tbuckley/cabot-search huggingface dataset:
Hyperglycemia Inhibits Vascular Smooth Muscle Cell Apoptosis Through a Protein Kinase C–Dependent Pathway
Authors: Jennifer L. Hall, Christian M. Matter, Xiaohong Wang, Gary H. Gibbons
Journal: Circulation Research (2000)

We hypothesized that the pathogenesis of diabetic vasculopathy involves the abnormal regulation of vascular smooth muscle cell (VSMC) apoptosis. In nondiabetic mice, a reduction in carotid artery blood flow resulted in a significant loss of medial VSMCs via apoptosis (normal flow 84+/-1 viable VSMCs, reduced flow 70+/-5 viable VSMCs; n=12, P:<0.01). In contrast, flow-induced VSMC apoptosis was markedly attenuated in streptozotocin-induced diabetic mice (normal flow 85+/-2 viable VSMC, reduced flow 82+/-4 viable VSMC; n=13, NS). In accord with our in vivo findings, the exposure of cultured rat and human VSMCs to high glucose (17.5 mmol/L) significantly attenuated the induction of apoptosis in response to serum withdrawal (rat VSMCs in normal [5.5 mmol/L] glucose 28+/-1%, high D-glucose 19+/-2%; P:<0.0001). High glucose also inhibited apoptosis induced by Fas ligand (100 ng/mL) (normal 23+/-2%, high D-glucose 13+/-2%; P:<0.006). Supplementation with the nonmetabolized enantiomer L-glucose had no effect. We confirmed reports that high glucose activates protein kinase C (PKC) and demonstrated that PKC blockade with long-term phorbol ester treatment or calphostin C prevented the antiapoptotic effect (P:<0. 001). Moreover, the upregulation of either PKCalpha or PKCbetaII expression was sufficient to inhibit serum withdrawal-induced apoptosis (control 25+/-2%, PKCalpha 11+/-2%, PKCbetaII 8+/-2%; P:<0. 0001), whereas the upregulation of PKCdelta had no significant effect. Taken together, these findings demonstrate that hyperglycemia inhibits VSMC apoptosis via a PKC-dependent pathway.
Physical Activity and Structured Exercise for Patients With Stable Ischemic Heart Disease
Authors: William E. Boden, Barry A. Franklin, Nanette K. Wenger
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Biomarkers and community-acquired pneumonia
Authors: J. S Brown
Journal: Thorax (2009)

<h3>Background</h3> Social support is associated with better health. However, only a limited number of studies have examined the association of social support with health from the adult life course perspective and whether this association is bidirectional. <h3>Methods</h3> Participants (n=6797; 30% women; age range from 40 to 77 years) who were followed from 1989 (phase 2) to 2006 (phase 8) were selected from the ongoing Whitehall II Study. Structural and functional social support was measured at follow-up phases 2, 5 and 7. Mental and physical health was measured at five consecutive follow-up phases (3–8). <h3>Results</h3> Social support predicted better mental health, and certain functional aspects of social support, such as higher practical support and higher levels of negative aspects in social relationships, predicted poorer physical health. The association between negative aspects of close relationships and physical health was found to strengthen over the adult life course. In women, the association between marital status and mental health weakened until the age of approximately 60 years. Better mental and physical health was associated with higher future social support. <h3>Conclusions</h3> The strength of the association between social support and health may vary over the adult life course. The association with health seems to be bidirectional.
Complex Carbohydrates Are Not Removed During Processing of Glycoproteins by Dendritic Cells
Authors: Anda M. Vlad, Stefan Muller, Mare Cudic, Hans Paulsen, Laszlo Otvos, Franz-Georg Hanisch, Olivera J. Finn
Journal: The Journal of Experimental Medicine (2002)

