we do in everyday practice has long been in need of studies that
Abstract 4407: Neutralizing monoclonal antibody to periostin (PN) inhibits ovarian tumor metastatic growth in animal models
Authors: Min Zhu, Romaine E. Saxton, Lillian Ramos, David D. Chang, Beth Y. Karlan, Judith C. Gasson, Dennis J. Slamon
Journal: Cancer Research (2010)

Abstract Periostin (PN), an extracellular matrix protein, is reported to be overexpressed in a variety of human cancers and its functions appear to be linked to tumor angiogenesis and metastasis. Our previous results show that engineered PN overexpression promotes ovarian tumor growth and dissemination in vivo. In the present study, we developed a neutralizing monoclonal antibody to PN, named MZ-1, and have investigated its effects on human ovarian tumor cell metastasis and progression. MZ-1 markedly reduced tumor metastatic growth in orthotopic ovarian tumor models derived from two PN-expressing ovarian cancer cell lines A2780 and TOV-112D. These in vivo antitumor effects of MZ-1 were attributed to its specific inhibition of anchorage-independent growth and survival of PN-expressing cells, as well as its neutralization on PN-induced migration. The data suggests that blocking PN expression may be a novel approach for treatment of ovarian cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4407.
Attitudes to Psychiatry in the General Hospital
Authors: J. M. Kellett, A. G. Mezey
Journal: BMJ (1970)

A survey of consultant attitudes to psychiatry in six general hospitals is presented and compared with reported findings in general practitioners and medical students.Psychological factors were accepted as important in a variety of medical conditions. Different specialties differed little in their attitudes to neurotic patients and to psychiatrists, younger consultants tending to be more critical. Consultants had a lower level of neuroticism than the general population and medical students, and physicians were less extraverted than surgeons; these personality factors were not related to expressed attitudes.The results suggest that other specialties accept the role of psychiatry, and its integration into the general hospital is not likely to meet with antagonism.
Refined Mapping of the Renal Failure Rf-3 Quantitative Trait Locus
Authors: Caitlin C. O'Meara, Jozef Lazar, Matthew Hoffman, Carol Moreno, Howard J. Jacob
Journal: Journal of the American Society of Nephrology (2010)

Rf-3, a quantitative trait locus (QTL) on rat chromosome 3, affects the development of CKD in Fawn-Hooded Hypertensive (FHH) rats. This QTL spans 110 Mb and approximately 1400 genes; therefore, narrowing the position of this locus is necessary to elucidate potential candidate genes. Here, we used congenic models and comparative genomics to refine the Rf-3 candidate region. We generated congenic lines carrying smaller intervals (subcongenics) of the Rf-3 region and used these lines to reduce the Rf-3 candidate region by 94% (to 7.1 Mb). We used comparative genomics to identify QTL for both nephropathy and albuminuria in the syntenic region of this interval for both human and mouse. We also used the overlapping homologous regions to reduce the number of likely positional candidate genes to 13 known or predicted genes. By combining congenic models and cross-species studies, we narrowed the list of candidate genes to a level that we could sequence the whole interval to further identify the causative gene in future studies.
Effect of Digitalis on Left Ventricular Response to Atrial Pacing in Patients with Angina.
Authors: Lawrence M. Higgs
Journal: Annals of Internal Medicine (1970)

Meeting Abstracts1 May 1970Effect of Digitalis on Left Ventricular Response to Atrial Pacing in Patients with Angina.Lawrence M. Higgs, M.D., D. Luke Glancy, M.D., F.A.C.P., Kevin P. O'Brien, M.R.C.P., Stephen E. Epstein, M.D.Lawrence M. Higgs, M.D.Search for more papers by this author, D. Luke Glancy, M.D., F.A.C.P.Search for more papers by this author, Kevin P. O'Brien, M.R.C.P.Search for more papers by this author, Stephen E. Epstein, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-72-5-778_4 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe abnormal left ventricular hemodynamics frequently observed during angina have been interpreted as manifestations of transient cardiac failure. This study was done in 11 patients with arteriographically proved coronary disease, but no clinical evidence of failure, to determine if left ventricular hemodynamics during angina induced by graded (10-beat increments/min) atrial pacing could be altered by ouabain and to evaluate the effects of ouabain on the pacing rate necessary to provoke angina. Both before and 30 min after ouabain (0.01 mg/kg) measurements were made at rest, during pacing to angina, and on stopping pacing. Resting left ventricular end-diastolic pressure (LVEDP) averaged... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Bethesda, Md. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byThe exercise apex cardiogram: A clinical test in angina pectoris 1 May 1970Volume 72, Issue 5Page: 778-779KeywordsAnginaHeart failureHemodynamicsStable coronary artery disease Issue Published: 1 May 1970 PDF downloadLoading ...
Allosteric Regulation of Glycogen Synthase Controls Glycogen Synthesis in Muscle
Authors: Michale Bouskila, Roger W. Hunter, Adel F.M. Ibrahim, Lucie Delattre, Mark Peggie, Janna A. van Diepen, Peter J. Voshol, Jørgen Jensen, Kei Sakamoto
Journal: Cell Metabolism (2010)