In contrast to protein antigens, processing of glycoproteins by dendritic cells (DCs) for presentation to T cells has not been well studied. We developed mouse T cell hybridomas to study processing and presentation of the tumor antigen MUC1 as a model glycoprotein. MUC1 is expressed on the surface as well as secreted by human adenocarcinomas. Circulating soluble MUC1 is available for uptake, processing, and presentation by DCs in vivo and better understanding of how that process functions in the case of glycosylated antigens may shed light on antitumor immune responses that could be initiated against this glycoprotein. We show that DCs endocytose MUC1 glycopeptides, transport them to acidic compartments, process them into smaller peptides, and present them on major histocompatability complex (MHC) class II molecules without removing the carbohydrates. Glycopeptides that are presented on DCs are recognized by T cells. This suggests that a much broader repertoire of T cells could be elicited against MUC1 and other glycoproteins than expected based only on their peptide sequences.
SLEEP AND AROUSAL: Thalamocortical Mechanisms
Authors: David A. McCormick, Thierry Bal
Journal: Annual Review of Neuroscience (1997)

▪ Abstract Thalamocortical activity exhibits two distinct states: (a) synchronized rhythmic activity in the form of delta, spindle, and other slow waves during EEG-synchronized sleep and (b) tonic activity during waking and rapid-eye-movement sleep. Spindle waves are generated largely through a cyclical interaction between thalamocortical and thalamic reticular neurons involving both the intrinsic membrane properties of these cells and their anatomical interconnections. Specific alterations in the interactions between these cells can result in the generation of paroxysmal events resembling absence seizures in children. The release of several different neurotransmitters from the brain stem, hypothalamus, basal forebrain, and cerebral cortex results in a depolarization of thalamocortical and thalamic reticular neurons and an enhanced excitability in many cortical pyramidal cells, thereby suppressing the generation of sleep rhythms and promoting a state that is conducive to sensory processing and cognition.
Instructional Set and Physiological Response to CO<sub>2</sub> Inhalation
Authors: Lawrence A. Welkowitz, Laszlo Papp, Jose Martinez, Susan Browne, Jack M. Gorman
Journal: American Journal of Psychiatry (1999)

OBJECTIVE: Previous studies have suggested that manipulations in patient instructions before inhalation of carbon dioxide (CO2) may blunt its anxiogenic effects. The authors examined the effects of a range of instructional types on panic rates and physiological responses to CO2 inhalation. METHOD: Thirty-seven patients with panic disorder and 16 normal subjects were exposed to CO2 inhalation under one of three instructional conditions: 1) reassurance (reiterated safety assurances), 2) control dial (patients were instructed on using an operative dial to reduce the concentration of CO2 in the breathing canopy), and 3) basic instructions (standard information). Perceived breathlessness was measured with the Borg Scale of Respiratory Exertion. RESULTS: Manipulation of instructional sets did not affect panic rates among patients. The reassurance condition, however, produced a significant reduction in perceived breathlessness. CONCLUSIONS: CO2-induced panic is a robust biological effect that occurs independent of cognitive set changes, such as illusion of control or reassurance of safety. Conclusions drawn from this study are bolstered by the fact that it is methodologically rigorous: it had a large number of subjects, used random assignment to one of three instructions, included a full array of both subjective and biological measures, and included independent ratings.
IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction
Authors: Taro Kawai, Ken Takahashi, Shintaro Sato, Cevayir Coban, Himanshu Kumar, Hiroki Kato, Ken J Ishii, Osamu Takeuchi, Shizuo Akira
Journal: Nature Immunology (2005)
The Muir-Torre syndrome: A 25-year retrospect
Authors: Robert A Schwartz, Douglas P Torre
Journal: Journal of the American Academy of Dermatology (1995)

The Torre or Muir-Torre syndrome consists of certain types of sebaceous neoplasms of the skin, with or without keratoacanthomas, and one or more low-grade visceral malignancies in the absence of other predisposing factors. The sebaceous tumors are relatively uncommon or rare: sebaceous adenoma, sebaceous epithelioma, basal cell epithelioma with sebaceous differentiation, and sebaceous carcinoma. Sebaceous hyperplasia and hamartomas such as nevus sebaceus of Jadassohn, with or without a sebaceous epithelioma within it, are not a defining part of this syndrome. Sebaceous hyperplasia is common in elderly light-complexioned people with or without this syndrome. Nevus sebaceus of Jadassohn is not rare and is predisposed to the development of other neoplasms within it, including occasionally a sebaceous epithelioma. Colonic polyps are frequently present. Muir-Torre syndrome requires recognition because affected patients are at risk of multiple primary malignancies. The skin lesions may be the first sign of this syndrome, although more often its cutaneous signs follow the diagnosis of at least the first visceral malignancy. The Muir-Torre syndrome portends the greater possibility of a favorable prognosis than might be anticipated otherwise because the visceral cancers are usually low-grade malignancies. However, they are often multiple, so identifying such patients will affect their management in a few ways. Because these indolent visceral malignancies tend to permit prolonged survival, even metastatic disease may respond well to aggressive surgical treatment. The sebaceous cancers in this syndrome, like the visceral malignancies, are less aggressive than their counterparts unassociated with this syndrome. Because this syndrome is inherited in an autosomal dominant manner, identifying one patient means delineating an entire family, which should be investigated. This syndrome may be caused by a defective mismatch DNA repair gene.
FGF9-induced proliferative response to eosinophilic inflammation in oesophagitis
Authors: D J Mulder, I Pacheco, D J Hurlbut, N Mak, G T Furuta, R J MacLeod, C J Justinich
Journal: Gut (2008)

<h3>Background:</h3> Oesophagitis is characterised by basal cell hyperplasia and activated eosinophils, which release mediators including major basic protein (MBP). MBP and its mimetic polyarginine activate the calcium sensing receptor (CaSR) on oesophageal epithelium. Fibroblast growth factor 9 (FGF9) is implicated in epithelial homeostasis and proliferative response to injury, but has not been characterised in the oesophagus. <h3>Objective:</h3> To characterise FGF9 in oesophageal epithelium and oesophagitis, as the result of MBP activation of the CaSR. <h3>Methods:</h3> Human oesophageal epithelial cells (HET-1A) were used to compare affects of calcium, polyarginine and MBP-peptide on FGF9. HET-1A were transfected with interfering RNA (siRNA<sup>CaSR</sup>). FGF9, FGF receptors 2 and 3, bone morphogenetic protein (BMP)-2, BMP-4 and noggin mRNA expression were detected by reverse transcriptase polymerase chain reaction. FGF9 was measured from HET-1A and from normal, gastro-oesophageal reflux and eosinophilic oesophagitis (EoE) patient biopsies using ELISA and immunohistochemistry. HET-1A proliferation was studied using bromodeoxyuridine and MTT. <h3>Results:</h3> FGF9 was secreted by HET-1A cells treated with polyarginine and MBP-peptide, but not calcium. This effect was abrogated by siRNA<sup>CaSR</sup>. FGF9 receptor mRNA was present. HET-1A cells proliferated following rhFGF9, but not MBP-peptide treatment, and rhFGF9 altered transcription of downstream proliferation-related genes (noggin, BMP-2 and BMP-4). FGF9 was increased in biopsies from patients with eosinophilic oesophagitis, which correlated with basal hyperplasia. <h3>Conclusion:</h3> Eosinophil-released MBP acts on the CaSR to increase FGF9 in oesophageal epithelial cells, leading to proliferation. Increased FGF9 is found in biopsies of EoE patients and may play a role in the pathogenesis of oesophagitis.
Interference of glycogenolysis with glycolysis in pancreatic islets from glucose-infused rats.
Authors: W J Malaisse, C Maggetto, V Leclercq-Meyer, A Sener
Journal: Journal of Clinical Investigation (1993)