SummaryGlycogen synthase (GS), a key enzyme in glycogen synthesis, is activated by the allosteric stimulator glucose-6-phosphate (G6P) and by dephosphorylation through inactivation of GS kinase-3 with insulin. The relative importance of these two regulatory mechanisms in controlling GS is not established, mainly due to the complex interplay between multiple phosphorylation sites and allosteric effectors. Here we identify a residue that plays an important role in the allosteric activation of GS by G6P. We generated knockin mice in which wild-type muscle GS was replaced by a mutant that could not be activated by G6P but could still be activated normally by dephosphorylation. We demonstrate that knockin mice expressing the G6P-insensitive mutant display an ∼80% reduced muscle glycogen synthesis by insulin and markedly reduced glycogen levels. Our study provides genetic evidence that allosteric activation of GS is the primary mechanism by which insulin promotes muscle glycogen accumulation in vivo.Graphical abstractGraphical AbstractHighlights► A critical glucose-6-phosphate (G6P) action site on glycogen synthase (GS) identified ► A knockin mouse expressing G6P-insensitive mutant GS generated ► GS knockin mice display dramatically reduced ability to accumulate muscle glycogen ► Insulin promotes glycogen synthesis mainly via allosteric activation of GS by G6P
Coronary Artery Calcification Progression Is Heritable
Authors: Andrea E. Cassidy-Bushrow, Lawrence F. Bielak, Patrick F. Sheedy, Stephen T. Turner, Iftikhar J. Kullo, Xihong Lin, Patricia A. Peyser
Journal: Circulation (2007)

Coronary artery calcification (CAC), a marker of coronary artery atherosclerosis, can be measured accurately and noninvasively with the use of electron beam computed tomography. Serial measures of CAC quantify progression of calcified coronary artery plaque. Little is known about the role of genetic factors in progression of CAC quantity.We quantified the relative contributions of measured risk factors and unmeasured genes to CAC progression measured by 2 electron beam computed tomography examinations an average of 7.3 years apart in 877 asymptomatic white adults (46% men) from 625 families in a community-based sample. After adjustment for baseline risk factors and CAC quantity, the estimated heritability of CAC progression was 0.40 (P<0.001). Baseline risk factors and CAC quantity explained 64% of the variation in CAC progression. Thus, genetic factors explained 14% of the variation [(100-64) x (0.40)] in CAC progression. After adjustment for risk factors, the estimated genetic correlation (pleiotropy) between baseline CAC quantity and CAC progression was 0.80 and was significantly different than 0 (P<0.001) and 1 (P=0.037). The environmental correlation between baseline CAC quantity and CAC progression was 0.42 and was significantly different than 0 (P=0.006).Evidence was found that many but not all genetic factors influencing baseline CAC quantity also influence CAC progression. The identification of common and unique genetic influences on these traits will provide important insights into the genetic architecture of coronary artery atherosclerosis.
The Stimulus Selectivity and Connectivity of Layer Six Principal Cells Reveals Cortical Microcircuits Underlying Visual Processing
Authors: Mateo Vélez-Fort, Charly V. Rousseau, Christian J. Niedworok, Ian R. Wickersham, Ede A. Rancz, Alexander P.Y. Brown, Molly Strom, Troy W. Margrie
Journal: Neuron (2014)

Sensory computations performed in the neocortex involve layer six (L6) cortico-cortical (CC) and cortico-thalamic (CT) signaling pathways. Developing an understanding of the physiological role of these circuits requires dissection of the functional specificity and connectivity of the underlying individual projection neurons. By combining whole-cell recording from identified L6 principal cells in the mouse primary visual cortex (V1) with modified rabies virus-based input mapping, we have determined the sensory response properties and upstream monosynaptic connectivity of cells mediating the CC or CT pathway. We show that CC-projecting cells encompass a broad spectrum of selectivity to stimulus orientation and are predominantly innervated by deep layer V1 neurons. In contrast, CT-projecting cells are ultrasparse firing, exquisitely tuned to orientation and direction information, and receive long-range input from higher cortical areas. This segregation in function and connectivity indicates that L6 microcircuits route specific contextual and stimulus-related information within and outside the cortical network.