When pancreatic islets isolated from rats infused for 48-72 h with a hypertonic solution of D-glucose were incubated for two successive periods of 10 min each, in the presence first of 16.7 mM and then 2.8 mM D-[U-14C]glucose, the total output of L-lactic acid during the second incubation was as high as that recorded during the first incubation, while the specific radioactivity of L-lactic acid dramatically decreased during the second incubation. In islets from normoglycemic rats, however, the total output of L-lactic acid decreased and its specific radioactivity modestly increased as the concentration of D-glucose was lowered from 16.7 to 2.8 mM. Such contrasting results indicate that in the glycogen-rich islets isolated from glucose-infused rats, the fall in extracellular D-glucose concentration was not accompanied by a parallel fall in glycolytic flux, the decreased utilization of exogenous D-[U-14C]glucose coinciding with stimulation of glycogenolysis. This unusual metabolic situation also coincided with a transient and paradoxical stimulation of insulin release in response to the decrease in extracellular D-glucose concentration. It is proposed, therefore, that the interference of glycogenolysis with glycolysis in pancreatic islets from glucose-infused rats participates in the paradoxical changes in insulin output which represent a typical feature of B-cell glucotoxicity.
Human monocyte-endothelial cell interaction induces platelet-derived growth factor expression
Authors: Hiroshi Funayama, Uichi Ikeda, Masafumi Takahashi, Youichi Sakata, Sei-Ichi Kitagawa, Yu-Ichi Takahashi, Jun-Ichi Masuyama, Yusuke Furukawa, Yasusada Miura, Shogo Kano, Michio Matsuda, Kazuyuki Shimada
Journal: Cardiovascular Research (1998)

Objective: The purpose of this study was to investigate whether the synthesis of platelet-derived growth factor (PDGF), a major mitogen and chemoattractant for vascular smooth muscle cells, was induced by the direct cell-to-cell interaction between human monocytes and umbilical vein endothelial cells (ECs). Methods: PDGF protein and mRNA expression were determined by cellular ELISA, immunohistochemical and Northern blot analyses. Results: Coculture of monocytes and ECs secreted a large amount of PDGF into the supernatant, whereas culture of ECs or monocytes alone induced low levels of PDGF production. In Northern blot analysis, substantial amounts of PDGF-A and -B mRNA were induced by coculture of monocytes with ECs. Immunohistochemistry revealed that PDGF-B chain protein was detectable in both ECs and monocytes. PDGF production by ECs induced by conditioned medium of the coculture was significantly inhibited by Abs against interleukin-1β (IL-1β) and tumor necrosis factor-α (TNFα). Conclusions: These results indicate that the direct cell-to-cell interaction between human monocytes and ECs induces PDGF synthesis in both types of cells, suggesting that PDGF produced locally by monocyte-EC adhesive interaction plays an important role in the pathogenesis of atherosclerosis by promoting the migration and accumulation of vascular smooth muscle cells.
CONTRIBUTIONS TO THE BIOLOGY OF TISSUE CELLS
Authors: Albert Fischer
Journal: The Journal of Experimental Medicine (1923)

1. A method has been described by which it is possible to scatter isolated tissue cells in a suitable medium. 2. Experiments were undertaken to determine whether minute fragments of fibroblastic culture are able to persist and multiply when transferred into a new culture medium. 3. Cell divisions were not observed in isolated cells under the conditions of the experiment. Growth took place only when the tissue cells were numerous and close to one another.
P162 When Do Patients with Known Lung Cancer Present to Emergency Services?
Authors: P Joshi, MPR Berry, F Bowen
Journal: Thorax (2012)

<h3>Introduction</h3> Use of electronic patient alerts systems are encouraged by government initiatives, especially within the realms of oncology, as a way of expediting relevant clinical review of oncology patients. When a known cancer patient attends an emergency unit, an electronic alert advises selected clinical team members of the attendance, to allow rapid assessment and appropriate management in line with patient’s stage of malignancy. <h3>Methods</h3> Retrospective data captured by the electronic patient alert system was analysed. Data was from three hospital sites within the same trust, which are together form a tertiary referral centre. Data from March 2010 till April 2012 was included. <h3>Results</h3> There were 15,625 cancer attendances in total over the time period, 1,684 were for patients with lung cancer (10.8%). There was no detectable seasonal variation in any cancer group. 1341 of the total cancer admissions occurred during weekdays, averaging 268 patients per named day (12–17% each day) with a fall to approximately 10% at weekends (166 and 177 on Saturdays and Sundays respectively). Overall for lung cancer, 46% (781/1684) of emergency admissions are in-hours (defined Monday to Friday, 9am to 5pm), compared to 42% (6619/15625) of all cancer presentations. Over the whole week, 13% (217/1684) of lung cancer patients arrived before 9am (between midnight and 9am), and 30% (509/1684) arrive after 5 (between 5pm and midnight). Approximately a quarter (24%= 410/1684) of emergency lung cancer attendances occurred between 5pm on Friday and 9am on Monday. Conclusion. This information would indicate that a substantial proportion of unscheduled lung cancer work occurs out-of-hours. To optimise patient care and prevent attendances there may be justification for exploring alternative ways of working to improve cover in late afternoon and early evening when there is increased patient attendance so that these alerts can be received and acted upon rapidly. These data suggest that increased community support is needed especially at weekends.
Mineralocorticoid Receptor Blocker Increases Angiotensin-Converting Enzyme 2 Activity in Congestive Heart Failure Patients
Authors: Shlomo Keidar, Aviva Gamliel-Lazarovich, Marielle Kaplan, Elsa Pavlotzky, Shadi Hamoud, Tony Hayek, Rachel Karry, Zaid Abassi
Journal: Circulation Research (2005)

Aldosterone plays an important role in the pathophysiology of congestive heart failure (CHF), and spironolactone improves cardiovascular function and survival rates in patients with CHF. We hypothesized that the mineralocorticoid receptor blockade (MRB) exerted its beneficial effects by reducing oxidative stress and changing the balance between the counter-acting enzymes angiotensin-converting enzyme (ACE) and ACE2. Monocyte-derived macrophages were obtained from 10 patients with CHF before and after 1 month of treatment with spironolactone (25 mg/d). Spironolactone therapy significantly (P<0.005) reduced oxidative stress, as expressed by reduced lipid peroxide content, superoxide ion release, and low-density lipoprotein oxidation by 28%, 53%, and 70%, respectively. Although spironolactone significantly (P<0.01) reduced macrophage ACE activity by 47% and mRNA expression by 53%, ACE2 activity and mRNA expression increased by 300% and 654%, respectively. In mice treated for 2 weeks with eplerenone (200 mg.kg(-1).d(-1)), cardiac ACE2 activity significantly (P<0.05) increased by 2-fold and was paralleled by increased ACE2 activity in macrophages. The mechanism of aldosterone antagonist action was studied in mouse peritoneal macrophages (MPMs) in vitro. Although ACE activity and mRNA were significantly increased by 250 nmol/L aldosterone, ACE2 was significantly reduced. Cotreatment with eplerenone (2 micromol/L) attenuated these effects. In MPM obtained from p47 knockout mice, where NADPH oxidase is inactive, as well as in control MPMs treated with NADPH oxidase inhibitor, aldosterone did not increase ACE or decrease ACE2. MRB reduced oxidative stress, decreased ACE activity, and increased ACE2 activity, suggesting a protective role for MRB by possibly increasing generation of angiotensin (1-7) and decreasing formation of angiotensin II. These effects are mediated, at least in part, by NADPH oxidase.
Risk assessment in asthma and COPD: a potential role for biomarkers?
Authors: D R Taylor
Journal: Thorax (2009)

There is an increasing literature on the pathological and clinical significance of “inflammatory” biomarkers in asthma and chronic obstructive pulmonary disease (COPD). Their potential role includes risk assessment, but this is somewhat different for the two conditions. In asthma the aim is to identify future risk of poor asthma control or exacerbations. Although induced sputum eosinophils and exhaled nitric oxide are the most widely investigated candidates for use in the clinical arena, there is scope for a great deal of improvement in their application and other biomarkers may prove to be better. For COPD, risk assessment is somewhat different. There is the potential to use biomarkers such as C-reactive protein, fibrinogen or interleukin 6, along with other conventional demographic and physiological measurements, to assess longer term risk of decline in lung function, hospitalisations and mortality. The well-tried model used in cardiovascular disease to assess absolute risk might possibly be adapted for use in COPD, and this should be actively explored.